Description:FORM 2

THE PATENTS ACT 1970
(SECTION 39 OF 1970)
&
THE PATENT RULES, 2003

COMPLETE SPECIFICATION
(SECTION 10)

PHARMACEUTICAL COMPOSITION OF EXTENDED-RELEASE ORAL SUSPENSION AND PROCESS FOR PREPARATION THEREOF

We, LYRUS LIFE SCIENCES PVT LTD,
a company incorporated under the companies act, 1956 having
address at # 54A & 54B [Part], KIDAB Industrial Area, Hoskote,
Bangalore Rural – 562 114, Karnataka, India.
&
NOKHA TRADING LLP
a company incorporated under the companies act, 1956 having
address at No. 22, 7th Cross, Jaibharath Nagar,
Bangalore-560033, Karnataka, India.

The following specification particularly describes the invention and the manner in which it is to be performed:
This application is a Patent of Addition to the Indian Patent Application No. 202247040399 filed on July 14, 2022 which is incorporated for reference.
FIELD OF INVENTION
The present invention relates to an extended-release suspension composition.
The present invention specifically relates to an extended-release suspension composition comprising active ingredients and pharmaceutically acceptable excipients, wherein said composition is in the form of powder for suspension or a ready to use suspension.
The present invention specifically relates to an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts as first active ingredient and second active ingredient selected from anti-histamine and decongestant.
The present invention specifically relates to an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts as first active ingredient and second and third active ingredient selected from anti-histamine and decongestant.
The present invention specifically relates to an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts and Chlorpheniramine or its pharmaceutically acceptable salts and pharmaceutically acceptable excipients.
The present invention specifically relates to an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts and Phenylephrine or its pharmaceutically acceptable salts and pharmaceutically acceptable excipients.
The present invention specifically relates to an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts, Chlorpheniramine or its pharmaceutically acceptable salts, Phenylephrine or its pharmaceutically acceptable salts and pharmaceutically acceptable excipients.
The present invention also relates to a process for the preparation of an extended-release suspension composition.

BACKGROUND OF INVENTION
Extended release solid compositions can be in the form of tablets or capsules, wherein the release of the active ingredient is controlled by using a reservoir or a matrix system. However, extended release solid compositions suffer from certain drawbacks such as difficulty in swallowing, particularly for certain groups of patients, e.g., pediatrics and geriatrics, resulting in poor patient compliance. Further, high doses of active ingredient lead to large-sized compositions which aggravates this problem.
In view of all this, extended release liquid compositions provide the best alternative over extended release solid compositions. Extended release liquid compositions are easy to administer, thereby leading to enhanced patient compliance. Additionally, extended release liquid compositions provide a unique advantage of having a flexible dosing regimen.
US Patent No. 8,062,667 B2 discloses pharmaceutical preparations comprising active ingredient(s) bound to an ion-exchange resin to provide a active ingredient-ion exchange resin complex, admixing of such complex with a release retardant water-insoluble polymer, and coating of such admixture with a highly flexible, substantially tack-free, non-ionic, water-insoluble, water-permeable diffusion membrane which is preferably aqueous-based and provides a coating membrane that maintains its film integrity, and further provides controllable modified release of the active pharmaceutical(s) in the gastrointestinal tract for a duration of up to about 24 hours.
US Patent No. 8,287,903 B2 discloses methylphenidate extended release powder blend formulation which is reconstitutable into an orally administered aqueous extended release suspension formulation. The extended release powder blend formulation comprises (i) an immediate release methylphenidate component, (ii) a sustained release barrier coated methylphenidate-ion exchange resin complex-matrix, and (iii) an optional water soluble buffering agent.
The inventors of the present invention have developed extended-release suspension composition combination of Dextromethorphan or its pharmaceutically acceptable salts and Chlorpheniramine or its pharmaceutically acceptable salts, Phenylephrine or its pharmaceutically acceptable salts and pharmaceutically acceptable excipients. Further, the inventors of the present invention have also developed a process for the preparation of extended-release suspension composition.

OBJECTIVE OF THE INVENTION
The main objective of the present invention is to provide an extended-release suspension composition.
Another objective of the present invention is to provide an extended-release suspension composition comprising active ingredients and pharmaceutically acceptable excipients, wherein said composition is in the form of powder for suspension or a ready to use suspension.
Another objective of the present invention is to provide an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts as first active ingredient and second active ingredient selected from anti-histamine and decongestant.
Another objective of the present invention is to provide an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts as first active ingredient, second active ingredient and third active ingredient selected from anti-histamine and/or decongestant.
Another objective of the present invention is to provide an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts and Chlorpheniramine or its pharmaceutically acceptable salts and pharmaceutically acceptable excipients.
Another objective of the present invention is to provide an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts and Phenylephrine or its pharmaceutically acceptable salts and pharmaceutically acceptable excipients.
The present invention specifically relates to an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts, Chlorpheniramine or its pharmaceutically acceptable salts, Phenylephrine or its pharmaceutically acceptable salts and pharmaceutically acceptable excipients.
Another objective of the present invention is to provide process for the preparation of an extended-release suspension composition.

SUMMARY OF THE INVENTION
Accordingly, the present invention relates to an extended-release suspension composition.
Another embodiment of the present invention relates to an extended-release suspension composition comprising active ingredients and pharmaceutically acceptable excipients.
Another embodiment of the present invention relates to an extended-release suspension composition comprising active ingredient and pharmaceutically acceptable excipients, wherein said composition is in the form of powder for suspension or a ready to use suspension.
Another embodiment of the present invention relates to an extended-release suspension composition comprising Dextromethorphan or its pharmaceutically acceptable salts and pharmaceutically acceptable excipients.
Another embodiment of the present invention relates to an extended-release suspension composition comprising combination of first active ingredient, second active ingredient and pharmaceutically acceptable excipients.
Another embodiment of the present invention relates to an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts as first active ingredient and second active ingredient selected from anti-histamine and decongestant.
Another embodiment of the present invention relates to an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts as first active ingredient and second active ingredient selected from anti-histamine and decongestant wherein said composition is in the form of powder for suspension or a ready to use suspension.
Another embodiment of the present invention relates to an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts as first active ingredient, second active ingredient and third active ingredient selected from anti-histamine and decongestant.
Another embodiment of the present invention relates to an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts and Chlorpheniramine or its pharmaceutically acceptable salts and pharmaceutically acceptable excipients.
Another embodiment of the present invention relates to an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts and Phenylephrine or its pharmaceutically acceptable salts and pharmaceutically acceptable excipients.
Another embodiment of the present invention relates to an extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts, Chlorpheniramine or its pharmaceutically acceptable salts, Phenylephrine or its pharmaceutically acceptable salts and pharmaceutically acceptable excipients.
Another embodiment of the present invention relates to an extended-release suspension composition comprising excipients selected from Ion exchange resin, solvation coating agent, entrapment polymers, polymers, plasticizers, taste masking agents, sweetening agents, pH adjusting agents/buffering agents, anti-tacking agents, suspending agents/thickeners, preservatives, flavouring agents, surfactants and solvents.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated first active ingredient-ion exchange resin complex comprising:
(i) active ingredient particulate matrix comprising first active ingredient-ion exchange resin complex,
(ii) solvation coating on the first active ingredient-ion exchange resin complex,
(iii) one or more functional barrier coating on the pre-coated first active ingredient-ion exchange resin complex obtained in step (ii), wherein said functional barrier coating provide modified release profile to said first active ingredient, and
b) polymeric coated second active ingredient-ion exchange resin complex comprising:
(i) active ingredient particulate matrix comprising second active ingredient-ion exchange resin complex,
(ii) solvation coating on the second active ingredient-ion exchange resin complex,
(iii) one or more functional barrier coating on the pre-coated second active ingredient-ion exchange resin complex obtained in step (ii), wherein said functional barrier coating provide modified release profile to said second active ingredient, and
c) pharmaceutically acceptable excipients for suspension preparation.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated first active ingredient-ion exchange resin complex comprising:
(i) active ingredient particulate matrix comprising first active ingredient-ion exchange resin complex,
(ii) solvation coating on the first active ingredient-ion exchange resin complex,
(iii) one or more functional barrier coating on the pre-coated first active ingredient-ion exchange resin complex obtained in step (ii), wherein said functional barrier coating provide modified release profile to said first active ingredient, and
b) uncoated first active ingredient-ion exchange resin complex comprising active ingredient particulate matrix comprising first active ingredient-ion exchange resin complex,
c) polymeric coated second active ingredient-ion exchange resin complex comprising:
(i) active ingredient particulate matrix comprising second active ingredient-ion exchange resin complex,
(ii) solvation coating on the second active ingredient-ion exchange resin complex,
(iii) one or more functional barrier coating on the pre-coated second active ingredient-ion exchange resin complex obtained in step (ii), wherein said functional barrier coating provide modified release profile to said second active ingredient, and
d) pharmaceutically acceptable excipients for suspension preparation.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated first active ingredient-ion exchange resin complex comprising:
(i) active ingredient particulate matrix comprising first active ingredient-ion exchange resin complex,
(ii) solvation coating on the first active ingredient-ion exchange resin complex,
(iii) one or more functional barrier coating on the pre-coated first active ingredient-ion exchange resin complex obtained in step (ii), wherein said functional barrier coating provide modified release profile to said first active ingredient,
b) uncoated first active ingredient-ion exchange resin complex comprising active ingredient particulate matrix comprising first active ingredient-ion exchange resin complex,
c) uncoated second active ingredient-ion exchange resin complex comprising active ingredient particulate matrix comprising second active ingredient-ion exchange resin complex, and
d) pharmaceutically acceptable excipients for suspension preparation.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated first active ingredient-ion exchange resin complex comprising:
(i) active ingredient particulate matrix comprising first active ingredient-ion exchange resin complex,
(ii) solvation coating on the first active ingredient-ion exchange resin complex,
(iii) one or more functional barrier coating on the pre-coated first active ingredient-ion exchange resin complex obtained in step (ii), wherein said functional barrier coating provide modified release profile to said first active ingredient,
b) uncoated first active ingredient-ion exchange resin complex comprising active ingredient particulate matrix comprising first active ingredient-ion exchange resin complex,
c) polymeric coated second active ingredient-ion exchange resin complex comprising:
(i) active ingredient particulate matrix comprising second active ingredient-ion exchange resin complex,
(ii) solvation coating on the second active ingredient-ion exchange resin complex,
(iii) one or more functional barrier coating on the pre-coated second active ingredient-ion exchange resin complex obtained in step (ii), wherein said functional barrier coating provide modified release profile to said second active ingredient,
d) uncoated second active ingredient-ion exchange resin complex comprising active ingredient particulate matrix comprising second active ingredient-ion exchange resin complex, and
e) pharmaceutically acceptable excipients for suspension preparation.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated first active ingredient-ion exchange resin complex comprising:
(i) active ingredient particulate matrix comprising first active ingredient-ion exchange resin complex,
(ii) solvation coating on the first active ingredient-ion exchange resin complex,
(iii) one or more functional barrier coating on the pre-coated first active ingredient-ion exchange resin complex obtained in step (ii), wherein said functional barrier coating provide modified release profile to said first active ingredient,
b) polymeric coated second active ingredient-ion exchange resin complex comprising:
(i) active ingredient particulate matrix comprising second active ingredient-ion exchange resin complex,
(ii) solvation coating on the second active ingredient-ion exchange resin complex,
(iii) one or more functional barrier coating on the pre-coated second active ingredient-ion exchange resin complex obtained in step (ii), wherein said functional barrier coating provide modified release profile to said second active ingredient,
c) polymeric coated third active ingredient-ion exchange resin complex comprising:
(i) active ingredient particulate matrix comprising third active ingredient-ion exchange resin complex,
(ii) solvation coating on the third active ingredient-ion exchange resin complex,
(iii) one or more functional barrier coating on the pre-coated third active ingredient-ion exchange resin complex obtained in step (ii), wherein said functional barrier coating provide modified release profile to said third active ingredient, and
d) pharmaceutically acceptable excipients for suspension preparation.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated first active ingredient-ion exchange resin complex comprising:
(i) active ingredient particulate matrix comprising first active ingredient-ion exchange resin complex,
(ii) solvation coating on the first active ingredient-ion exchange resin complex,
(iii) one or more functional barrier coating on the pre-coated first active ingredient-ion exchange resin complex obtained in step (ii), wherein said functional barrier coating provide modified release profile to said first active ingredient,
b) uncoated second active ingredient-ion exchange resin complex comprising active ingredient particulate matrix comprising second active ingredient-ion exchange resin complex,
c) polymeric coated third active ingredient-ion exchange resin complex comprising:
(i) active ingredient particulate matrix comprising third active ingredient-ion exchange resin complex,
(ii) solvation coating on the third active ingredient-ion exchange resin complex,
(iii) one or more functional barrier coating on the pre-coated third active ingredient-ion exchange resin complex obtained in step (ii), wherein said functional barrier coating provide modified release profile to said third active ingredient, and
d) pharmaceutically acceptable excipients for suspension preparation.

Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated first active ingredient-ion exchange resin complex comprising:
(i) active ingredient particulate matrix comprising first active ingredient-ion exchange resin complex,
(ii) solvation coating on the first active ingredient-ion exchange resin complex,
(iii) one or more functional barrier coating on the pre-coated first active ingredient-ion exchange resin complex obtained in step (ii), wherein said functional barrier coating provide modified release profile to said first active ingredient,
b) uncoated first active ingredient-ion exchange resin complex comprising active ingredient particulate matrix comprising first active ingredient-ion exchange resin complex
c) uncoated second active ingredient-ion exchange resin complex comprising active ingredient particulate matrix comprising second active ingredient-ion exchange resin complex,
d) polymeric coated third active ingredient-ion exchange resin complex comprising:
(i) active ingredient particulate matrix comprising third active ingredient-ion exchange resin complex,
(ii) solvation coating on the third active ingredient-ion exchange resin complex,
(iii) one or more functional barrier coating on the pre-coated third active ingredient-ion exchange resin complex obtained in step (ii), wherein said functional barrier coating provide modified release profile to said third active ingredient, and
e) pharmaceutically acceptable excipients for suspension preparation.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide, and
b) polymeric coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) solvation coating on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Chlorpheniramine maleate, and
c) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide, and
b) polymeric coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) solvation coating on the Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Phenylephrine hydrochloride -sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Phenylephrine hydrochloride, and
c) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide,
b) polymeric uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) polymeric coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) solvation coating on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Chlorpheniramine maleate, and
d) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide, and
b) polymeric uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) polymeric coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride -sodium polystyrene sulfonate,
(ii) solvation coating on the Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Phenylephrine hydrochloride, and
d) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide,
b) polymeric uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) polymeric uncoated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
d) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide, and
b) polymeric uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) polymeric uncoated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride -sodium polystyrene sulfonate,
d) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide,
b) polymeric uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) polymeric coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) solvation coating on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Chlorpheniramine maleate, and
d) polymeric uncoated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
e) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide, and
b) polymeric uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) polymeric coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) solvation coating on the Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Phenylephrine hydrochloride, and
d) polymeric uncoated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
e) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide, and
b) polymeric coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) solvation coating on the Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Phenylephrine hydrochloride,
c) polymeric coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) solvation coating on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Chlorpheniramine maleate, and
d) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.
Another embodiment of the present invention relates to an extended-release suspension composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide,
b) polymeric uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) polymeric coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) solvation coating on the Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Phenylephrine hydrochloride,
d) polymeric uncoated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate, and
e) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.
Another embodiment of the present invention relates to a process for the preparation of extended-release suspension composition, wherein said process comprises:
(a) preparing active ingredient-ion exchange resin complex,
(b) coating on active ingredient-ion exchange resin complex with solvation coating polymers,
(c) coating on pre-coated active ingredient-ion exchange resin complex with functional barrier coating polymers, and
(d) mixing of functional coated active ingredient-ion exchange resin complex with excipients.
Another embodiment of the present invention relates to a process for the preparation of extended-release suspension composition, wherein said process comprises:
(a) preparing first active ingredient-ion exchange resin complex,
(b) coating on first active ingredient-ion exchange resin complex with solvation coating polymers,
(c) coating on pre-coated first active ingredient-ion exchange resin complex with functional barrier coating polymers,
(d) preparing second active ingredient-ion exchange resin complex,
(e) coating on second active ingredient-ion exchange resin complex with solvation coating polymers,
(f) coating on pre-coated second active ingredient-ion exchange resin complex with functional barrier coating polymers,
(g) preparing suspension by mixing coated first active ingredient-ion exchange resin complex obtained in step (c), coated first active ingredient-ion exchange resin complex obtained in step (f) and other excipients.
Another embodiment of the present invention relates to a process for the preparation of extended-release suspension composition, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) preparing Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii), and
c) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Chlorpheniramine maleate coated granules.
Another embodiment of the present invention relates to a process for the preparation of extended-release suspension composition, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) preparing Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the on the Phenylephrine hydrochloride-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii), and
c) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Phenylephrine hydrochloride coated granules.
Another embodiment of the present invention relates to a process for the preparation of extended-release suspension composition, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) preparing Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) preparing Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii), and
d) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Chlorpheniramine maleate coated granules.
Another embodiment of the present invention relates to a process for the preparation of extended-release suspension composition, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) preparing Phenylephrine Hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) preparing Phenylephrine hydrochloride particulate matrix comprising Phenylephrine Hydrochloride-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the on the Phenylephrine Hydrochloride-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii), and
d) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Phenylephrine hydrochloride coated granules.
Another embodiment of the present invention relates to a process for the preparation of extended-release suspension composition, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) preparing coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) preparing Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii),
d) preparing coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex, and
e) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Chlorpheniramine maleate coated granules.
Another embodiment of the present invention relates to a process for the preparation of extended-release suspension composition, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) preparing Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) preparing Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the on the Phenylephrine Hydrochloride-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii), and
d) preparing coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex, and
e) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Phenylephrine hydrochloride coated granules.
Another embodiment of the present invention relates to a process for the preparation of extended-release suspension composition, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) preparing Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the on the Phenylephrine Hydrochloride-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Phenylephrine hydrochloride -sodium polystyrene sulfonate complex obtained in step (ii), and
c) preparing coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) preparing Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii),
d) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Phenylephrine hydrochloride coated granules.
Another embodiment of the present invention relates to a process for the preparation of extended-release suspension composition, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) preparing Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) preparing Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the on the Phenylephrine Hydrochloride-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii),
d) preparing coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex, and
e) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Phenylephrine hydrochloride coated granules.

