Description:FIELD OF THE INVENTION
The present invention relates to a Taste Masked Stable Pharmaceutical composition comprising of a Drug Resin complex. The present invention relates to a Taste Masked Stable Pharmaceutical composition comprising of a Drug Resin complex wherein the drug includes Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride, and wherein the resin includes atleast one ion exchange resin. The present invention relates to a Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the drug includes effective amount of Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride, and wherein the resin includes atleast one ion exchange resin. The present invention particularly relates to an immediate release Taste Masked Stable Orally Disintegrating Tablet composition comprising of effective amount of Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride with atleast one ion exchange Resin, and at least one pharmaceutically acceptable excipient.

The invention also relates to a process for preparation of the Taste Masked Stable Pharmaceutical composition comprising effective amount of Drug Resin complex. The invention also relates to a process for preparation of the Taste Masked Stable Orally Disintegrating Tablet composition comprising effective amount of Drug Resin complex. The invention particularly relates to the process for preparation of the Taste Masked Stable Orally Disintegrating Tablet composition comprising effective amount of Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride with atleast one ion exchange resin by Drug ion resin complexation process.

BACKGROUND OF THE INVENTION
Oral drug administration is the most convenient and common way to take pharmaceutical medications and various forms of oral administration which are available that includes solid tablets and capsules, powders, granules, syrups, suspensions and, more recently, chewable tablets and gummies. The oral route is the most convenient and usually the safest and least expensive route which is almost preferred. Even though oral formulations represent about 90% of the global market share of all drug formulations, they have some drawbacks. [ M.S. Alqahtani, et al., “Advances in Oral Drug Delivery,” Frontiers in Pharmacology (2021)]. Although most individuals use oral medicines, APIs which have a very bitter taste inhibits patient compliance. In 1979, the Johns Hopkins University defined patient compliance as related to “the extent to which a person’s behaviour (in terms of taking medications, following diets, or executing lifestyle changes) coincides with medical or health advice.” [Haynes RB. Introduction. In: Haynes RB, Taylor DW, Sackett DL, eds. Compliance in Health Care. Baltimore, MD: Johns Hopkins University Press]. Patient compliance is closely related to the acceptance of the medication. Many factors negatively impact patient compliance, but one of the biggest and yet most often overlooked is the taste of the medication. Bitterness reduction and inhibition are important characteristics of a good oral dosage form. Taste plays an especially important role in paediatric medications as well as adult compliance.

With respect to over-the-counter (OTC) preparations, such as cough and cold syrups, the bitterness of the preparation leads to lack of patient compliance. There are numerous pharmaceutical and OTC preparations that contain Dextromethorphan Hydrobromide, Chlorpheniramine etc, the expectorant guaifenesin, the decongestant pseudoephedrine as active which is bitter in taste. Dextromethorphan Hydrobromide is an antitussive used in much over-the-counter cold medication. Dextromethorphan hydrobromide is a cough suppressant, which relieves cough by decreasing the activity of cough centre in the brain. Chlorpheniramine Maleate is H1 antagonist used in allergic reactions, hay fever, rhinitis, urticarial and asthma. Moreover, Phenylephrine is used to relieve nasal discomfort caused by colds, allergies, and hay fever. It is also used to relieve sinus congestion and pressure. All these drugs are essential for nasal decongestion however its bitter taste makes the formulation unpalatable. Many of these bitter-tasting agents are pharmaceuticals which are found in liquid compositions (such as solutions and syrups), solid compositions (such as capsules and tablets), and more recently, dissolvable films. Hence, masking bitter taste of drugs to make the oral formulation acceptable to the patient is essential and efforts are made to provide a patient compliant product.

Bitter drugs can often be delivered intravenously or swallowed as a coated tablet, preventing stimulation of oral chemoreceptors so that the bitterness is not perceived. Various techniques available for masking bitter taste of drugs include taste masking with ingredients such as flavors, sweeteners, and amino acids; taste masking by polymer coating; taste masking by conventional granulation; taste masking by spray congealing with lipids; taste masking by formation of inclusion complexes with cyclodextrins; taste masking by the freeze-drying process; taste masking by making multiple emulsions; and taste masking with gelatin, gelatinized starch, liposomes, lecithins or lecithin-like substances, surfactants, salts, or polymeric membranes are available.

Also, various patent and non-patent literature available for taste masking bitter drugs like Dextromethorphan, Chlorpheniramine and has been discussed.
WO2012063257A2 discloses sustained release beads which comprise coated drug-resin complexes comprising drug-resin complexes of at least one active agent and at least one ion-exchange resin; coated with at least one release modifier.

IN-DELNP-2008-08703A discloses a coated drug - ion exchange resin complex comprising a core composed of a drug complexed with a pharmaceutically acceptable ion-exchange resin is provided. The drug - ion exchange resin complex is in admixture with a release retardant. The coating contains a polyvinyl acetate polymer and a plasticizer. Methods of making and products containing this coated complex are described.

