DESC:FIELD OF THE INVENTION
The present invention relates to a cost effective, single pot process for synthesis of sustained release composition. The present invention further relates to the process of preparation of drug-resin complexes in slurry form in a single pot. In particular, the present invention is related to the process of preparation of sugar free, Dextromethorphan HBr and Chlorpheniramine Maleate in a single pot for sustained release composition.

BACKGROUND OF THE INVENTION
Dextromethorphan is a cough suppressant and one of the most widely used antitussives for the treatment of cough associated with acute upper respiratory tract infection. It acts centrally to relieve cough, is active against dry cough. The maximum time of effectiveness of dextromethorphan in conventional compositions is only a few hours due to its short half –life of 1.2 to 3.9 hours which requires repeated dosages at frequent intervals to obtain long term therapeutic levels of drug.

Chlorpheniramine belongs to the class of antihistamines and works by blocking the H1 receptors. It helps to control the symptoms of cold or allergies. Chlorpheniramine is often combined with cough suppressant dextromethorphan and which is available in the market as Coricidin and other brands.

Multiple dosing often results in poor patient compliance and inefficient therapy. Hence, development of sustained release formulation of active agents that release the drug at a predetermined rate to maintain a desired therapeutic effect over a comparatively longer period of time with reduced side effects are particularly desirable.

Various attempts have been made in the art to provide sustained release compositions of active ingredients comprising a mixture of coated drug-resin complexes. Suspension dosage forms comprising either completely coated drug-resin complexes coated at a single level or comprising a portion of un-coated and a portion of coated drug-resin complexes have been described therein. The preparation process of coated drug-resin complexes involves multiple steps of granulation, drying, coating with rate controlling polymer thereby increasing the cost of the process. Moreover, the use of plasticizers in certain processes impacts the flexibility of the drug-resin complex granules.

The present inventors felt that there is a scope in the art to provide cost effective, industrially viable process for preparation of sugar free, uncoated drug–resin complexes for sustained release composition which remains the objective of the invention.

SUMMARY OF THE INVENTION
In accordance with the above, the present invention provides a cost effective, single pot process for preparation of sugar free sustained release composition, wherein the process comprises preparation of drug-resin complexes in slurry form in a single pot. The drug resin complexes in the slurry form are uncoated drug resin complexes which are added in to the liquid vehicle to obtain the desired sustained release composition.

In an aspect, the present invention provides a cost effective, single pot process for the preparation of sugar free sustained release composition comprising;
i. Preparing the wet slurry of drug–resin in a single pot by dispersing insoluble polymer cation exchange resin in purified water and stirring, followed by dispersing in parts the first active ingredient and stirring continuously for a given time interval to obtain the slurry containing the first active-resin complex, the unbound first active and unbound resin;
ii. Dispersing in parts the second active ingredient to the above slurry in said pot with continuous stirring until formation of second active-resin complex with the unbound resin in the slurry form and the unbound second active ;
iii. Adding non-crystallized sweetener to the above mixture in said pot and stirring to get the homogenized slurry under close conditions;
iv. Homogenizing the slurry of step iii into a slurry of suitable food additives/ viscosifiers and preservatives dissolved in polyol followed by addition of pharmaceutically acceptable excipients, non-crystallized sweeteners, optionally pH adjuster in steam jacketed manufacturing vessel and making up to the final volume with purified water to obtain the composition.

In an aspect, the percentage of the actives bound to the resin in the slurry is NLT 85%.

In another aspect, the percentage of the first active ingredient bound to the resin is about 90.50% and the percentage of the second active ingredient bound to the resin is about 87.80%.

The process of the present invention is carried out at a temperature in the range of 25-45°C.

The first active ingredient is selected from Dextromethorphan HBr in an amount of 0.6%w/v to 1.8%w/v in the in-situ drug resin complex.

The second active ingredient is selected from Chlorpheniramine Maleate in an amount of 0.08%w/v to 0.16% w/v in the in-situ drug resin complex.

The polymer cation exchange resin is preferably selected from Sodium polystyrene sulfonate (Polistirex) in an amount of 0.6% w/v-5.4%w/w/v of the drug in the in-situ drug resin complex.

The sweetener is selected from natural high intensity sweetener such as stevia, sorbitol, sucralose, aspartame, saccharin and the like in an amount of 0.001 to 50%w/v. The use of natural high intensity sweetener in the present composition makes it consumer friendly and can be given to patients having high glycemic index with no adverse effects.

The food additive/viscosifier is selected from xanthan gum, arabic gum, guar gum and the like in an amount of 0.001 to 50%w/v, preferably xanthan gum in an amount of 0.5%w/v.

The polyol is selected from propylene glycol in an amount of 1% to 30%w/v.

The pharmaceutically acceptable excipients are selected from carriers, diluents, preservatives, surfactants/suspending agents, emulsifiers, colorants, flavorants, pH adjusters and the like in an amount of 0.001 to 30%w/v.