DETAILED DESCRIPTION OF THE INVENTION
The term "comprising", which is synonymous with "including", "containing", or "characterized by" here is defined as being inclusive or open-ended, and does not exclude additional, unrecited elements or method steps, unless the context clearly requires otherwise.
The first active ingredient of the present invention is Dextromethorphan Hydrobromide and second active ingredient is selected from Chlorpheniramine Maleate and Phenylephrine Hydrochloride.
The concentration of active pharmaceutical ingredients used in the extended release suspension composition is from 0.05% to 50% (w/w) of total weight of the composition.
Active ingredient-ion exchange resin complex is formed in such a manner that active ingredient is bound to a pharmaceutically acceptable water insoluble ion exchange resin to form said active ingredient-ion exchange resin complex.
The ion exchange resin as used herein is being selected from
(A) a sulfonated copolymer comprising styrene and divinylbenzene, and
(B) a copolymer comprising styrene and divinylbenzene having quaternary ammonium functional groups.
Ion exchange resin used in the present invention is sodium polystyrene sulfonate.
The concentration of ion exchange resin in the extended release suspension composition is from 2% to 50% (w/w) of total weight of the composition.
Active ingredient-ion exchange resin complex wherein the active ingredient and resin ratio is from 10:1 to 1:10.
Solvation coating over active ingredient-ion exchange resin complex is to enable the effective application thereto of diffusion barrier coatings, resulting in the ability to effectively prolong the release of active ingredients from active ingredient-ion exchange resin complexes. The solvation coating agent as used in the present invention is selected from the group consisting of polyethylene glycol, hypromellose, hydroxy propyl cellulose, povidone and methylcellulose. Preferably, the solvation coating agent is hypromellose, Polyethylene glycol, and povidone.
The concentration of solvation coating agent in the extended release suspension composition is from 0.01% to 10% (w/w) of total weight of the composition.
The entrapment polymers as used in the present invention are selected from the group consisting of a cellulose-derived material such as ethyl cellulose, methyl cellulose, carboxymethyl cellulose, hydroxypropylmethyl cellulose, Methacrylic acid polymers & its co-polymers, sodium alginates, sodium carboxymethyl cellulose. Preferably, entrapment polymer is ethyl cellulose.
The concentration of entrapment polymers in the extended release suspension composition is from 0.01% to 10% (w/w) of total weight of the composition.
The polymers used for the one or more functional barrier coatings on the active ingredient-ion exchange resin complex as used herein may be water soluble polymers, water insoluble polymers, water permeable polymers.
Water soluble polymers used alone or in combination in the compositions of the present invention include, but are not limited to gum arabic or a partially or totally synthetic polymer selected from the alkyl celluloses and derivatives thereof such as methylcellulose, hydroxyalkyl celluloses and derivatives thereof such as hydroxyethyl celluloses, hydroxypropyl celluloses, hydroxyalkyl alkylcelluloses and derivatives thereof such as the hydroxypropylmethyl celluloses (hypromelloses), carboxyalkylcelluloses such as carboxymethylcelluloses, polyvinylpyrrolidones, copolymers of N-vinylpyrrolidone and vinyl acetate or combinations of said polymers and derivatives and mixtures thereof. Preferably used functional barrier coating polymers are ethyl cellulose and hypromellose.
Water insoluble polymers used alone or in combination in the compositions of the present invention include, but are not limited to celluloses, ethyl cellulose, acrylic resin, polymers or coplymers of acrylic acid, methyl acrylate, ethyl acrylate, methacrylic acid, methyl methacrylate, ethyl methacrylate and the like which may contain quaternary ammonium groups such as ammonio (meth)acrylate copolymers. Preferred examples are copolymers of ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate chloride. Such an acrylic polymer is available under the name Eudragit RS which is a water-insoluble copolymer (poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride) 1:2:0.1, manufactured by Rh6m Pharma, Germany) e.g. in form of organic-based polymeric solutions or aqueous-based polymeric dispersions thereof which may be used for coating, for example Eudragit RS 30D. Another acrylic polymer may be Eudragit RL which consists of the same components as Eudragit RS but has a different molar ratio (Eudragit RL: poly(ethylacrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride; 1:2:0.2) e.g. in form of organic-based polymeric solutions or aqueous-based polymeric dispersions thereof, for example Eudragit RL 30D, .
Water permeable polymers used alone or in combination in the compositions of the present invention include, but are not limited to non-acrylic polyolefins, such as low density polyethylene, high density polyethylene, polypropylene, polystyrene, polyvinylchloride, acrylonitrilebutadiene-styrene terpolymers, styrene-acrylonitrile copolymer, styrene butadiene copolymers, poly (4-methyl-pentene-1), polybutylene, polyvinylidene chloride, polyvinyl butyral, chlorinated polyethylene, ethylene-vinyl acetate copolymers, polyvinyl acetate, polyvinyl alcohol, and combinations and blends thereof; acrylic polyoflefins, such as polymethyl-methacrylate, polymethyl-acrylate, ethyleneacrylic acid copolymers, ethylene-acrylic acid metal salt copolymers, and combinations and blends thereof; oxidation polymers, including polyphenylene oxide; and condensation polymers including polyethylene terephthalate, polybutylene terephthalate, Nylon 6, Nylon 11, Nylon 13, Nylon-6,6, polycarbonates, polysulfone, and combinations and blends thereof.
The concentration of barrier coating polymers in the extended release suspension composition is from 0.01% to 10% (w/w) of total weight of the composition.
The compositions of the present invention may further include plasticizer, taste masking agents, sweetening agent, buffering agents, anti-tacking agents, suspending agents/thickeners, preservatives, flavouring agents, surfactants, and lubricants.
Plasticizer is used alone or in combination in the compositions of the present invention include, but are not limited to dibutyl sebacate, propylene glycol, polyethylene glycol, polyvinyl alcohol, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, tributyl citrate, triacetin, and Soluphor® P (2- pyrrolidone), and mixtures thereof. Preferably, the plasticizer is dibutyl sebacate.
The concentration of plasticizer in the extended release suspension composition is from 0.01% to 10% (w/w) of total weight of the composition.
Taste masking agents used alone or in combination in the compositions of the present invention include, but are not limited to osmolality adjusting ingredient, flavouring agent and film-forming agents. Osmolality adjusting ingredient is selected from potassium chloride, calcium chloride, sodium lactate, sodium chloride, dextrose, mannitol, sucrose, trehalose, and phosphate buffered saline, or mixtures thereof. Flavouring agent is selected from vanillin, ethyl vanillin, menthol, citric acid, fumaric acid ethyl maltitol, and tartaric acid. Film-forming agent is selected from pullulan, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, sodium alginate, polyethylene glycol, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl polymer, amylose, high amylose starch, hydroxypropylated high amylose starch, dextrin, pectin, chitin, chitosan, levan, elsinan, collagen, gelatin, zein, gluten, soy protein isolate, whey protein isolate, casein and mixtures thereof.
The concentration of taste masking agents used in the present compositions is in the range of 0.01% to 20% (w/w) of total weight of the composition.
Sweetening agents used alone or in combination in the compositions of the present invention include, but are not limited to saccharin, saccharin sodium, aspartame, maltitol, zinc gluconate, ethyl maltitol, glycine, acesulfame-K, honey, golden syrup, misri, spray dried licorice root, glycerrhizin, dextrose, sodium gluconate, stevia powder; glucono delta-lactone, ethyl vanillin, vanillin, sucrose, glucose (corn syrup), dextrose, invert sugar, fructose, high fructose corn syrup, sucralose, stevia, dihydrochalcone, maltodextrin, polydextrose, sugar alcohols such as sorbitol, sorbitol syrup, mannitol, xylitol, hexa-resorcinol. Preferably used sweetening agent is sucrose, sucralose, xylitol, high fructose corn syrup and combinations thereof.
The concentration of sweetening agent used in the present compositions is in the range of 0.1% to 90% (w/w) of total weight of the composition.
pH adjusting agents/buffering agent used alone or in combination in the compositions of the present invention include, but are not limited to phosphoric acid, monobasic sodium or potassium phosphate, triethanolamine (TRIS), BICINE, HEPES, Trizma, glycine, histidine, arginine, lysine, asparagine, aspartic acid, glutamine, glutamic acid, carbonate, bicarbonate, potassium metaphosphate, potassium phosphate, monobasic sodium acetate, acetic acid, acetate, citric acid, sodium citrate anhydrous, sodium citrate dihydrate and combinations thereof. In certain embodiments, an acid or a base is added to adjust the pH. Suitable acids or bases include HCl, NaOH and KOH. Preferably used pH adjusting agent is citric acid, sodium citrate anhydrous, sodium citrate dihydrate.
The concentration of pH adjusting agents used in the present compositions is in the range of 0.01% to 10% (w/w) of total weight of the composition.
Anti-tacking agents used alone or in combination in the compositions of the present invention include, but are not limited to silicon dioxide, titanium dioxide, alumina, talc, kaolin, powdered cellulose and microcrystalline cellulose. Preferably, anti-tacking agents used in the composition are silicon dioxide, talc.
The concentration of anti-tacking agents used in the present compositions is in the range of 0.01% to 5% (w/w) of total weight of the composition.
Suspending agents/thickeners, used alone or in combination in the compositions of the present invention include, but are not limited to xanthan gum, microcrystalline cellulose, starch, acacia, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, tragacanth and combinations thereof. Preferably, Suspending agents/thickeners used are xanthan gum, microcrystalline cellulose, starch, carboxymethyl cellulose, sodium carboxymethyl cellulose and combinations thereof.
The concentration of Suspending agents/thickeners used in the present compositions is in the range of 0.01% to 20% (w/w) of total weight of the composition.
Preservatives used alone or in combination in the compositions of the present invention include, but are not limited to methylparaben, propylparaben, sodium methylparaben, sodium propylparaben, Sodium metabisulphite, potassium sorbate, sodium benzoate, benzoic acid, disodium EDTA, citric acid, tartaric acid, fumaric acid, malic acid and mixtures thereof. Preferably, preservatives are methylparaben, propylparaben, sodium methylparaben, sodium propylparaben, Sodium metabisulphite and combinations thereof.
The concentration of preservatives used in the present compositions is in the range of 0.01% to 10% (w/w) of total weight of the composition.
Flavouring agents used alone or in combination in the compositions of the present invention include, but are not limited to coffee extract, mint, lamiacea extracts, lemon flavour, almond oil, babassu oil, banana flavour, flavour orange, cherry flavour, caramel flavour, bubblegum flavour, borage oil, blackcurrant seed oil, canola oil, castor oil, coconut oil, corn oil, cottonseed oil, evening primrose oil, grape seed oil, strawberry flavor, groundnut oil, mustard seed oil, olive oil, palm oil, palm kernel oil, peanut oil, grape seed oil, safflower oil, sesame oil, shark liver oil, soybean oil, sunflower oil; hydrogenated castor oil, hydrogenated coconut oil, hydrogenated palm oil, hydrogenated soybean oil, hydrogenated vegetable oil, hydrogenated cottonseed and castor oil, partially hydrogenated soybean oil, soy oil, glyceryl tricaproate, glyceryl tricaprylate, glyceryl tricaprate, glyceryl triundecanoate, glyceryl trilaurate, glyceryl trioleate, glyceryl trilinoleate, glyceryl trilinolenate, glyceryl tricaprylate/caprate, glyceryl tricaprylate/caprate/laurate, glyceryl tricaprylate/caprate/linoleate, glyceryl tricaprylate/caprate/stearate, saturated polyglycolized glycerides, linoleic glycerides, caprylic/capric glycerides, modified triglycerides, fractionated triglycerides, safrole, citric acid, d-limonene, malic acid and phosphoric acid or salts and/or mixtures thereof. Preferably used flavouring agent is strawberry flavour, banana flavour, flavour orange, grape flavour, caramel flavour, cherry flavour, bubblegum flavour.
The concentration of flavouring agent used in the compositions is in the range of 0.1% to 20% (w/w) of total weight of the composition.
Surfactants used alone or in combination in the compositions of the present invention include, but are not limited to SLS, poloxamers (e.g., poloxamer 188), glycerol Anhydrous, glycerin, polysorbate (e.g., 20 or 80), stearyl hetanoate, caprylic/capric fatty acid esters of saturated fatty alcohols of chain length C12-C-18, isostearyl diglycerol isostearic acid, sodium dodecyl sulphate, isopropyl myristate, isopropyl palmitate, and isopropyl myristate/isopropyl stearate/isopropyl palmitate mixture.
The concentration of surfactant used in the compositions is in the range of 0.01% to 20% (w/w) of total weight of the composition.
Suitable solvents used in compositions of the present invention selected from the group comprising water, ethanol, methylene chloride, isopropyl alcohol, acetone, methanol, or combinations thereof.
Another embodiment of the present invention relates to an extended-release suspension composition comprising functional coated active ingredient-ion exchange resin complex, placebo granules, and pharmaceutically acceptable excipients.
Another embodiment of the present invention relates to a process for the preparation of extended-release suspension composition, wherein said process comprises packing the functional coated active ingredient-ion exchange resin complex particles with pharmaceutically acceptable excipients and optionally with placebo granules in a suitable container.
Another embodiment of the present invention relates to extended-release suspension composition, wherein said composition is devoid of uncoated active ingredient-ion exchange resin complex portion.
The present invention is further illustrated by the following examples which are provided merely to be exemplary of the inventions and is not intended to limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
Example 1:

Sr.No. Ingredients mg/ unit
Active ingredient-ion exchange resin complexation
1 Dextromethorphan Hydrobromide 30.00
2 Sodium polystyrene sulfonate 75.00
3 Purified water Q.S
Total weight of active ingredient- resin complex 105.0
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 21
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG pre-coated granules 126
Functional coating on pre-coated active ingredient-resin complex (sustained release 1 coating) 40% w/w build up on 80 parts of pre-coated active ingredient-ion exchange resin complex
7 Ethylcellulose 29.03
8 Hypromellose 3.23
9 Dibutyl sebacate 4.03
10 Talc 4.03
11 Isopropyl alcohol Q.S
12 Purified water Q.S.
Total weight functional coated granules (a) 141.12
Functional coating on pre-coated active ingredient-resin complex (sustained release 2 coating) – 5% w/w build up on 20 parts of pre-coated active ingredient-ion exchange resin complex
13 Ethylcellulose 0.91
14 Hypromellose 0.10
15 Dibutyl sebacate 0.13
16 Talc 0.13
17 Isopropyl alcohol Q.S
18 Purified water Q.S
Total weight of functional coated granules (b) 26.47
Formula for oral suspension
1 Functional coated granules (sustained release coated particulates a – 40% w/w) 141.12
2 Functional coated granules (sustained release coated particulates b – 5% w/w) 26.47
3 Sucrose 1750
4 Methylparaben 5
5 Propylparaben 0.5
6 Sodium metabisulphite 1.25
7 Glycerol anhydrous 200
8 Xanthan gum 10
9 High fructose corn syrup 650
10 Microcrystalline cellulose and carboxymethyl cellulose 62.5
11 FD&C no. 6 0.125
12 Flavour orange 8.5
13 Polysorbate 80 10
14 Anhydrous citric acid 1.5
15 Purified water Q.S.
Total oral ER suspension q.s to 5 ml

Manufacturing process

step 1: (active ingredient-ion exchange resin complex preparation)
The resin is activated by soaking in water for 1-2 hours. Dextromethorphan hydrobromide was dispersed in water and heated to 75°C to solubilize the active ingredient. The active ingredient-ion exchange resin complex was prepared by adding sodium polystyrene sulfonate to Dextromethorphan hydrobromide solution kept under stirring and under heating for 3 – 5 hours. After complexation, the active ingredient-ion exchange resin dispersion was kept still for active ingredient-ion exchange resin complex to settle down and the solvent was drained. The wet drug-ion exchange resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (Pre-coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol (PEG) in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-ion exchange resin complex.

step 3a: Functional coating on pre-coated active ingredient-resin complex (sustained release 1 coating) – 40% w/w build up on 80 parts of pre-coated active ingredient-ion exchange resin complex
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

step 3b: Functional coating on pre-coated active ingredient-resin complex (sustained release 2 coating) – 5% w/w build up on 20 parts of pre-coated active ingredient-ion exchange resin complex
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

step 4: (preparation of suspension)
Functional coated granules a and b (40% w/w) and Functional coated granules (5% w/w) were mixed with suspension base prepared using sucrose, methyl paraben, propyl paraben, sodium metabisulphite, glycerol anhydrous, xanthan gum, high fructose corn syrup, MCC and CMC (Avicel RC 591), FD&C No. 6, flavour orange, polysorbate 80, anhydrous citric acid. The suspension was packed in suitable container.
Example 2
Sr.No. Ingredients mg/ unit
Dextromethorphan Hydrobromide Coated Granules (30 mg/5 mL)
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 30
2 Sodium polystyrene sulfonate 75
3 Purified water Q.S.
Total resin complex 105
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 21
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 126
Functional coating (approx. 20 % w/w buildup)
7 Ethyl cellulose 10 cps 18.7
8 Hydroxy propyl methyl cellulose 2.1
9 Dibutyl sebacate 2.6
10 Talc 2.6
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 152
Chlorpheniramine Maleate Coated Granules (4 mg/5 mL)
Ion – Resin Complexation
1 Chlorpheniramine Maleate 4
2 Sodium polystyrene sulfonate 10
3 Purified water Q.S.
Total resin complex 14
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 3
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 17
Functional coating (approx. 20 % w/w buildup)
7 Ethyl cellulose 10 cps 2.45
8 Hydroxy propyl methyl cellulose 0.27
9 Dibutyl sebacate 0.34
10 Talc 0.34
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 20.4
Formula for Final Suspension Eq 30 mg/ 5 ml strength
Suspension
1 Dextromethorphan Hydrobromide Coated Granules 152
2 Chlorpheniramine Maleate Coated Granules 20.4
3 microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591) 60
4 Sucrose 1700
5 Glycerin 200
6 Methylparaben 5
7 Propylparaben 0.5
8 Citric acid 1.5
9 High fructose corn syrup 655
10 Xanthan gum 6
11 Flavor Orange 8.5
12 Purified water Q.S. to 5 ml

Manufacturing process
A. Preparation of Dextromethorphan Hydrobromide Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

B. Preparation of Chlorpheniramine Maleate Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Chlorpheniramine Maleate, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

C. Preparation of Final Suspension

step 1: (preparation of suspension)
Sucrose, methylparaben and propylparaben were added to water and heated till 80º C. Rest of the ingredients for suspension along with coated dextromethorphan hydrobromide and chlorpheniramine maleate granules were added. The suspension was packed in suitable container.