WO2009088385A1 provides methods for preparing pharmaceutical resin- complexed granules which are taste-masked or capable of providing modified release of a water-soluble drug comprising the steps of (a) dissolving a water-soluble drug in water to form a solution; and (b) granulating the drug solution from step (a) in the presence of a resin capable of complexing with the drug to form a drug-resin complex.

The patent documents disclose different approaches wherein bitter taste of drug is masked by coating the drug resin complex and release of drug is modified to alter its release on tongue. However, this process known in the art provides sustained release of drugs prohibiting its interaction with taste buds and hence are palatable. Moreover, the process employed in taste masking are costly and have difficulty in scale up.

Thus, considering the disclosures in the art, the inventors of the present invention considered masking bitter taste of drugs by simple scalable process wherein the drug is formulated in an orally dispersible tablet and orally disintegrating tablet form. Inspite of immediate release of bitter drugs from the orally disintegrating tablet formulation, the inventors have been successful in masking the bitter taste of drugs by novel drug resin complex formation and providing a more patient compliant product. Hence, the inventors of the present invention formulated a stable taste masked orally Disintegrating formulation comprising of Drug resin complex wherein the drug comprises of effective amount of Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride and resin which includes atleast one ion exchange resin by a simple scalable process which provides a product which is patient compliant.

To summarize, the inventors of the present invention formulated a Taste Masked Stable Pharmaceutical composition comprising of a Drug Resin complex wherein the drug includes Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride, and wherein the resin includes atleast one ion exchange resin with atleast one pharmaceutically acceptable excipient which provides higher loading of drug in drug resin complex, immediate release of drug and mask bitter taste of drugs which improves patient compliance.

OBJECTIVE OF THE INVENTION
An objective of the invention is to design and develop taste masked orally Disintegrating Tablet for bitter drugs such as Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride.

Yet another object of the present invention is to provide taste masked orally Disintegrating Tablet for bitter drugs such as Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride by Drug Resin complexation process and process of preparation thereof.

Yet another object of the present invention to provide taste masked orally Disintegrating Tablet formulation for bitter drugs such as Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride by forming complex with Ion exchange Resin which is stable with higher drug loading, simple scalable process, provide immediate release, mask bitter taste, palatable which help improve patient compliance.

SUMMARY OF THE INVENTION
The present invention relates to a Taste Masked Stable Pharmaceutical composition comprising of a Drug Resin complex. The present invention relates to a Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the drug includes Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride and atleast one ion exchange resin. The present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the drug includes effective amount of Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride and atleast one ion exchange resin with atleast one pharmaceutically acceptable excipient.

The present invention particularly relates to an immediate release Taste Masked Stable Orally Disintegrating Tablet composition comprising of Drug Resin complex wherein the drug resin complex includes Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride, with atleast one ion exchange resin and at least one pharmaceutically acceptable excipient.

The invention also relates to the process for preparation of the Taste Masked Stable Orally Disintegrating Tablet composition comprising effective amount of Drug Resin complex. The invention particularly relates to the process for preparation of the Taste Masked Stable Orally Disintegrating Tablet composition comprising effective amount of Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride with atleast one ion exchange resin by Drug ion resin complexation process.

DETAILED DESCRIPTION OF THE INVENTION

In describing the embodiment of the invention, specific terminology is chosen for the sake of clarity. However, it is not intended that the invention be limited to the specific terms so selected and it is to be understood that such specific terms include all technical equivalents that operate in a similar manner to accomplish a similar purpose. As used herein, reference to an element by the indefinite article “a” or “an” does not exclude the possibility that more than one of the elements is present, unless the context clearly requires that there is one and only one of the elements. The disclosure of numerical ranges should be understood as referring to each discrete point within the range, inclusive of endpoints, unless otherwise noted. The term “about” as used in the disclosure of numerical ranges indicates that deviation from the stated value is acceptable to the extent that the deviation is the result of measurement variability and/or yields a product of the same or similar properties.

As used herein the term “taste masked” is defined as a perceived reduction of an undesirable taste that would otherwise exist. Taste masking results in formation of a physical barrier between drug particle and the taste bud which minimizes the interaction and making the bitter drug palatable.

The embodiments of the present invention directed for Orally disintegrable Tablet formulation are also applicable to Orally dispersible Tablet formulation.

The present invention relates to a Taste Masked Stable Pharmaceutical composition comprising of a Drug Resin complex. The present invention relates to a Taste Masked Stable Orally Disintegrating or Dispersible Tablet composition comprising of a Drug Resin complex.

According to an embodiment, the present invention relates to a Taste Masked Stable Pharmaceutical composition comprising of a Drug Resin complex wherein the composition is orally dispersible tablet or orally disintegrating tablet.

According to an embodiment, the present invention relates to Taste Masked Stable Pharmaceutical composition comprising of a Drug Resin complex wherein the drug includes Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride.

According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the drug includes Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride.

According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Dispersible Tablet composition comprising of a Drug Resin complex wherein the drug includes Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride.

According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the drug includes effective amount of Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride.

According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the drug includes effective amount of Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride with atleast one ion exchange resin and at least one pharmaceutically acceptable excipient.