The preservatives are selected from Methyl Hydroxybenzoate, Propyl Hydroxybenzoate and the like in an amount of 0.01 to 2%w/v.

The surfactant is selected from non-ionic surfactant such as polysorbate 80, poloxamer, polysorbate 20 and the like in an amount of 1-2%w/v. Preferably, the surfactant is polysirbate 80.

The pH adjuster is selected from anhydrous citric acid or its salt.

The final sustained release composition is free of natural sugar, any coating material and is free of lumps and therefore the need to store at lower temperature is not required.

In an aspect, the process of the present invention can be scaled up to industrial level.

In a preferred aspect, the present invention provides a cost effective, single pot process for the preparation of sugar free sustained release liquid suspension comprising;
i. Preparing the wet slurry of drug–resin in a single pot by dispersing Sodium polystyrene sulfonate (Polistirex) resin in purified water and stirring, followed by dispersing in parts the first active ingredient Dextromethorphan Hydrobromide and stirring continuously for a given time interval to obtain the slurry containing Dextromethorphan-Polistirex complex, the unbound Dextromethorphan hydrobromide and unbound resin;
ii. Dispersing in parts the second active ingredient Chlorpheniramine Maleate to the above slurry in said pot with continuous stirring to obtain slurry of Chlorpheniramine–Polistirex complex with the unbound Polistirex and the unbound Chlorpheniramine maleate;
iii. Adding non-crystallized sweetener sorbitol to the above mixture of step ii in said pot and stirring to get the homogenized slurry under close conditions;
iv. Homogenizing the slurry of step iii into a slurry of xanthum gum, methyl hydroxybenzoate, propyl hydroxybenzoate dissolved in polyol followed by addition of pharmaceutically acceptable excipients, non-crystallized sweeteners, optionally pH adjuster in steam jacketed manufacturing vessel and making up to the final volume with purified water to obtain the liquid suspension.

In an aspect, the present process is aqueous based and is free of organic solvent.

In another aspect, the present invention relates to sugar free sustained release liquid suspension comprising uncoated Dextromethorphan Polistirex containing Dextromethorphan HBr and uncoated Chlorpheniramine Polistirex containing Chlorpheniramine maleate prepared by the process of the present invention.

DETAILED DESCRIPTION OF THE INVENTION
The invention will now be described in its optional and preferred embodiments so that various aspects therefore maybe fully understood and appreciated.
In an embodiment, the present invention relates to a cost effective, single pot process for the preparation of sugar free sustained release composition comprising;
i. Preparing the wet slurry of drug–resin in a single pot by dispersing insoluble polymer cation exchange resin in purified water and stirring, followed by dispersing in parts the first active ingredient and stirring continuously for a given time interval to obtain the slurry containing first active-resin complex, unbound first active and unbound resin;
ii. Dispersing in parts the second active ingredient to the above slurry in said pot with continuous stirring until formation of second active –resin complex with the unbound resin in the slurry form and the unbound second active;
iii. Adding non-crystallized sweetener to the above mixture in said pot and stirring to get the homogenized slurry under close conditions;
iv. Homogenizing the slurry of step iii into a slurry of suitable food additives/ viscosifiers and preservatives dissolved in polyol followed by addition of pharmaceutically acceptable excipients, non-crystallized sweeteners, optionally pH adjuster in steam jacketed manufacturing vessel and making up to the final volume with purified water to obtain the composition.

In an embodiment, the percentage of the actives bound to the resin in the slurry is NLT 85%.

In an embodiment, the percentage of the first active ingredient bound to the resin is about 90.50% and the percentage of the second active ingredient bound to the resin is about 87.80%.

The process of the present invention is carried out at a temperature in the range of 25-45°C.

The first active ingredient is selected from Dextromethorphan HBr in an amount of 0.6% w/v to 1.8 % w/v in the in-situ drug resin complex.

The second active ingredient is selected from Chlorpheniramine Maleate in an amount of 0.08%w/v to 0.16% w/v in the in-situ drug resin complex.

The polymer cation exchange resin is preferably selected from Sodium polystyrene sulfonate (Polistirex) in an amount 0.6% w/v-5.4%w/v in the in-situ drug resin complex.

The sweetener is selected from natural high intensity sweetener such as stevia, sorbitol, sucralose, aspartame, saccharin and the like in an amount of 0.001 to 50%w/v. The use of natural high intensity sweetener in the present composition makes it consumer friendly and can be given to patients having high glycemic index with no adverse effects.

The food additive/viscosifier is selected from xanthan gum, arabic gum, guar gum and the like in an amount of 0.001 to 50%w/v, preferably xanthan gum in an amount of 0.5%w/v.

The polyol is selected from propylene glycol in an amount of 1% to 30%w/v .