Example 3
Sr.No. Ingredients mg/ unit
Dextromethorphan Hydrobromide 20% Coated Granules (a) (30 mg/5 mL)
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 21
2 Sodium polystyrene sulfonate 52.5
3 Purified water Q.S.
Total resin complex 73.5
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 14.7
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 88.2
Functional coating (approx. 20 % w/w buildup)
7 Ethyl cellulose 10 cps 12.7
8 Hydroxy propyl methyl cellulose 1.411
9 Dibutyl sebacate 1.764
10 Talc 1.764
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 105.84
Dextromethorphan 5 % coated granules (b) (30mg/5ml )
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 9
2 Sodium polystyrene sulfonate 22.5
3 Purified water Q.S.
Total resin complex 31.5
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 6.3
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 37.8
Functional coating (approx. 20 % w/w buildup)
7 Ethyl cellulose 10 cps 1.361
8 Hydroxy propyl methyl cellulose 0.151
9 Dibutyl sebacate 0.441
10 Talc 0.441
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 40.19
Chlorpheniramine Maleate Coated Granules (4 mg/5 mL)
Ion – Resin Complexation
1 Chlorpheniramine Maleate 4
2 Sodium polystyrene sulfonate 10
3 Purified water Q.S.
Total resin complex 14
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 3
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 17
Functional coating (approx. 20 % w/w buildup)
7 Ethyl cellulose 10 cps 2.45
8 Hydroxy propyl methyl cellulose 0.27
9 Dibutyl sebacate 0.34
10 Talc 0.34
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 20.4
Formula for Final Suspension Eq 30 mg/ 5 ml strength
Suspension
1 Dextromethorphan Hydrobromide 20 % coated granules (a) 105.84
2 Dextromethorphan Hydrobromide 5 % coated granules (b) 40.19
3 Chlorpheniramine Maleate Coated Granules 20.4
4 microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591) 60
5 Sucrose 1700
6 Glycerin 200
7 Methylparaben 5
8 Propylparaben 0.5
9 Citric acid 1.5
10 High fructose corn syrup 655
11 Xanthan gum 6
12 Flavor Orange 8.5
13 Purified water Q.S. to 5 ml

Manufacturing process

A. Preparation of Dextromethorphan Hydrobromide Coated Granules (both 20% coated (a) and 5% coated (b))

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient -resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)

The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

B. Preparation of Chlorpheniramine Maleate Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Chlorpheniramine Maleate, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

C. Preparation of Final Suspension

step 1: (preparation of suspension)
Sucrose, methylparaben and propylparaben were added to water and heated till 80º C. Rest of the ingredients for suspension along with coated dextromethorphan hydrobromide and chlorpheniramine maleate granules were added. The suspension was packed in suitable container.

Example 4
Sr.No. Ingredients mg/ unit
Dextromethorphan Hydrobromide 20% Coated Granules (30 mg/5 mL)
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 21
2 Sodium polystyrene sulfonate 52.5
3 Purified water Q.S.
Total resin complex 73.5
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 14.7
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 88.2
Functional coating (approx. 20 % w/w buildup)
7 Ethyl cellulose 10 cps 12.7
8 Hydroxy propyl methyl cellulose 1.411
9 Dibutyl sebacate 1.764
10 Talc 1.764
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 105.84
Dextromethorphan Hydrobromide Granules - Uncoated (30mg/5ml )
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 9
2 Sodium polystyrene sulfonate 22.5
3 Purified water Q.S.
Total resin complex 31.5
Chlorpheniramine Maleate Granules - uncoated (4 mg/5 mL)
Ion – Resin Complexation
1 Chlorpheniramine Maleate 4
2 Sodium polystyrene sulfonate 14
3 Purified water Q.S.
Total resin complex 18
PEG coating (approx. 20 % w/w buildup)
Suspension
1 Dextromethorphan Hydrobromide 20 % coated granules 105.84
2 Dextromethorphan Hydrobromide granules - Uncoated 31.50
3 Chlorpheniramine Maleate granules – Uncoated 18.00
4 microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591) 60.00
5 Sucrose 1700.0
6 Glycerin 200.00
7 Methylparaben 5.00
8 Propylparaben 0.50
9 Citric acid 1.50
10 High fructose corn syrup 655.00
11 Xanthan gum 6.00
12 Flavor Orange 8.50
13 Purified water Q.S. to 5 ml

Manufacturing process

A. Preparation of Dextromethorphan Hydrobromide 20% Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)

The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

B. Preparation of Dextromethorphan Hydrobromide uncoated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

C. Preparation of Chlorpheniramine Maleate Granules uncoated

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Chlorpheniramine Maleate, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

D. Preparation of Final Suspension

step 1: (preparation of suspension)
Sucrose, methylparaben and propylparaben were added to water and heated till 80º C. Rest of the ingredients for suspension along with coated dextromethorphan hydrobromide and chlorpheniramine maleate granules were added. The suspension was packed in suitable container.

Example 5
Sr.No. Ingredients mg/ unit
Dextromethorphan Hydrobromide 10% Coated Granules (30 mg/5 mL)
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 21
2 Sodium polystyrene sulfonate 52.5
3 Purified water Q.S.
Total resin complex 73.5
PEG coating
4 PEG 4000 14.7
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 88.2
Functional coating
7 Ethyl cellulose 10 cps 6.35
8 Hydroxy propyl methyl cellulose 0.705
9 Dibutyl sebacate 0.882
10 Talc 0.882
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 98.02
Dextromethorphan Hydrobromide Granules - Uncoated (30mg/5ml )
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 9
2 Sodium polystyrene sulfonate 22.5
3 Purified water Q.S.
Total resin complex 31.5
Chlorpheniramine Maleate Granules - uncoated (4 mg/5 mL)
Ion – Resin Complexation
1 Chlorpheniramine Maleate 4
2 Sodium polystyrene sulfonate 14
3 Purified water Q.S.
Total resin complex 18
PEG coating
Suspension
1 Dextromethorphan Hydrobromide coated granules 98.02
2 Dextromethorphan Hydrobromide granules - Uncoated 31.50
3 Chlorpheniramine Maleate granules – Uncoated 18.00
4 microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591) 60.00
5 Sucrose 1700.0
6 Glycerin 200.00
7 Methylparaben 5.00
8 Propylparaben 0.50
9 Citric acid 1.50
10 High fructose corn syrup 655.00
11 Xanthan gum 6.00
12 Flavor Orange 8.50
13 Purified water Q.S. to 5 ml

Manufacturing process

A. Preparation of Dextromethorphan Hydrobromide 10% Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

B. Preparation of Dextromethorphan Hydrobromide uncoated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

C. Preparation of Chlorpheniramine Maleate Granules uncoated

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Chlorpheniramine Maleate, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

D. Preparation of Final Suspension

step 1: (preparation of suspension)
Sucrose, methylparaben and propylparaben were added to water and heated till 80º C. Rest of the ingredients for suspension along with coated dextromethorphan hydrobromide and chlorpheniramine maleate granules were added. The suspension was packed in suitable container.

Example 6
Sr. No. Ingredients mg/ unit
Dextromethorphan Hydrobromide Coated Granules (30 mg/5 mL)
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 30
2 Sodium polystyrene sulfonate 75
3 Purified water Q.S.
Total resin complex 105
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 21
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 126
Functional coating (approx. 20 % w/w buildup)
7 Ethyl cellulose 10 cps 18.7
8 Hydroxy propyl methyl cellulose 2.1
9 Dibutyl sebacate 2.6
10 Talc 2.6
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 152
Phenylephrine Hydrochloride Coated Granules (10 mg/5 mL)
Ion – Resin Complexation
1 Phenylephrine Hydrochloride 10
2 Sodium polystyrene sulfonate 25
3 Purified water Q.S.
Total resin complex 35
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 7.00
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 42.00
Functional coating (approx. 20 % w/w buildup)
7 Ethyl cellulose 10 cps 6.048
8 Hydroxy propyl methyl cellulose 0.672
9 Dibutyl sebacate 0.84
10 Talc 0.84
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 50.4
Formula for Final Suspension Eq 30 mg/ 5 ml strength
Suspension
1 Dextromethorphan Hydrobromide Coated Granules 152
2 Phenylephrine Hydrochloride Coated Granules 50.4
3 microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591) 60
4 Sucrose 1700
5 Glycerin 200
6 Methylparaben 5
7 Propylparaben 0.5
8 Citric acid 1.5
9 High fructose corn syrup 655
10 Xanthan gum 6
11 Flavor Orange 8.5
12 Purified water Q.S. to 5 ml

Manufacturing process

A. Preparation of Dextromethorphan Hydrobromide Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)

The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

B. Preparation of Phenylephrine Hydrochloride Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Phenylephrine hydrochloride, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

C. Preparation of Final Suspension

step 1: (preparation of suspension)
Sucrose, methylparaben and propylparaben were added to water and heated till 80º C. Rest of the ingredients for suspension along with coated dextromethorphan hydrobromide and Phenylephrine Hydrochloride granules were added. The suspension was packed in suitable container.