According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Dispersible Tablet composition comprising of a Drug Resin complex wherein the drug includes effective amount of Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride with atleast one ion exchange resin and at least one pharmaceutically acceptable excipient.

According to an embodiment, the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention wherein the drug includes Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride.

According to an embodiment, the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention wherein the drug includes effective amount of Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride. According to an embodiment, the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention wherein the drug includes Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride with concentration of atleast 4%. According to an embodiment, the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention wherein the drug includes Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride with concentration of atleast 3%. According to an embodiment, the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention wherein the drug includes Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride with concentration of atleast 2%.

According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the resin includes atleast one ion exchange resin.

According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the resin includes Methacrylic acid divinyl benzene copolymer with Hydrogen lon, Polacrilin potassium, Calcium Polystyrene Sulphate, Sodium Polystyrene Sulphate. However, those skilled in the art will appreciate that it is possible to utilize other resins without departing from the scope of the present invention. According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the resin particularly includes Methacrylic acid divinyl benzene copolymer with hydrogen ion.

According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the resin is present in an effective amount.

According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the Drug Resin complex is uncoated.

According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the ratio of drug resin complex is in the range of 1:4. According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the ratio of drug resin complex is in the range of 1:3. According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the ratio of drug resin complex is in the range of 1:2. According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the ratio of drug resin complex is in the range of 1:2.5. According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the ratio of drug resin complex is in the range of 1:1. According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition comprising of a Drug Resin complex wherein the ratio of drug resin complex particularly is in the range of about 1:2, 1:2.5 and 1:3.

According to a further embodiment, the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention further include at least one pharmaceutically acceptable excipients such as diluents, binders, superdisintegrants, disintegrant, sweeteners, flavouring agent, lubricant, vehicle, colouring agent, glidant.

According to an embodiment the disintegrant or super-disintegrant include atleast one of Sodium starch glycolate, Croscarmellose sodium, Crospovidone. However, those skilled in the art will appreciate that it is possible to utilize other disintegrant or super-disintegrant without departing from the scope of the present invention.

According to an embodiment the diluents include atleast one of Lactose, Fructose, Sorbitol powder and Mannitol. However, those skilled in the art will appreciate that it is possible to utilize other diluents without departing from the scope of the present invention.

According to an embodiment the binders include atleast one of Polyvinylpyrrolidone K90, Pregelatinized starch, Starch, Hydroxy Propyl Cellulose and Purified water. However, those skilled in the art will appreciate that it is possible to utilize other binders without departing from the scope of the present invention.

According to an embodiment the flavorants or flavouring agents include atleast one of Mango flavour, Orange flavour, Pineapple flavour, Banana flavour, Masking flavour and Peppermint flavour. However, those skilled in the art will appreciate that it is possible to utilize other flavorants or flavouring agents without departing from the scope of the present invention.

According to an embodiment the sweeteners include atleast one of Aspartame, Sucralose, Saccharine Sodium and Neotame However, those skilled in the art will appreciate that it is possible to utilize other sweeteners without departing from the scope of the present invention.

According to an embodiment the lubricants include atleast one of Magnesium Stearate, Stearic Acid, Hydrogenated Castor Oil and Sodium Stearyl Fumarate. However, those skilled in the art will appreciate that it is possible to utilize other lubricants without departing from the scope of the present invention.

According to an embodiment, the disintegration time of the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention is about 10 seconds to 40 seconds. According to an embodiment, the disintegration time of the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention is about 10 seconds to 20 seconds. According to an embodiment, the disintegration time of the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention is about 40 seconds. According to an embodiment, the disintegration time of the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention is about 35 seconds. According to an embodiment, the disintegration time of the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention is about 30 seconds. According to an embodiment, the disintegration time of the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention is about 20 seconds. According to an embodiment, the disintegration time of the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention is about 20 seconds. According to an embodiment, the disintegration time of the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention is about 15 seconds. The disintegration time is measured with Disintegration Test Apparatus namely Electrolab Disintegration Tester.
According to an embodiment, the hardness of the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention is in the range of 70N to 90N. According to an embodiment, the hardness of the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention is in the range of 75N to 85N. According to an embodiment, the hardness of the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention is in the range of 70N to 80N. The hardness is measured by using a Electrolab tablet hardness tester wherein crushing strengths of six randomly selected tablets were measured and expressed in Newton units.

According to an embodiment, the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention provides immediate release. According to a further embodiment, the release of drugs from Taste Masked Stable Orally Disintegrating Tablet composition of the present invention wherein alteast 90% of the drug is released within 10minutes. According to a further embodiment, the release of drugs from Taste Masked Stable Orally Disintegrating Tablet composition of the present invention wherein alteast 92% of the drug is released within 10minutes. According to a further embodiment, the release of drugs from Taste Masked Stable Orally Disintegrating Tablet composition of the present invention wherein alteast 95% of the drug is released within 10minutes. According to a further embodiment, the release of drugs from Taste Masked Stable Orally Disintegrating Tablet composition of the present invention wherein alteast 97% of the drug is released within 10minutes. According to a further embodiment, the release of drugs from Taste Masked Stable Orally Disintegrating Tablet composition of the present invention wherein alteast 98% of the drug is released within 10minutes. According to a further embodiment, the release of drugs from Taste Masked Stable Orally Disintegrating Tablet composition of the present invention wherein alteast 99% of the drug is released within 10minutes. According to a further embodiment, the release of drugs from Taste Masked Stable Orally Disintegrating Tablet composition of the present invention wherein alteast 100% of the drug is released within 10minutes.