The pharmaceutically acceptable excipients are selected from carriers, diluents, preservatives, surfactants/ suspending agent emulsifiers, colorants, flavorants, pH adjusters and the like in an amount of 0.001 to 30%w/v.

The surfactant/suspending agent is selected from non-ionic surfactant such as polysorbate 80, poloxamer, polysorbate 20 and the like; colloidal anhydrous silica in an amount of 1-2%w/v. Preferably, the surfactant is polysirbate 80.

The preservatives are selected from Methyl Hydroxybenzoate, Propyl Hydroxybenzoate and the like in an amount of 0.01 to 2%w/v.
The pH adjuster is selected from anhydrous citric acid or its salt.

The composition of the present invention may be formulated as oral composition preferably as liquid suspension form.

In one of the preferred embodiment, the present invention relates to a cost effective, single pot process for the preparation of sugar free Dextromethorphan HBr and Chlorpheniramine Maleate sustained release liquid suspension comprising;
i. Preparing the wet slurry of drug–resin in a single pot by dispersing Sodium polystyrene sulfonate (Polistirex) resin in purified water and stirring, followed by dispersing in parts the first active ingredient Dextromethorphan Hydrobromide and stirring continuously for a given time interval to obtain a slurry containing Dextromethorphan-polistirex complex, unbound Dextromethorphan and unbound polistirex;
ii. Dispersing in parts the second active ingredient Chlorpheniramine Maleate to the above slurry in said pot with continuous stirring to obtain slurry of Chlorpheniramine–polistirex complex with unbound polistirex and the unbound Chlorpheniramine Maleate;
iii. Adding non-crystallized sweetener sorbitol to the above mixture of step ii in said pot and stirring to get the homogenized slurry under close conditions;
iv. Homogenizing the slurry of step iii into a slurry of xanthum gum, methyl hydroxybenzoate, propyl hydroxybenzoate dissolved in polyol followed by addition of pharmaceutically acceptable excipients, non-crystallized sweeteners, optionally pH adjuster in steam jacketed manufacturing vessel and making up to the final volume with purified water to obtain the liquid suspension.

According to the process of the present invention, to the purified water in a stainless steel vessel was dispersed insoluble polymer cation exchange resin selected from sodium polystyrene sulfonate (Polistirex) and stirred to make the slurry. This was followed by addition in parts of the first active ingredient Dextromethorphan Hydrobromide with continuous stirring to obtain the slurry containing Dextromethorphan Polistirex complex and unbound polistirex resin. To the mixture in said vessel was dispersed the second active ingredient Chlorpheniramine Maleate and stirring until formation of slurry of Chlorpheniramine-Polistirex complex with the unbound Polistirex resin, Further, to the mixture in said vessel was added non-crystallized sweetener and stirred constantly to form the homogenous slurry under close condition.

The as prepared slurry of Dextromethorphan-Polistirex complex and Chlorpheniramine-Polistirex complex, the unbound actives were added into steam jacketed manufacturing vessel containing the homogenous slurry of food additives/viscosifiers and preservatives in polyol, followed by addition of suitable pharmaceutically acceptable excipients, non-crystallized sweetener, optionally pH adjuster and stirred to homogenize and made up to the final volume with purified water to obtain the desired product.

The process of the present invention was carried out at a temperature ranging between 25-45°C.

In the process of the present invention, the percentage of Dextromethorphan HBr bound to the resin and the percentage of Chlorpheniramine Maleate bound to the resin is NLT 85%.

In the present process, the resultant slurry of drug-resin complex was incorporated directly in to the liquid vehicle to obtain the suspension.

The process of the present invention was carried out in aqueous medium.

The sweetener is selected from natural high intensity sweetener such as stevia, sorbitol, sucralose, aspartame, saccharin and the like; preferably sorbitol in an amount of 0.001 to 50%w/v. The use of natural high intensity sweetener in the present composition makes it consumer friendly and can be given to patients having high glycemic index with no adverse effects.

The food additive/ viscosifier is selected from xanthan gum, arabic gum, guar gum and the like; preferably xanthan gum in an amount of 0.001 to 50%w/v, preferably xanthan gum in an amount of 0.5%w/v.

The polyol is selected from polyethylene glycol in an amount of 1% to 30%w/v.

The pharmaceutically acceptable excipients are selected from carriers, diluents, preservatives, surfactants/suspending agents, emulsifiers, colorants, flavorants, pH adjusters and the like in an amount of 0.001 to 30%w/v.

The preservatives are selected from Methyl Hydroxybenzoate, Propyl Hydroxybenzoate and the like in an amount of 0.01 to 2%w/v.

The pH adjuster is selected from anhydrous citric acid or its salt.

The surfactant/suspending agent is selected from non-ionic surfactant such as polysorbate 80, poloxamer, polysorbate 20 and the like; colloidal anhydrous silica in an amount of 1-2%w/v. Preferably, the surfactant is polysirbate 80.