Example 7
Sr.No. Ingredients mg/ unit
Dextromethorphan Hydrobromide 20% Coated Granules (a) (30 mg/5 mL)
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 21
2 Sodium polystyrene sulfonate 52.5
3 Purified water Q.S.
Total resin complex 73.5
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 14.7
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 88.2
Functional coating (approx. 20 % w/w buildup)
7 Ethyl cellulose 10 cps 12.7
8 Hydroxy propyl methyl cellulose 1.411
9 Dibutyl sebacate 1.764
10 Talc 1.764
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 105.84
Dextromethorphan 5 % coated granules (b) (30mg/5ml )
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 9
2 Sodium polystyrene sulfonate 22.5
3 Purified water Q.S.
Total resin complex 31.5
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 6.3
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 37.8
Functional coating (approx. 5% w/w buildup)
7 Ethyl cellulose 10 cps 1.361
8 Hydroxy propyl methyl cellulose 0.151
9 Dibutyl sebacate 0.441
10 Talc 0.441
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 40.19
Phenylephrine Hydrochloride Coated Granules (10mg/5 mL)
Ion – Resin Complexation
1 Phenylephrine Hydrochloride 10
2 Sodium polystyrene sulfonate 25
3 Purified water Q.S.
Total resin complex 35
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 7
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 42.00
Functional coating (approx. 20 % w/w buildup)
7 Ethyl cellulose 10 cps 6.048
8 Hydroxy propyl methyl cellulose 0.672
9 Dibutyl sebacate 0.84
10 Talc 0.84
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 50.4
Formula for Final Suspension Eq 30 mg/ 5 ml strength
Suspension
1 Dextromethorphan Hydrobromide 20 % coated granules (a) 105.84
2 Dextromethorphan Hydrobromide 5 % coated granules (b) 40.19
3 Phenylephrine HCl Coated Granules 50.40
4 microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591) 60.00
5 Sucrose 1700.0
6 Glycerin 200.00
7 Methylparaben 5.00
8 Propylparaben 0.50
9 Citric acid 1.50
10 High fructose corn syrup 655.00
11 Xanthan gum 6.00
12 Flavor Orange 8.50
13 Purified water Q.S. to 5 ml

Manufacturing process

A. Preparation of Dextromethorphan Hydrobromide Coated Granules (both 20% Coated (a) and 5% coated (b))

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin )
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

B. Preparation of Phenylephrine Hydrochloride Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Phenylephrine Hydrochloride, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

C. Preparation of Final Suspension

step 1: (preparation of suspension)
Sucrose, methylparaben and propylparaben were added to water and heated till 80º C. Rest of the ingredients for suspension along with coated Dextromethorphan hydrobromide and Phenylephrine Hydrochloride granules were added. The suspension was packed in suitable container.

Example 8
Sr.No. Ingredients mg/ unit
Dextromethorphan Hydrobromide 20% Coated Granules (30 mg/5 mL)
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 21
2 Sodium polystyrene sulfonate 52.5
3 Purified water Q.S.
Total resin complex 73.5
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 14.7
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 88.2
Functional coating (approx. 20 % w/w buildup)
7 Ethyl cellulose 10 cps 12.7
8 Hydroxy propyl methyl cellulose 1.411
9 Dibutyl sebacate 1.764
10 Talc 1.764
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 105.84
Dextromethorphan Hydrobromide Granules - Uncoated (30mg/5ml )
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 9
2 Sodium polystyrene sulfonate 22.5
3 Purified water Q.S.
Total resin complex weight 31.5
Phenylephrine Hydrochloride Coated Granules 10 mg/5 mL)
Ion – Resin Complexation
1 Phenylephrine Hydrochloride 10
2 Sodium polystyrene sulfonate 25
3 Purified water Q.S.
Total resin complex 35
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 7.00
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 42
Functional coating
7 Ethyl cellulose 10 cps 6.048
8 Hydroxy propyl methyl cellulose 0.672
9 Dibutyl sebacate 0.84
10 Talc 0.84
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 50.4
Formula for Final Suspension Eq 30 mg/ 5 ml strength
Suspension
1 Dextromethorphan Hydrobromide 20% coated granules 105.84
2 Dextromethorphan Hydrobromide granules - Uncoated 31.50
3 Phenylephrine Hydrochloride Coated Granules 50.40
4 Avicel RC 591 60.00
5 Sucrose 1700.0
6 Glycerin 200.00
7 Methyl paraben 5.00
8 Propyl paraben 0.50
9 Citric acid 1.50
10 High fructose corn syrup 655.00
11 Xanthan gum 6.00
12 Flavor Orange 8.50
13 Purified water Q.S. to 5 ml

Manufacturing process

A. Preparation of Dextromethorphan Hydrobromide 20% Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

B. Preparation of Dextromethorphan Hydrobromide uncoated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

C. Preparation of Phenylephrine Hydrochloride Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Phenylephrine Hydrochloride, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

D. Preparation of Final Suspension

step 1: (preparation of suspension)
Sucrose, methylparaben and propylparaben were added to water and heated till 80º C. Rest of the ingredients for suspension along with coated dextromethorphan hydrobromide and Phenylephrine Hydrochloride granules were added. The suspension was packed in suitable container.

Example 9
Sr.No. Ingredients mg/ unit
Dextromethorphan Hydrobromide Coated Granules (30 mg/5 mL)
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 21
2 Sodium polystyrene sulfonate 52.5
3 Purified water Q.S.
Total resin complex 73.5
PEG coating
4 PEG 4000 14.7
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 88.2
Functional coating
7 Ethyl cellulose 10 cps 12.7
8 Hydroxy propyl methyl cellulose 1.411
9 Dibutyl sebacate 1.764
10 Talc 1.764
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 105.84
Dextromethorphan Hydrobromide Granules - Uncoated (30mg/5ml )
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 9
2 Sodium polystyrene sulfonate 22.5
3 Purified water Q.S.
Total resin complex weight 31.5
Phenylephrine Hydrochloride Coated Granules 10 mg/5 mL)
Ion – Resin Complexation
1 Phenylephrine Hydrochloride 10
2 Sodium polystyrene sulfonate 25
3 Purified water Q.S.
Total resin complex 35
PEG coating
4 PEG 4000 7.00
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 42
Functional coating
7 Ethyl cellulose 10 cps 6.048
8 Hydroxy propyl methyl cellulose 0.672
9 Dibutyl sebacate 0.84
10 Talc 0.84
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 50.4
Formula for Final Suspension Eq 30 mg/ 5 ml strength
Suspension
1 Dextromethorphan Hydrobromide coated granules 105.84
2 Dextromethorphan Hydrobromide granules - Uncoated 31.50
3 Phenylephrine Hydrochloride Coated Granules 50.40
4 Avicel RC 591 60.00
5 Sucrose 1700.0
6 Glycerin 200.00
7 Methyl paraben 5.00
8 Propyl paraben 0.50
9 Citric acid 1.50
10 High fructose corn syrup 655.00
11 Xanthan gum 6.00
12 Flavor Orange 8.50
13 Purified water Q.S. to 5 ml

Manufacturing process

A. Preparation of Dextromethorphan Hydrobromide Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

B. Preparation of Dextromethorphan Hydrobromide uncoated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

C. Preparation of Phenylephrine Hydrochloride Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Phenylephrine Hydrochloride, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

D. Preparation of Final Suspension

step 1: (preparation of suspension)
Sucrose, methylparaben and propylparaben were added to water and heated till 80º C. Rest of the ingredients for suspension along with coated dextromethorphan hydrobromide and Phenylephrine Hydrochloride granules were added. The suspension was packed in suitable container.

Example 10
Sr.No. Ingredients mg/ unit
Dextromethorphan Hydrobromide Coated Granules (30 mg/5 mL)
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 21
2 Sodium polystyrene sulfonate 52.5
3 Purified water Q.S.
Total resin complex 73.5
PEG coating
4 PEG 4000 14.7
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 88.2
Functional coating
7 Ethyl cellulose 10 cps 6.35
8 Hydroxy propyl methyl cellulose 0.705
9 Dibutyl sebacate 0.882
10 Talc 0.882
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 97.02
Dextromethorphan Hydrobromide Granules - Uncoated (30mg/5ml )
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 9
2 Sodium polystyrene sulfonate 22.5
3 Purified water Q.S.
Total resin complex weight 31.5
Phenylephrine Hydrochloride Coated Granules 10 mg/5 mL)
Ion – Resin Complexation
1 Phenylephrine Hydrochloride 10
2 Sodium polystyrene sulfonate 25
3 Purified water Q.S.
Total resin complex 35
PEG coating
4 PEG 4000 7.00
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 42
Functional coating
7 Ethyl cellulose 10 cps 6.048
8 Hydroxy propyl methyl cellulose 0.672
9 Dibutyl sebacate 0.84
10 Talc 0.84
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 50.4
Formula for Final Suspension Eq 30 mg/ 5 ml strength
Suspension
1 Dextromethorphan coated granules 97.02
2 Dextromethorphan Hydrobromide granules - Uncoated 31.50
3 Phenylephrine Hydrochloride Coated Granules 50.40
4 Avicel RC 591 60.00
5 Sucrose 1700.0
6 Glycerin 200.00
7 Methyl paraben 5.00
8 Propyl paraben 0.50
9 Citric acid 1.50
10 High fructose corn syrup 655.00
11 Xanthan gum 6.00
12 Flavor Orange 8.50
13 Purified water Q.S. to 5 ml

Manufacturing process

A. Preparation of Dextromethorphan Hydrobromide Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

B. Preparation of Dextromethorphan Hydrobromide uncoated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

C. Preparation of Phenylephrine Hydrochloride Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Phenylephrine Hydrochloride, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

D. Preparation of Final Suspension

step 1: (preparation of suspension)
Sucrose, methylparaben and propylparaben were added to water and heated till 80º C. Rest of the ingredients for suspension along with coated dextromethorphan hydrobromide and Phenylephrine Hydrochloride granules were added. The suspension was packed in suitable container.