According to an embodiment, the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention mask bitter taste of drug and provides sweet taste. According to an embodiment, the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention has at least about 40 percent better mouth-feel. According to an embodiment, the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention has at least about 50 percent better mouth-feel. According to an embodiment, the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention has at least about 70 percent better mouth-feel. According to an embodiment, the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention has at least about 80 percent better mouth-feel. According to an embodiment, the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention has at least about 90 percent better mouth-feel. According to an embodiment, the Taste Masked Stable Orally Disintegrating Tablet composition of the present invention has at least about 95 percent better mouth-feel.

According to a further embodiment, the present invention relates to the Taste Masked Stable Orally Disintegrating Tablet composition wherein the composition is stable. The stability test was done as per ICH guidelines and the composition has been tested at 40oC/75%RH for 6 months and at 30oC/75%RH.

According to an embodiment, the present invention relates to the process for preparation of the Taste Masked Stable Orally Disintegrating Tablet composition comprising effective amount of Drug Resin complex.

According to the further embodiment, the invention particularly relates to the process for preparation of the Taste Masked Stable Orally Disintegrating Tablet composition comprising effective amount of Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride with an ion exchange resin by Drug ion resin complexation process.

According to an embodiment, the present invention relates to a process of preparation of Taste Masked Stable Orally Disintegrating Tablet composition of the present invention includes:
Step 1: Heating Purified Water up to 70°C±5°C into stainless still vessel and keep the stirrer speed such that to form vortex in Purified Water. Further Add slowly Chlorpheniramine Maleate into hot purified water under continuous stirring to get clear solution followed by slow addition of Dextromethorphan Hydrobromide under continuous stirring. Further Slowly Methacrylic acid divinyl benzene copolymer with Hydrogen lon is also added continuous stirring wherein the stirring is continued for next 40-45 minutes
Step 2: Phenylephrine Hydrochloride under continuous stirring is added slowly to purified water to get clear solution.
Step 3: Sift atleast one excipient such as disintegrant, binder, diluent, glidant through sieve using sifter and transfer the sifted material to the High Shear Mixer Granulator and transfer the sifted colour & atleast one excipient to the Rapid Mixer Granulator (RMG). Mix the sifted material of High Shear Mixer Granulator for 10 minutes.
Step 4: Adding the Drug Solution into High Shear Mixer Granulator and mix for 5 minutes at slow speed. Further add the Drug-Resin Complex into mix material in High Shear Mixer Granulator and granulate till wet mass of desired consistency is formed. Also, additional quantity of Purified Water to be add to achieve the desired consistency of wet mass.
Step 5: Drying the wet granules at 60°C (± 5°C) in Fluid Bed Dryer to get LOD of dried granules between 2.0% - 3.0%w/w.
Step 6: Sift the dried granules through appropriate sieve using vibratory sifter and add flavour, masking flavor, atleast one lubricant to octagonal blender and mix for 5 minutes. Further, compress the lubricated granules using round shaped, flat faced beveled edged punches to obtain Orally Disintegrating Tablet of the present invention.

The inventors of the present invention found that the Taste masked orally Disintegrating Tablet composition of the present invention helps mask bitter taste of drugs by drug resin ion exchange complexation. The inventors of the present invention masked the bitter taste of drugs with the help of Drug -Resin complex wherein the drug resin complex is uncoated and helped to make the drugs like Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride palatable. Inspite of the immediate release of drugs from the Taste masked Orally Disintegrating Tablet composition of the present invention, the taste of the drugs was not bitter and thus added to patient compliance. Thus, Taste masked Orally Disintegrating Tablet composition of the present invention provide simple scalable process, immediate release, high drug loading, reduce dose frequency, masks bitter taste with pleasant mouth feel making it palatable and patient compliant.

Other embodiments of the present disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the disclosed embodiments. The following examples should be considered as exemplary only, with a true scope and spirit of the present disclosure being indicated by the claims. It will be understood that particular embodiments described herein are shown by way of illustration and not as limitations of the invention. The principal features of this invention can be employed in various embodiments without departing from the scope of the invention. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific procedures described herein. Such equivalents are considered to be within the scope of this invention and are covered by the claims. While the compositions and methods of this invention have been described in terms of embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be Substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.