The final liquid suspension is free of natural sugar, any coating material and is free of lumps and therefore the need to store the liquid suspension at lower temperature is not required.

In an aspect, the process of the present invention can be scaled up to industrial level.
The process of the present invention is simple since the process is carried in a single pot to prepare the slurry of drug-resin complex and adding the resultant slurry directly in to the liquid vehicle to make the suspension. There is no coating of the drug-resin complex hence ameliorates the step of coating, there is less use of equipment in the manufacturing process making it industrially feasible.

In an embodiment, the present invention relates to sugar free, uncoated Dextromethorphan Polistirex containing Dextromethorphan HBr and uncoated Chlorpheniramine Polistirex containing Chlorpheniramine maleate for sustained release composition.

In another embodiment, the present invention relates to sugar free sustained release liquid composition comprising uncoated Dextromethorphan Polistirex containing Dextromethorphan HBr and uncoated Chlorpheniramine Polistirex containing Chlorpheniramine maleate prepared by the process of the present invention together with one or more pharmaceutically acceptable excipients.

The sugar free sustained release liquid composition is in the form of liquid suspension.

In an embodiment, the sugar free sustained release liquid suspension has a pH ranging between 3.0 to 4.0 and viscosity ranging between 5 to 500cps.

In another embodiment, the sugar free sustained release liquid suspension comprising uncoated Dextromethorphan Polistirex containing Dextromethorphan HBr and uncoated Chlorpheniramine Polistirex containing Chlorpheniramine maleate prepared by the process of the present invention together with one or more pharmaceutically acceptable excipients is used to alleviate the symptoms of cough associated with acute upper respiratory tract infection in a patient in need thereof.

The sustained release composition of the present invention is formulated for oral administration as liquid suspension.

In another embodiment, the composition of the present invention provides in vitro sustained release of Dextromethorphan HBr and Chlorpheniramine Maleate, wherein, the release rate of the actives is NLT 70.0% after 12 hours, preventing dose dumping. The formulation obtained by the process of the present invention provides sustained release thus reducing the frequency of dosages and is therefore patient friendly.

Examples:

Example 1: General Preparation of Dextromethorphan HBr & Chlorpheniramine Maleate Sustained Release liquid Suspension

Composition:
Ingredients Amount in 100ml
Dextromethorphan Hydrobromide 0.6% w/v-1.8%w/v
Sodium Polystyrene Sulphonate 0.6% w/v-5.4%w/v
Chlorpheniramine Maleate 0.04% -0.16%w/v
Xanthan Gum 0.001 to 50%w/v
Propylene Glycol 1% to 30%w/v
Liquid Sorbitol (Non-Crystallising) 0.001 to 50%w/v
Methyl Hydroxy Benzoate (Methylparaben) 0.01 to 2%w/v
Propyl Hydroxybenzoate (Propylparaben) 0.01 to 2%w/v
Tween 80 (Polysorbate-80) 1-2%w/v
Colour Ponceu 4R Supra 0.001 to 30%w/v
Essence Black Currant / Cherry 0.001 to 30%w/v.
Sucralose Colloidal Anhydrous Silica
Colloidal Anhydrous Silica Colloidal Anhydrous Silica
Anhydrous Citric Acid q.s
Purified Water q.s

Manufacturing Process:
To the purified water in stainless steel vessel was dispersed sodium polystyrene sulfonate (insoluble polymer cation exchange resin-Polistirex). Stirred the mixture for 20–30 minutes to make the slurry. Dispersed part of Dextromethorphan Hydrobromide IP of the total amount to the slurry with continuous gentle stir for 2 - 3 hours to make complex of Dextromethorphan Hydrobromide IP with Sodium polystyrene sulfonate and added remaining part of Dextromethorphan Hydrobromide IP in said slurry and mixed for 5 - 15 minutes to obtain slurry containing Dextromethorphan-Polistirex complex; the unbound Dextromethorphan Hydrobromide and unbound polistirex.
Dispersed in part Chlorpheniramine Maleate IP of the total amount with continuous gentle stirring for 15 - 30 minutes to the above slurry followed by adding the remaining part of Chlorpheniramine Maleate IP to the slurry and mixed for 5 – 15 minutes to obtain Chlorpheniramine-polistriex complex formed with the unbound polistirex and unbound Chlorpheniramine Maleate.
Note: Checked the state of the mixture so as to be free from lumps.
The percentage of Dextromethorphan HBr bound to the resin is about 90.50% and the percentage of Chlorpheniramine Maleate bound to the resin is about 87.80%.
Added Liquid Sorbitol (Non-Crystallising) was added into above slurry in the vessel and mixed for 10 – 30 minutes to get homogenous slurry under close condition.
Note: Checked the state of the mixture so as to be free from lumps.
Prepared the slurry of Xanthan gum in Propylene glycol, dissolved Methyl Hydroxybenzoate, Propyl Hydroxybenzoate to that with gentle heating in steam jacketed Manufacturing Vessel with stirring and allowed soaking for 30mins – 1.5 hour.
Note: Checked the state of the mixture so as to be free from lumps.
Added the slurry of uncoated Dextromethorphan Polistirex complex, uncoated Chlorpheniramine Polistirex complex and liquid sorbitol to the above mixture in the jacketed manufacturing vessel with stirring to get homogenous mixture followed by addition of polysorbate 80 in said manufacturing vessel and stirred for 5 -30 minutes to get uniform mixing.
Note: Checked the state of the mixture so as to be free from lumps and gritty particles.
Added to the manufacturing vessel solution of sucralose in purified water and stirred for 5 -30 minutes.
Note: Checked the state of the mixture so as to be free from lumps and is an uniform mixture.
Added to the manufacturing vessel dispersed Colloidal Anhydrous Silica (Aerosil) in purified water and stirred.
Note: Checked the state of the mixture so as to be free from lumps and is an uniform mixture.
Added to the manufacturing vessel colorant Ponceau 4R Supra in purified water and stirred.
Note: Checked the state of the mixture so as to be free from lumps and is an uniform mixture.
Added to the manufacturing vessel the Essence Cherry / Black Currant and stirred for 5 - 30 minutes.
Made the volume up to 90% with Purified Water and checked the pH 3.0 – 6.0 of the suspension. If required, pH is adjusted with Citric acid solution or sodium citrate solution.
Note: Checked the state of the mixture to be free from lumps and uniform mixture.
Step 10: Made up the final volume with purified water. Stirred the bulk in manufacturing vessel for about 30 min – 1.5 hr.
Yield: 99.5% - 100%.
Step 11: Bottle Filling:

Example 2: Composition
Ingredients Amount in 5ml
Dextromethorphan Hydrobromide 45 mg
Sodium Polystyrene Sulphonate 67.5 mg
Chlorpheniramine Maleate 2 mg
Xanthan Gum 20 mg
Propylene Glycol 120 mg
Liquid Sorbitol (Non-Crystallising) 5 mg
Methyl Hydroxy Benzoate (Methylparaben) 10 mg
Propyl Hydroxybenzoate (Propylparaben) 1 mg
Tween 80 (Polysorbate-80) 6 mg
Colour Ponceu 4R Supra 0.6 mg
Essence Black Currant / Cherry 25 mg
Sucralose 8 mg
Colloidal Anhydrous Silica 35 mg
Anhydrous Citric Acid q.s
Purified Water q.s

Process: The liquid suspension was prepared by the process of example 1.

Example 3: Composition

Ingredients Amount in 5 ml
Dextromethorphan Hydrobromide 30mg
Sodium Polystyrene Sulphonate 60mg
Chlorpheniramine Maleate 4mg
Xanthan Gum 20 mg
Propylene Glycol 120 mg
Liquid Sorbitol (Non-Crystallising) 5 mg
Methyl Hydroxy Benzoate (Methylparaben) 10 mg
Propyl Hydroxybenzoate (Propylparaben) 1 mg
Tween 80 (Polysorbate-80) 6 mg
Colour Ponceu 4R Supra 0.6 mg
Essence Black Currant / Cherry 25 mg
Sucralose 8 mg
Colloidal Anhydrous Silica 35 mg
Anhydrous Citric Acid q.s
Purified Water q.s

Process: The liquid suspension was prepared by the process of example 1.

Example 4: Composition

Ingredients Amount in 5ml
Dextromethorphan Hydrobromide 45mg
Sodium Polystyrene Sulphonate 60mg
Chlorpheniramine Maleate 8mg
Xanthan Gum 20 mg
Propylene Glycol 120 mg
Liquid Sorbitol (Non-Crystallising) 5 mg
Methyl Hydroxy Benzoate (Methylparaben) 10 mg
Propyl Hydroxybenzoate (Propylparaben) 1 mg
Tween 80 (Polysorbate-80) 6 mg
Colour Ponceu 4R Supra 0.6 mg
Essence Black Currant / Cherry 25 mg
Sucralose 8 mg
Colloidal Anhydrous Silica 35 mg
Anhydrous Citric Acid q.s
Purified Water q.s

Process: The liquid suspension was prepared by the process of example 1.

Example 5: Dissolution Profile
Table 1:

Dextromethorphan Hydrobromide
After 30 minutes Between 25.0 - 45.0 %.