Example 11
Sr.No. Ingredients mg/ unit
Dextromethorphan Hydrobromide 20% Coated Granules (30 mg/5 mL)
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 21
2 Sodium polystyrene sulfonate 52.5
3 Purified water Q.S.
Total resin complex 73.5
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 14.7
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 88.2
Functional coating (approx. 20 % w/w buildup)
7 Ethyl cellulose 10 cps 12.7
8 Hydroxy propyl methyl cellulose 1.411
9 Dibutyl sebacate 1.764
10 Talc 1.764
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 105.84
Dextromethorphan Hydrobromide Granules - Uncoated (30mg/5ml )
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 9
2 Sodium polystyrene sulfonate 22.5
3 Purified water Q.S.
Total resin complex 31.5
Phenylephrine Hydrochloride Granules - uncoated (10 mg/5 mL)
Ion – Resin Complexation
1 Phenylephrine Hydrochloride 10
2 Sodium polystyrene sulfonate 25
3 Purified water Q.S.
Total resin complex 35
Suspension
1 Dextromethorphan Hydrobromide 20 % coated granules 105.84
2 Dextromethorphan Hydrobromide granules - Uncoated 31.50
3 Phenylephrine Hydrochloride granules – Uncoated 35.00
4 Avicel RC 591 60.00
5 Sucrose 1700.0
6 Glycerin 200.00
7 Methyl paraben 5.00
8 Propyl paraben 0.50
9 Citric acid 1.50
10 High fructose corn syrup 655.00
11 Xanthan gum 6.00
12 Flavor Orange 8.50
13 Purified water Q.S. to 5 ml

Manufacturing process

A. Preparation of Dextromethorphan Hydrobromide 20% Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)

The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

B. Preparation of Dextromethorphan Hydrobromide uncoated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

C. Preparation of Phenylephrine Hydrochloride Granules uncoated

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Phenylephrine Hydrochloride, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

D. Preparation of Final Suspension

step 1: (preparation of suspension)
Sucrose, methylparaben and propylparaben were added to water and heated till 80º C. Rest of the ingredients for suspension along with coated dextromethorphan hydrobromide and Phenylephrine Hydrochloride granules were added. The suspension was packed in suitable container.

Example 12
Sr.No. Ingredients mg/ unit
Dextromethorphan Hydrobromide 20% Coated Granules (30 mg/5 mL)
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 21
2 Sodium polystyrene sulfonate 52.5
3 Purified water Q.S.
Total resin complex 73.5
PEG coating (approx. 20 % w/w buildup)
4 PEG 4000 14.7
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 88.2
Functional coating (approx. 20 % w/w buildup)
7 Ethyl cellulose 10 cps 12.7
8 Hydroxy propyl methyl cellulose 1.411
9 Dibutyl sebacate 1.764
10 Talc 1.764
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 105.84
Dextromethorphan Hydrobromide Granules - Uncoated (30mg/5ml )
Ion – Resin Complexation
1 Dextromethorphan Hydrobromide 9
2 Sodium polystyrene sulfonate 22.5
3 Purified water Q.S.
Total resin complex weight 31.5
Phenylephrine Hydrochloride 20% Coated Granules (10 mg/5 mL)
Ion – Resin Complexation
1 Phenylephrine Hydrochloride 10
2 Sodium polystyrene sulfonate 25
3 Purified water Q.S.
Total resin complex 35.00
PEG coating
4 PEG 4000 7.00
5 Isopropyl alcohol Q.S.
6 Purified water Q.S.
Total PEG coated granules 42.00
Functional coating (approx. 20 % w/w buildup)
7 Ethyl cellulose 10 cps 6.048
8 Hydroxy propyl methyl cellulose 0.672
9 Dibutyl sebacate 0.84
10 Talc 0.84
11 Isopropyl alcohol Q.S.
12 Purified water Q.S.
Total functional coated granules 50.4
Chlorpheniramine Maleate Granules - Uncoated
1 Chlorpheniramine Maleate 4
2 Sodium polystyrene sulfonate 10
3 Purified water Q.S.
Total resin complex 14
Formula for Final Suspension Eq 30 mg/ 5 ml strength
Suspension
1 Dextromethorphan Hydrobromide 20 % coated granules 105.84
2 Dextromethorphan Hydrobromide granules - Uncoated 31.50
3 Phenylephrine Hydrochloride 20 % coated granules 50.40
4 Chlorpheniramine Maleate granules – uncoated 14.00
6 Avicel RC 591 60.00
7 Sucrose 1700.0
8 Glycerin 200.00
9 Methylparaben 5.00
10 Propylparaben 0.50
11 Citric acid 1.50
12 High fructose corn syrup 655.00
13 Xanthan gum 6.00
14 Flavor Orange 8.50
15 Purified water Q.S. to 5 ml

Manufacturing process

A. Preparation of Dextromethorphan Hydrobromide 20% Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin)
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

B. Preparation of Dextromethorphan Hydrobromide uncoated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Dextromethorphan Hydrobromide, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

C. Preparation of Phenylephrine Hydrochloride Coated Granules

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Phenylephrine Hydrochloride, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

step 2: (PEG coating of active ingredient-resin complex)
The coating solution was prepared by dispersing polyethylene glycol in isopropyl alcohol and purified water under stirring for 45 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the active ingredient-resin complex.

step 3: (functional coating on PEG-coated active ingredient-resin
The coating solution was prepared by dispersing ethylcellulose, dibutyl sebacate, hypromellose and talc in isopropyl alcohol and purified water under stirring for 60 minutes. The coating process was performed in a fluid bed processor by applying coating solution to the pre-coated active ingredient-resin complex.

D. Preparation of Chlorpheniramine Maleate Granules uncoated

step 1: (active ingredient-resin complex preparation)
The active ingredient-resin complex was prepared by adding Chlorpheniramine Maleate, sodium polystyrene sulfonate and to purified water and stirred for 3 - 4 hours. After complexation, the active ingredient-resin dispersion was kept still for active ingredient-resin complex to settle down and the solvent was drained. The wet drug-resin complex was collected by filtration and dried using fluidized bed dryer.

E. Preparation of Final Suspension

step 1: (preparation of suspension)
Sucrose, methylparaben and propylparaben were added to water and heated till 80º C. Rest of the ingredients for suspension along with coated dextromethorphan hydrobromide and Chlorpheniramine Maleate granules and Phenylephrine Hydrochloride granules were added. The suspension was packed in suitable container. , Claims:
We Claim:
1. An extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts as first active ingredient and second active ingredient selected from anti-histamine and decongestant wherein said composition is in the form of powder for suspension or a ready to use suspension.

2. The composition as claimed in claim 1, wherein said extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts and Chlorpheniramine or its pharmaceutically acceptable salts and pharmaceutically acceptable excipients.

3. The composition as claimed in claim 1, wherein said extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts and Phenylephrine or its pharmaceutically acceptable salts and pharmaceutically acceptable excipients.

4. The composition as claimed in claim 1, wherein said extended-release suspension composition comprising third active ingredient selected from anti-histamine and decongestant.

5. The composition as claimed in claim 1 to 4, wherein said extended-release suspension composition comprising combination of Dextromethorphan or its pharmaceutically acceptable salts, Chorpheniramine or its pharmaceutically acceptable salts, Phenylephrine or its pharmaceutically acceptable salts and pharmaceutically acceptable excipients.

6. The composition as claimed in claim 1, wherein said excipients are selected from Ion exchange resin, solvation coating agent, entrapment polymers, polymers, plasticizers, taste masking agents, sweetening agents, pH adjusting agents/buffering agents, anti-tacking agents, suspending agents/thickeners, preservatives, flavouring agents and solvents.

7. The composition as claimed in claim 6, wherein said Ion exchange resin is sodium polystyrene sulfonate.

8. The composition as claimed in claim 6, wherein said solvation coating agent is selected from the group consisting of polyethylene glycol, hypromellose, hydroxy propyl cellulose, povidone and methylcellulose.

9. The composition as claimed in claim 6, wherein said entrapment polymers are selected from the group consisting of a cellulose-derived material such as ethyl cellulose, methyl cellulose, carboxymethyl cellulose, hydroxypropylmethyl cellulose, Methacrylic acid polymers & its co-polymers, sodium alginates, sodium carboxymethyl cellulose.

10. The composition as claimed in claim 6, wherein said plasticizer are selected from dibutyl sebacate, propylene glycol, polyethylene glycol, polyvinyl alcohol, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, tributyl citrate, triacetin, and 2- pyrrolidone and mixtures thereof.

11. The composition as claimed in claim 6, wherein said taste masking agents is selected from potassium chloride, calcium chloride, sodium lactate, sodium chloride, dextrose, mannitol, sucrose, trehalose, phosphate buffered saline, vanillin, ethyl vanillin, menthol, citric acid, fumaric acid ethyl maltitol, tartaric acid, pullulan, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, sodium alginate, polyethylene glycol, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl polymer, amylose, high amylose starch, hydroxypropylated high amylose starch, dextrin, pectin, chitin, chitosan, levan, elsinan, collagen, gelatin, zein, gluten, soy protein isolate, whey protein isolate, casein and mixtures thereof.