Preparatory Examples:
Specific preferred embodiments of the invention will now be described with reference to the following examples which should be regarded in an illustrative rather than a restrictive sense.
Table 1
INGREDIENTS Example 1 Example 2 Example 3 Example 4 Example 5
1)Dextromethorphan Hydrobromide 12 10 9 10 12
2)Methacrylic acid divinyl benzene copolymer with Hydrogen lon 17 - 34 42.5 -
3) Calcium Polystyrene Sulphate - 25.5 - - -
4)Polacrilin potassium - - - - 51
5)Purified Water q.s. q.s. q.s. q.s. q.s.
6)Chlorpheniramine Maleate 2 1 3 2 1
7)Lactose - - - 116.5 -
8)Fructose - - - - 95.6
9)Mannitol 159 120.1 120.5 - -
10)Microcrystalline Cellulose 40 55 50 - -
11)Sorbitol powder - - - 55 60
12)Phenylephrine Hydrochloride 3 6 5 5 4
13)Colloidal Silicon Dioxide 4 2 3 4 3
14)Starch 15 25 20 20 15
15)Crospovidone 25 15 20 - -
16)Sodium Starch Glycollate - - - 30 25
17)Colour 1.5 0.9 1 1 0.9
18) Crospovidone 40 35 30 - -
19)Croscarmellose - - - 35 40
20) Colloidal Silicon Dioxide 1 2 3 3 1.5
21) Flavour (peppermint or strawberry or orange or mango) 2.5 4 3.50 3 2.5
22) Masking Flavour 2 1.5 1.50 2 1.5
23)Sucralose 3 2.0 2.50 3 2
24) Sodium Stearyl Fumarate - - - 8 10
25) Magnesium Stearate 8 10 9.00 - -
Physical Properties
Hardness (N) 75 85 90 70 80
Disintegration time (Seconds) 15 25 20 15 20
Average weight of tablet (mg) 425 425 425 425 425
Release in 10min (%)
Phenylephrine HCL 100.3 99.8 101.3 100 101
Chlorpheiramine maleate 90.9 94.3 95.4 91 96.5
Dextromorphan HCl 96.8 97.3 99.6 98.8 101
Friability 0.08 0.07 0.07 0.08 0.07
Bitter Taste Sweet with
40% better mouth feel Sweet
60% better mouth feel Sweet
80% better mouth feel
Sweet
80% better mouth feel Sweet
80% better mouth feel

Example 1 is prepared as follows:
Step 1: Heat the Purified Water up to 70°C±5°C and Start the stirrer & keep the stirrer speed such that to form vortex in Purified Water. Slowly added Chlorpheniramine Maleate into hot purified water under continuous stirring to get clear solution followed by addition of Dextromethorphan Hydrobromide under continuous stirring, Further, add slowly Methacrylic acid divinyl benzene copolymer with Hydrogen ion under continuous stirring which is continued for next 45 minutes
Step 2: Appropriate amount of Phenylephrine Hydrochloride under continuous stirring is added to water till to get a clear solution.
Step 3: Mannitol, Microcrystalline Cellulose, Crospovidone and Sucralose is sifted through 40# SS sieve using sifter which is then transferred to the High Shear Mixer Granulator. Further color is added to the High shear mixer granulator.
Step 4: Mixing the sifted material of High Shear Mixer Granulator for 10 minutes wherein the drug solution is added to the High Shear Mixer Granulator and the drug resin mass is granulated till wet mass of desired consistency is formed. Additional quantity of Purified Water was added to achieve the desired consistency of wet mass.
Step 5: Dry the wet granules at 60°C (± 5°C) in Fluid Bed Dryer to get LOD of dried granules between 2.0% - 3.0%w/w and sift the dried granules through 40# SS sieve using vibratory sifter.
Step 6: Sifted Flavour, Masking Flavour, Sucralose, Crospovidone & Colloidal Silicon Dioxide through 40# SS sieve and also sifted Magnesium Stearate through 100# SS sieve. Transfer dried and sized granules along with lubricants to the blender and mix for 20 minutes at 8 RPM. Further, compress the lubricated granules using round shaped, flat faced beveled edged punches to obtain Orally Disintegrating Tablet of the present invention.

Example 2 and 3 are prepared as per the process mentioned in Example 1. The samples prepared as per Example 1, 2 and 3 were tested for stability as per ICH guidelines and the data for the same is mentioned in Table 2-4. Also, physical properties of samples prepared as per Example 1-5 such as hardness, tablet weight, friability, dissolution profile were tested and mentioned in Table 1. The bitter taste of ODT formulation as mentioned in Example 1-5 were tested on 10 volunteers and the taste of drug was determined on their response which is as presented in the Table 1.The dissolution test of formulation of the present invention exemplified in examples 1-5 were evaluated by USP paddle method in 0.1N HCl as dissolution media at 10, 15, 20, 30 and 45 minutes respectively. The dissolution data at different time intervals in presented in Table 5