After 3 hours Between 45.0 - 65.0 %
After 12 hours NLT 70.0 %.
Chlorpheniramine Maleate
After 30 minutes NMT 10%
After 3 hours Between 30 - 60.0 %
After 12 hours NLT 70.0 %

Example 6: Stability data at 30oC(±2)/75%RH (±5) and at 40oC (±2)/75%RH (±5) of the composition illustrated in example 3 prepared by the present product

Table 2:

Dextromethorphan Hydrobromide and Chlorpheniramine Maleate Sustained Release Oral Suspension as per example 3
Batch No: T0001 Batch size: 5. Liter
Mfg. Date: JAN.2022 Date of Charging: 12.01.2022
Packing: 100 ml in PET Bottle. Storage condition: 30°C ± 2 °C, 75 % ± 5 %

Sr. No. Test Parameter Specification Initial Duration in Months with Date of Analysis
12th Month 18th Month 24th Month
1. Description Reddish coloured suspension free from any foreign particles filled in amber color pet bottle.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution. Complies Complies
2. Identification (By HPLC)

A. For Dextromethorphan Hydrobromide

B. For Chlorpheniramine maleate

C. For Methylparaben IP

D. For Propylparaben IP In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution. Complies

Complies

Complies

Complies Complies

Complies

Complies

Complies
3. pH 3.0 to 5.0 3.456 3.741
4. Weight/ml Between 0.90 gm to 1.10 g/ml 1.04 g/ml 1.043
5. Dissolution (By HPLC)
A. For Dextromethorphan Hydrobromide:
After 30 minutes
After 3 hours
After 12 hours
-Between 25.0 % and 45.0 % of the labeled amount.
-Between 45.0 % and 65.0 % of the labeled amount.
-Not less than 70.0 % of the labeled amount. Min. Max. Avg. Min Max. Avg. Min Max. Avg. Min Max. Avg.
35.32 % 39.35 % 36.92 % 27.95 38.84 32.88
51.73 % 55.34 % 53.45 % 49.05 56.29 52.80
85.36 % 89.84 % 87.71 % 82.82 94.61 91.21
B. For Chlorpheniramine maleate

After 30 minutes in 0.1 N HCl
After 3 hours in pH 4.5
After 12 hours in buffer pH 6.8 -Not more than 10.0 % of the Labeled amount.
-Between 30.0 % and 60.0 % of the labeled amount.
-Not less than 70.0 % of the Labeled amount. 1.58 % 2.66 % 2.13 % 1.16 1.97 1.59
44.71 % 49.38 % 47.12 % 50.55 53.66 53.66
95.42 % 99.12 % 97.06 % 82.97 95.08 91.12
6. Assay:
Dextromethorphan Polistirex Eq. to Dextromethorphan Hydrobromide IP 30 mg
Chlorpheniramine Polistirex Eq. to Chlorpheniramine Maleate IP 4 mg.

Methylparaben IP 10 mg

Propylparaben IP 1 mg
(90.0 -110.0 % of label claim)

(90.0 -110.0 % of label claim)

(NMT 120.0 % of label claim)
(NMT 120% of label claim) In mg In % In mg In % In mg In % In mg In %
30.25 100.83 30.16 100.53
3.9728 99.32 3.93 98.27
9.889 98.89 9.80 97.96
0.9869 98.69 0.9787 97.87
7. Related Substances
7.A Chlorpheniramine maleate Single Maximum Impurity: 0.5%
Total Impurity: 1.0% 0.064%
0.094%
7.B Dextromethorphan Hydrobromide
Impurity A NMT 0.2% ND*
Impurity B NMT 0.2% ND
Impurity C NMT 0.2% 0.098%
Impurity D NMT 0.2% ND*
Unspecified impurities NMT 0.2% ND
Total Impurity NMT 1.0% 0.098%
8. *Microbiological purity:
Total viable bacterial count
Total fungal count
Escherichia coli Not more than 100 cfu per ml.
Not more than 10 cfu per ml.
Absent per ml
10 cfu/g
<10 cfu/g
Absent/g NA
9. Date of Withdraw NA NA 12.01.2023
10. Date of Analysis NA 10.01.2022 21.01.2023

*ND: Not Detected

Conclusion: The Product is within the specification at 30°C / 75% RH for 12Months, &/ No significant change is observed during this period.

Table 3:
Dextromethorphan Hydrobromide and Chlorpheniramine Maleate Sustained Release Oral Suspension as per example 3
Batch No: T0001 Batch size: 5. Liter
Mfg. Date: JAN.2022 Date of Charging 12.01.2022
Packing: 100 ml in PET Bottle. Storage condition: 40°C ± 2 °C, 75 % ± 5 %

Sr. No. Test Parameter Specification Initial Duration in Months with Date of Analysis
3rd Month 6th Month
Description Reddish coloured suspension free from any foreign particles filled in amber color pet bottle.

In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.

In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
Complies Complies Complies
2. Identification (By HPLC)

E. For Dextromethorphan Hydrobromide

F. For Chlorpheniramine maleate

G. For Methylparaben IP

H. For Propylparaben IP In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution. Complies

Complies

Complies

Complies Complies

Complies

Complies

Complies Complies

Complies

Complies

Complies
3. pH 3.0 to 5.0 3.456 3.553 3.628
4. Weight/ml Between 0.90 gm to 1.10 g/ml 1.04 g/ml 1.042 g/ml 1.042 g/ml
5. Dissolution (By HPLC)
C. For Dextromethorphan Hydrobromide:
After 30 minutes
After 3 hours
After 12 hours
-Between 25.0 % and 45.0 % of the labeled amount.
-Between 45.0 % and 65.0 % of the labeled amount.
-Not less than 70.0 % of the labeled amount. Mini. Maxi. Avg. Mini. Maxi. Avg. Mini. Maxi. Avg.