12. The composition as claimed in claim 6, wherein said sweetening agents are selected from saccharin, saccharin sodium, aspartame, maltitol, zinc gluconate, ethyl maltitol, glycine, acesulfame-K, honey, golden syrup, misri, spray dried liquorice root, glycerrhizin, dextrose, sodium gluconate, stevia powder, glucono delta-lactone, ethyl vanillin, vanillin, sucrose, glucose (corn syrup), dextrose, invert sugar, fructose, high fructose corn syrup, sucralose, stevia, dihydrochalcone, maltodextrin, polydextrose, sugar alcohols such as sorbitol, sorbitol syrup, mannitol, xylitol, hexa-resorcinol.

13. The composition as claimed in claim 6, wherein said pH adjusting agents/buffering agent are selected from phosphoric acid, monobasic sodium or potassium phosphate, triethanolamine (TRIS), BICINE, HEPES, Trizma, glycine, histidine, arginine, lysine, asparagine, aspartic acid, glutamine, glutamic acid, carbonate, bicarbonate, potassium metaphosphate, potassium phosphate, monobasic sodium acetate, acetic acid, acetate, citric acid, sodium citrate anhydrous, sodium citrate dihydrate and combinations thereof.

14. The composition as claimed in claim 6, wherein said anti-tacking agents are selected from silicon dioxide, titanium dioxide, alumina, talc, kaolin, powdered cellulose and microcrystalline cellulose.

15. The composition as claimed in claim 6, wherein said suspending agents/thickeners are selected from xanthan gum, microcrystalline cellulose, starch, acacia, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, tragacanth and combinations thereof.

16. The composition as claimed in claim 6, wherein said preservatives are selected from methylparaben, propylparaben, sodium methylparaben, sodium propylparaben, Sodium metabisulphite, potassium sorbate, sodium benzoate, benzoic acid, disodium EDTA, citric acid, tartaric acid, fumaric acid, malic acid and mixtures thereof.

17. The composition as claimed in claim 6, wherein said flavouring agents are selected from coffee extract, mint, lamiacea extracts, lemon flavour, almond oil, babassu oil, banana flavour, flavour orange, cherry flavour, caramel flavour, bubblegum flavour, borage oil, blackcurrant seed oil, canola oil, castor oil, coconut oil, corn oil, cottonseed oil, evening primrose oil, grape seed oil, strawberry flavor, groundnut oil, mustard seed oil, olive oil, palm oil, palm kernel oil, peanut oil, grape seed oil, safflower oil, sesame oil, shark liver oil, soybean oil, sunflower oil; hydrogenated castor oil, hydrogenated coconut oil, hydrogenated palm oil, hydrogenated soybean oil, hydrogenated vegetable oil, hydrogenated cottonseed and castor oil, partially hydrogenated soybean oil, soy oil, glyceryl tricaproate, glyceryl tricaprylate, glyceryl tricaprate, glyceryl triundecanoate, glyceryl trilaurate, glyceryl trioleate, glyceryl trilinoleate, glyceryl trilinolenate, glyceryl tricaprylate/caprate, glyceryl tricaprylate/caprate/laurate, glyceryl tricaprylate/caprate/linoleate, glyceryl tricaprylate/caprate/stearate, saturated polyglycolized glycerides, linoleic glycerides, caprylic/capric glycerides, modified triglycerides, fractionated triglycerides, safrole, citric acid, d-limonene, malic acid and phosphoric acid or salts or mixtures thereof.

18. The composition as claimed in claim 6, wherein said solvents are selected from water, ethanol, methylene chloride, isopropyl alcohol, acetone, methanol or combinations thereof.

19. The composition as claimed in claims 1-18, wherein said composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water,
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide, and
b) polymeric coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) solvation coating on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Chlorpheniramine maleate, and
c) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.

20. The composition as claimed in claims 1-18, wherein said composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide, and
b) polymeric coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) solvation coating on the Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Phenylephrine hydrochloride, and
c) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.

21. The composition as claimed in claims 1-18, wherein said composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide,
b) polymeric uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) polymeric coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) solvation coating on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Chlorpheniramine maleate, and
d) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.

22. The composition as claimed in claims 1-18, wherein said composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide, and
b) polymeric uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) polymeric coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) solvation coating on the Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Phenylephrine hydrochloride, and
d) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.

23. The composition as claimed in claims 1-18, wherein said composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide,
b) polymeric uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) polymeric uncoated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
d) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.

24. The composition as claimed in claims 1-18, wherein said composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide,
b) polymeric uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) polymeric uncoated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
d) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.

25. The composition as claimed in claims 1-18, wherein said composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide,
b) polymeric uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) polymeric coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) solvation coating on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Chlorpheniramine maleate, and
d) polymeric uncoated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
e) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.

26. The composition as claimed in claims 1-18, wherein said composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide, and
b) polymeric uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) polymeric coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) solvation coating on the Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Phenylephrine hydrochloride, and
d) polymeric uncoated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
e) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.

27. The composition as claimed in claims 1-18, wherein said composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide, and
b) polymeric coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) solvation coating on the Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water,
(iii) one or more functional barrier coating on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Phenylephrine hydrochloride,
c) polymeric coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) solvation coating on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Chlorpheniramine maleate, and
d) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.

28. The composition as claimed in claims 1-18, wherein said composition comprising:
a) polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) solvation coating on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water
(iii) one or more functional barrier coating on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Dextromethorphan hydrobromide, and
b) polymeric uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) polymeric coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) solvation coating on the Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising polyethylene glycol, isopropyl alcohol and purified water,
(iii) one or more functional barrier coating on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii) comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water, wherein said functional barrier coating provide modified release profile to said Phenylephrine hydrochloride,
d) polymeric uncoated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate, and
e) pharmaceutically acceptable excipients for suspension preparation comprising microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water.

29. The process for the preparation of extended-release suspension composition as claimed in claim 19, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) preparing Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii), and
c) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Chlorpheniramine maleate coated granules.

30. The process for the preparation of extended-release suspension composition as claimed in claim 20, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) preparing Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the on the Phenylephrine hydrochloride-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii), and
c) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Phenylephrine hydrochloride coated granules.

31. The process for the preparation of extended-release suspension composition as claimed in claim 21, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) preparing Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) preparing Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii), and
d) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Chlorpheniramine maleate coated granules.

32. The process for the preparation of extended-release suspension composition as claimed in claim 22, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) preparing Phenylephrine Hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) preparing Phenylephrine hydrochloride particulate matrix comprising Phenylephrine Hydrochloride-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Phenylephrine Hydrochloride-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii), and
d) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Phenylephrine hydrochloride coated granules.

33. The process for the preparation of extended-release suspension composition as claimed in claim 23, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) preparing uncoated Chlorpheniramine maleate-sodium polystyrene sulfonate complex, and
d) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Chlorpheniramine maleate coated granules.

34. The process for the preparation of extended-release suspension composition as claimed in claim 24, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) preparing uncoated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex, and
d) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Chlorpheniramine maleate coated granules.

35. The process for the preparation of extended-release suspension composition as claimed in claim 25, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) preparing coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) preparing Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii),
d) preparing uncoated Chlorpheniramine maleate-sodium polystyrene sulfonate complex, and
e) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Chlorpheniramine maleate coated granules.

36. The process for the preparation of extended-release suspension composition as claimed in claim 26, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) preparing Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) preparing Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the on the Phenylephrine Hydrochloride-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii), and
d) preparing uncoated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex, and
e) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Phenylephrine hydrochloride coated granules.

37. The process for the preparation of extended-release suspension composition as claimed in claim 27, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) preparing Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Phenylephrine Hydrochloride-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii), and
c) preparing coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex comprising:
(i) preparing Chlorpheniramine maleate particulate matrix comprising Chlorpheniramine maleate-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Chlorpheniramine maleate-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Chlorpheniramine maleate-sodium polystyrene sulfonate complex obtained in step (ii), and
d) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Phenylephrine hydrochloride coated granules.

38. The process for the preparation of extended-release suspension composition as claimed in claim 28, wherein said process comprises:
a) preparing polymeric coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex comprising:
(i) preparing Dextromethorphan hydrobromide particulate matrix comprising Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex obtained in step (ii),
b) preparing uncoated Dextromethorphan hydrobromide-sodium polystyrene sulfonate complex,
c) preparing Phenylephrine hydrochloride-sodium polystyrene sulfonate complex comprising:
(i) preparing Phenylephrine hydrochloride particulate matrix comprising Phenylephrine hydrochloride-sodium polystyrene sulfonate,
(ii) coating with polyethylene glycol, isopropyl alcohol and purified water solution on the Phenylephrine Hydrochloride-sodium polystyrene sulfonate complex,
(iii) coating with functional barrier coating comprising ethyl cellulose, hydroxypropyl methylcellulose, dibutyl sebacate, talc, isopropyl alcohol and purified water on the pre-coated Phenylephrine hydrochloride-sodium polystyrene sulfonate complex obtained in step (ii),
d) preparing uncoated Chlorpheniramine maleate-sodium polystyrene sulfonate complex, and
e) preparing suspension adding microcrystalline cellulose and carboxymethylcellulose sodium (Avicel RC 591), sucrose, glycerin, methylparaben, propylparaben, citric acid, high fructose corn syrup, xanthan gum, suitable flavor and purified water to Dextromethorphan hydrobromide coated granules and Phenylephrine hydrochloride coated granules.

Dated this Twenty Sixth (26th) day of October, 2022.

_________________________________________
Dr. S. Padmaja
Agent for the Applicant
IN/PA/883