Table 2: Stability Data for Example 1
EXAMPLE 1
Tests Limits Initial 30°C/75%RH 40°C/75%RH
3M 6 M 9 M 12 M 3M 6M
Disintegration Time NMT 180 Sec 15-25 sec 14-19 sec 15-18sec 15-20 sec 12-20 sec 20-25 sec 16-20 sec
UOD To comply Complies Complies Complies Complies Complies Complies Complies
Dissolution
Phenylephrine Hydrochloride NLT 70 % 103.3 103.6 101.8 101.5 99.1 101.5 98.9
Chlorpheniramine Maleate NLT 70 % 100.3 100.3 97.4 98.6 100.4 99.8 94.1
Dextromethorphan Hydrobromide NLT 70 % 98.8 99.9 97.4 99.2 99.3 99.9 93.3
Assay
Phenylephrine Hydrochloride 90-110% 106.31 104.06 104.35 103.24 102.27 101.50 102.02
Chlorpheniramine Maleate 90-110% 105.50 102.25 103.11 102.87 102.28 102.31 101.89
Dextromethorphan Hydrobromide 90-110% 105.27 104.35 103.17 103.56 102.29 102.90 103.37
Microbiological Tests
Total Bacterial Count NMT200 cfu/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g
Total Fungal Count NMT20 cfu/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g
Pathogens Absent/g Absent/g Absent/g Absent/g Absent/g Absent/g Absent/g Absent/g

Table 3: Stability Data for Example 2
EXAMPLE 2
Tests Limits Initial 30°C/75%RH 40°C/75%RH
3M 6 M 9 M 12 M 3M 6M
Disintegration Time NMT 180 Sec 22-25 sec 15-21 sec 15-22 sec 15-20 sec 18-20 sec 15-23sec 17-29 sec
UOD To comply. Complies Complies Complies Complies Complies Complies Complies
Dissolution
Phenylephrine Hydrochloride NLT 70 % 101.3 104.2 102.0 101.5 97.9 101.2 98.8
Chlorpheniramine Maleate NLT 70 % 99.1 102.8 97.4 98.2 98.7 99.8 94.7
Dextromethorphan Hydrobromide NLT 70 % 98.2 103.6 97.3 98.6 97.9 100.4 93.2
Assay
Phenylephrine Hydrochloride 90-110% 105.93 104.10 103.96 102.05 101.79 101.50 102.25
Chlorpheniramine Maleate 90-110% 105.13 102.02 102.56 102.89 102.71 102.49 102.05
Dextromethorphan Hydrobromide 90-110% 104.13 104.12 104.02 103.95 103.54 102.92 103.35
Microbiological Tests
Total Bacterial Count NMT200 cfu/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g
Total Fungal Count NMT20 cfu/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g
Pathogens Absent/g Absent/g Absent/g Absent/g Absent/g Absent/g Absent/g Absent/g

Table 4: Stability Data for Example 3

EXAMPLE 3
Tests Limits Initial 30°C/75%RH 40°C/75%RH
3M 6 M 9 M 12 M 3M 6M
*Description To Complies Complies Complies Complies Complies Complies Complies Complies
Disintegration Time NMT 180 Sec 22-25 sec 15-20 sec 13-21 sec 16-21 sec 15-20sec 15-26 sec 17-28 sec
UOD To comply. Complies Complies Complies Complies Complies Complies Complies
Dissolution
Phenylephrine Hydrochloride NLT 70 % 101.4 103.3 102.1 101.5 97.9 103.0 98.6
Chlorpheniramine Maleate NLT 70 % 100.1 100.6 96.9 98.6 99.7 102.9 94.0
Dextromethorphan Hydrobromide NLT 70 % 100.3 101.8 97.6 98.3 98.8 103.7 93.3
Assay
Phenylephrine Hydrochloride 90-110% 105.61 104.01 103.75 102.87 101.82 102.22 102.15
Chlorpheniramine Maleate 90-110% 103.07 102.38 102.92 103.06 103.26 102.29 102.12
Dextromethorphan Hydrobromide 90-110% 103.61 103.19 103.43 103.15 103.26 102.12 102.90
Microbiological Tests
Total Bacterial Count NMT200 cfu/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g
Total Fungal Count NMT20 cfu/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g <10CFU/g
Pathogens Absent/g Absent/g Absent/g Absent/g Absent/g Absent/g Absent/g Absent/g
Thus, the data indicated in Table 2-4 demonstrates that the composition of the present invention is stable.

Table 5: Dissolution Data
Table 5a: Dissolution data for drug Phenylephrine HCl
Drug: Phenylephrine HCl Dissolution media: 0.1N HCl
RPM: 75
Apparatus: USP Paddle
Dissolution media: pH 6.8
RPM: 75
Apparatus: USP Paddle

% Release % Release
Time (minutes) 10min 15min 20 min 30min 45min 10min9 15 min 20 min 30min 45min
Example 1 100.3 99.8 97.2 96.8 95.2 100.5 98.6 96.8 94.7 91.4
Example 2 99.8 99.2 99.3 97.6 94.7 99.5 98.3 95.8 93.9 90
Example 3 101.3 100.8 99.9 97.8 97 101.8 100.6 100.6 96.2 91.6
Example 4 100.9 100.3 98.4 97 96.2 100.9 99.1 99.1 93.9 90.3
Example 5 101.1 100.5 99.2 96.5 95.3 100.5 99.4 99.4 94.8 90.7

Table 5b: Dissolution data for drug Chlorpheniramine Maleate
Drug: Chlorpheniramine Maleate
Dissolution media: 0.1N HCl
RPM: 75
Apparatus: USP Paddle
Dissolution media: pH 6.8
RPM: 75
Apparatus: USP Paddle