35.32 % 39.35 % 36.92 % 30.66 % 40.11 % 38.55 % 30.56 % 41.43 % 38.15 %
51.73 % 55.34 % 53.45 % 50.15 % 62.22 % 57.56 % 48.65 % 62.48 % 58.66 %
85.36 % 89.84 % 87.71 % 86.20 % 88.44 % 87.54 % 84.66 % 87.22 % 86.12 %
D. For Chlorpheniramine maleate

After 30 minutes in 0.1 N HCl
After 3 hours in pH 4.5
After 12 hours in buffer pH 6.8 -Not more than 10.0 % of the Labeled amount.
-Between 30.0 % and 60.0 % of the labeled amount.
-Not less than 70.0 % of the Labeled amount. 1.58 % 2.66 % 2.13 % 1.63 % 2.06 % 1.89 % 1.39 % 1.97 % 1.65 %
44.71 % 49.38 % 47.12 % 50.02 % 57.23 % 54.88 % 51.33 % 58.02 % 54.66 %
95.42 % 99.12 % 97.06 % 85.15 % 98.76 % 97.32 % 82.22 % 99.12 % 96.05 %
6. Assay:
Dextromethorphan Polistirex Eq. to Dextromethorphan Hydrobromide IP 30 mg
Chlorpheniramine Polistirex Eq. to Chlorpheniramine Maleate IP 4 mg.
Methylparaben IP 10 mg.
Propylparaben IP 1 mg. (90.0 -110.0 % of label claim)

(90.0 -110.0 % of label claim)
(NMT 120.0 % of label claim)
(NMT 120% of label claim) In mg In % In mg In % In mg In %
30.25 100.83 30.14 100.47 30.01 100.03
3.9728 99.32 3.93 98.25 3.91 97.75
9.889 98.89 9.84 98.40 9.81 98.10
0.9869 98.69 0.9847 98.47 0.9811 98.11
7. *Microbiological purity:
Total viable bacterial count
Total fungal count
Escherichia coli Not more than 100 cfu per ml.
Not more than 10 cfu per ml.
Absent per ml
10 cfu/g
<10 cfu/g
Absent/g NA 30 cfu/g
<10 cfu/g
Absent/g
8. Date of Withdraw NA NA 12.04.2022 12.07.2022
9. Date of Analysis NA 10.01.2022 22.04.2022 21.07.2022

Conclusion: The Product is within the specification at 40°C / 75% RH for 12 Months, & No significant change is observed during this period.

Table 4:

Dextromethorphan Hydrobromide and Chlorpheniramine Maleate Sustained Release Oral Suspension as per example 3
Batch No: T0002 Batch size: 5 Liter
Mfg. Date: JAN.2022 Date of Charging: 12.01.2022
Packing: 100 ml in PET Bottle. Storage condition: 30°C ± 2 °C, 75 % ± 5 %

Sr. No. Test Parameter Specification Initial Duration in Months with Date of Analysis
12th Month 18th Month 24th Month
1. Description Reddish coloured suspension free from any foreign particles filled in amber color pet bottle. Complies Complies
2. Identification (By HPLC)

I. For Dextromethorphan Hydrobromide

J. For Chlorpheniramine maleate

K. For Methylparaben IP

L. For Propylparaben IP In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution. Complies

Complies

Complies

Complies Complies

Complies

Complies

Complies
3. pH 3.0 to 5.0 3.476 3.681
4. Weight/ml Between 0.90 gm to 1.10 g/ml 1.02 g/ml 1.025 g/ml
5. Dissolution (By HPLC)
E. For Dextromethorphan Hydrobromide:
After 30 minutes
After 3 hours
After 12 hours -Between 25.0 % and 45.0 % of the labeled amount.
-Between 45.0 % and 65.0 % of the labeled amount.
-Not less than 70.0 % of the labeled amount. Min. Max. Avg. Min. Max. Avg. Min. Max. Avg. Min. Max. Avg.
34.32 % 37.45 % 35.94 % 26.93 34.59 31.30
50.47 % 53.81 % 52.28 % 49.03 57.75 54.63
83.46 % 88.35 % 86.03 % 86.62 95.01 92.05
F. For Chlorpheniramine maleate