% Release % Release
Time (minutes) 10min 15min 20 min 30min 45min 10min9 15 min 20 min 30min 45min
Example 1 90.9 93.9 93.1 90.7 90.3 90 91.8 89.7 91.4 89.4
Example 2 94.3 94.1 92.7 90.7 88.2 92.4 95.1 89.6 88.8 87.9
Example 3 95.4 94 94.1 90.1 88.6 94.9 98.3 98.2 92 91.5
Example 4 91 92.3 92.3 92 88.4 87.9 95.4 89.7 87.8 87.8
Example 5 96.5 93.7 92.5 89.9 85.5 95.4 93.6 91.5 91.5 91.8

Table 5c: Dissolution data for drug Dextromethorphan Hydrobromide
Drug: Dextromethorphan HBr
Dissolution media: 0.1N HCl
RPM: 75
Apparatus: USP Paddle
Dissolution media: pH 6.8
RPM: 75
Apparatus: USP Paddle

% Release % Release
Time (minutes) 10min 15min 20 min 30min 45min 10min9 15 min 20 min 30min 45min
Example 1 96.8 95.5 96.4 94.6 92 92.5 93.4 91.8 91.4 86.5
Example 2 97.3 97 96.4 94.3 96.9 93.5 92.5 91.8 88.9 87.9
Example 3 99.6 99.2 96.9 96.2 94.6 94.7 96.6 93.4 91.6 88.9
Example 4 98.8 97.6 96.2 94.5 93.3 91.7 92.9 92.2 90.6 84.9
Example 5 101 99.7 99.8 95.2 94.3 92.5 92.5 91.8 90 86.8
Thus, the data indicated in Table 5 demonstrates that the composition of the present invention depicts immediate release of drugs in different media. Thus, the stable taste masked Orally Disintegrating Tablet composition of the present invention demonstrates immediate release which is atleast 90% of the drug release in 10minutes.

Moreover, the inventors of the present invention further demonstrated the bitter taste of drugs of different formulations on Taste Panel members which were chosen among male and female candidates for their ability to distinguish flavours, sweetness and mouth feel and were trained in how to score different characteristics. Approx. 2 ml of each Test sample consumed in interval of 5 minutes and a pinch of coffee followed by water is consumed between 2 testing intervals to diminish the taste effect of previous test sample. The volunteers determined the score on their taste and data of same is mentioned in Table 6. The scoring criteria is as mentioned below:
Overall taste Scale Flavour Scale Sweetness Scale
Unpalatable 0-0.5 Unpleasant 0-0.5 Bitter 0-0.5
Palatable 0.6-1.9 Mild 0.6-1.9 Palatable 0.6-1.9
Good 2-2.5 Pleasant 2-2.5 Moderately sweet 2-2.5
Excellent 2.6-3.0 Excellent 2.6-3.0 Sweet 2.6-3.0

Table 6:
Overall taste Flavor Sweetness
Volunteer name Tablet with Drug to Resin ratio of 1:1.5 Tablet with Drug to Resin ratio of 1:2.0 Tablet with Drug to Resin ratio of 1:2.5 Tablet with Drug to Resin ratio of 1:1.5 Tablet with Drug to Resin ratio of 1:2.0 Tablet with Drug to Resin ratio of 1:2.5 Tablet with Drug to Resin ratio of 1:1.5 Tablet with Drug to Resin ratio of 1:2.0 Tablet with Drug to Resin ratio of 1:2.5
YGA (M) 2.10 2.70 2.70 2.00 2.70 2.70 2.00 2.70 2.10
ALC (M) 2.00 2.80 2.80 2.00 2.80 2.80 2.00 2.80 2.00
AKP (M) 2.30 3.00 3.00 2.40 3.00 3.00 2.40 3.00 2.30
DRD (M) 2.10 2.70 2.70 2.20 2.60 2.60 1.90 2.50 2.10
ASA (M) 2.00 2.50 2.50 2.00 2.50 2.50 2.00 2.50 2.00
KVD (F) 2.10 2.70 2.70 2.00 2.70 2.70 2.00 2.70 2.10
SRD (M) 2.10 2.70 2.70 2.00 2.70 2.70 2.00 2.70 2.10
DVJ (M) 2.30 2.90 2.90 2.40 3.00 3.00 2.40 3.00 2.30
AKL (M) 2.30 3.00 3.00 2.40 3.00 3.00 2.40 2.90 2.30
NVT (M) 2.30 2.70 2.70 2.00 2.60 2.60 2.00 2.70 2.30
VUB (M) 1.50 2.50 2.50 1.90 2.60 2.60 2.30 2.50 1.50
MDN (M) 2.10 2.70 2.70 2.00 2.70 2.70 2.00 2.70 2.10
KR (M) 2.30 3.00 3.00 2.20 2.80 2.80 2.30 2.50 2.30
SSP (F) 1.90 3.00 2.90 2.20 3.00 3.00 2.10 3.00 1.90
Total score 29.40 38.90 38.80 29.70 38.70 38.70 29.80 38.20 38.10
Average score 2.1 2.77 2.77 2.12 2.76 2.76 2.1 2.72 2.72
Thus, data indicated in Table 6 indicates that the composition of the present invention has overall excellent taste inspite of immediate release of drugs from the formulation.

Technical Advancements:
The present disclosure described herein above has several technical advantages including, but not limited to, the realization of:
?Mask bitter taste
?Immediate drug release
?Drug resin complex is uncoated
?Dose reduction and dosing frequency reduction
?Scalable process
?Patient compliant , Claims:WE CLAIM:
1.A taste-masked Orally Disintegrating Tablet pharmaceutical composition comprising: a drug-resin complex; wherein
the drug includes Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride; and
resin includes atleast one ion exchange resin.
2.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein the drug resin complex is uncoated.
3.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein the drug resin ratio is about 1:3, particularly about 1:2.5, particularly about 1:2 and 1:1.
4.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein resin includes Methacrylic acid divinyl benzene copolymer with Hydrogen lon, Polacrilin potassium, Calcium Polystyrene Sulphate, Sodium Polystyrene Sulphate.
5.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein resin particularly includes Methacrylic acid divinyl benzene copolymer with Hydrogen lon.
6.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein the drug resin complex includes Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride present in a concentration of atleast 4%.
7.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, further includes atleast one pharmaceutically acceptable excipient.
8.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein atleast one pharmaceutically acceptable excipient comprises atleast one diluent, disintegrant, super-disintegrants, binders, diluents, lubricants, flavouring agent, sweeteners, colorants, or combinations and mixtures thereof.
9.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein disintegrants include atleast one of Sodium starch glycolate, Croscarmellose sodium, Crospovidone.
10.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein diluents include atleast one of Lactose, Fructose, Sorbitol Powder, and Mannitol.
11.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein the binders include atleast one of Polyvinylpyrrolidone K90, Pregelatinized starch, Starch, Hydroxy Propyl Cellulose and Purified water.
12.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein flavorants or flavouring agents include atleast one of Mango Flavour, Orange Flavour, Pineapple Flavour, Banana Flavour, Masking Flavour and Peppermint Flavour.
13.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein the sweeteners include atleast one of Aspartame, Sucralose, Saccharine Sodium, and Neotame.
14.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein the lubricants include atleast one of Magnesium Stearate, Stearic Acid, Hydrogenated Castor Oil and Sodium Stearyl Fumarate.
15.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein the composition provides immediate release.
16.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein the composition provides atleast 90% release of drugs in 10 minutes.
17.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein the composition comprises a disintegration time of about 15 seconds to about 40 seconds.
18.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein the composition comprises a hardness of between about 70 N to about 90N
19.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein the composition has at least about 40 percent better mouth-feel.
20.The taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, wherein the composition effectively masks an unpalatable taste associated with immediate delivery of the drugs.
21.A process of preparing taste-masked Orally Disintegrating pharmaceutical composition as claimed in claim 1, by Drug ion resin complexation process includes:
Step 1: Heating Purified Water up to 70°C±5°C into stainless still vessel and keep the stirrer speed such that to form vortex in Purified Water. Further add slowly Chlorpheniramine Maleate into hot purified water under continuous stirring to get clear solution followed by slow addition of Dextromethorphan Hydrobromide under continuous stirring. Further Slowly Methacrylic acid divinyl benzene copolymer with Hydrogen lon is also added continuous stirring wherein the stirring is continued for next 40-45 minutes
Step 2: Phenylephrine Hydrochloride under continuous stirring is added slowly to purified water to get clear solution.
Step 3: Sift atleast one excipient such as disintegrant, binder, diluent etc through sieve using sifter and transfer the sifted material to the High Shear Mixer Granulator and transfer the sifted colour & atleast one excipient to the Rapid Mixer Granulator (RMG). Mix the sifted material of High Shear Mixer Granulator for 10 minutes.
Step 4: Adding the Drug Solution into High Shear Mixer Granulator and mix for 5 minutes at slow speed. Further add the Drug-Resin Complex into mix material in High Shear Mixer Granulator and granulate till wet mass of desired consistency is formed. Also, additional quantity of Purified Water to be add to achieve the desired consistency of wet mass.
Step 5: Drying the wet granules at 60°C (± 5°C) in Fluid Bed Dryer to get LOD of dried granules between 2.0% - 3.0%w/w.
Step 6: Sift the dried granules through appropriate sieve using vibratory sifter and add flavour, masking flavour, atleast one lubricant to octagonal blender and mix for 5 minutes. Further, compress the lubricated granules using round shaped, flat faced beveled edged punches to obtain Orally Disintegrating Tablet of the present invention.
The method of masking bitter taste of drugs by taste-masked Orally Disintegrating Tablet pharmaceutical composition comprising of a drug-resin complex, wherein the drug includes Dextromethorphan Hydrobromide, Chlorpheniramine Maleate and Phenylephrine Hydrochloride; and resin includes atleast one ion exchange resin as claimed in claim 1.