After 30 minutes in 0.1 N HCl
After 3 hours in pH 4.5
After 12 hours in buffer pH 6.8 Not more than 10.0 % of the Labeled amount.
Between 30.0 % and 60.0 % of the labeled amount.
Not less than 70.0 % of the Labeled amount. 1.60 % 2.60 % 2.13 % 1.21 1.42 1.30
44.97 % 49.55 % 46.61 % 50.04 55.34 52.90
92.83% 96.37 % 94.75 % 84.69 94.83 91.21
6. Assay:
Dextromethorphan Polistirex Eq. to Dextromethorphan Hydrobromide IP 30 mg
Chlorpheniramine Polistirex Eq. to Chlorpheniramine Maleate IP 4 mg
Methylparaben IP 10 mg

Propylparaben IP 1 mg (90.0 -110.0 % of label claim)

(90.0 -110.0 % of label claim)

(NMT 120.0 % of label claim)

(NMT 120% of label claim) In mg In % In mg In % In mg In % In mg In %
29.43 98.12 29.75 99.18
3.9276 98.19 3.92 98.07
10.007 100.07 9.703 97.03
0.9771 97.71 0.9684 96.84
7. Related Substances
7.A Chlorpheniramine maleate Single Maximum Impurity: 0.5%
Total Impurity: 1.0% 0.071%
0.101%
7.B Dextromethorphan Hydrobromide
Impurity A NMT 0.2% ND*
Impurity B NMT 0.2% ND
Impurity C NMT 0.2% 0.097%
Impurity D NMT 0.2% ND*
Unspecified impurities NMT 0.2% ND
Total Impurity NMT 1.0% 0.097%
8. *Microbiological purity:
Total viable bacterial count
Total fungal count
Escherichia coli Not more than 100 cfu per ml.
Not more than 10 cfu per ml.
Absent per ml
10 cfu/g
<10 cfu/g
Absent/g NA NA NA
9. Date of Withdraw NA NA 12.01.2023
10. Date of Analysis NA 11.01.2022 21.01.2023

*ND: Not Detected

Conclusion: The Product is within the specification at 30°C / 75% RH for 12Months, &/ No significant change is observed during this period.

Table 5:

Dextromethorphan Hydrobromide and Chlorpheniramine Maleate Sustained Release Oral Suspension as per example 3
Batch No: T0002 Batch size: 5 Liter
Mfg. Date: JAN.2022 Storage condition: 40°C ± 2 °C, 75 % ± 5 %
Packing: 100 ml in PET Bottle. Date of Charging: 12.01.2022

Sr. No. Test Parameter Specification Initial Duration in Months with Date of Analysis
3rd Month 6th Month
1. Description Reddish coloured suspension free from any foreign particles filled in amber color pet bottle.

In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution. Complies

Complies

Complies

Complies

Complies

Complies

2. Identification (By HPLC)

M. For Dextromethorphan Hydrobromide

N. For Chlorpheniramine maleate

O. For Methylparaben IP

P. For Propylparaben IP In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution. Complies

Complies

Complies

Complies

Complies

Complies

Complies

Complies

Complies

3. pH 3.0 to 5.0 3.476 3.528 3.633
4. Weight/ml Between 0.90 gm to 1.10 g/ml 1.02 g/ml 1.022 g/ml 1.022 g/ml
5. Dissolution (By HPLC)
G. For Dextromethorphan Hydrobromide:
After 30 minutes
After 3 hours
After 12 hours
-Between 25.0 % and 45.0 % of the labeled amount.
-Between 45.0 % and 65.0 % of the labeled amount.
-Not less than 70.0 % of the labeled amount. Mini. Maxi. Avg. Mini. Maxi. Avg. Mini. Maxi. Avg.

34.32 % 37.45 % 35.94 % 26.85 % 42.61 % 33.62 % 30.33 % 40.61 % 35.60 %
50.47 % 53.81 % 52.28 % 51.55 % 60.60 % 55.67 % 51.55 % 60.10 % 55.67 %
83.46 % 88.35 % 86.03 % 82.88 % 86.56 % 85.50 % 82.08 % 87.26 % 85.12 %
H. For Chlorpheniramine maleate

After 30 minutes in 0.1 N HCl
After 3 hours in pH 4.5
After 12 hours in buffer pH 6.8 Not more than 10.0 % of the Labeled amount.
Between 30.0 % and 60.0 % of the labeled amount.
Not less than 70.0 % of the Labeled amount. 1.60 % 2.60 % 2.13 % 1.05 % 2.12 % 1.85 % 1.00 % 1.74 % 1.67 %
44.97 % 49.55 % 46.61 % 50.65 % 58.32 % 55.20 % 50.05 % 57.30 % 56.23 %
92.83% 96.37 % 94.75 % 85.29 % 96.46 % 92.22 % 87.20 % 95.11 % 92.02 %
6. Assay:
Dextromethorphan Polistirex Eq. to Dextromethorphan Hydrobromide IP 30 mg
Chlorpheniramine Polistirex Eq. to Chlorpheniramine Maleate IP 4 mg
Methylparaben IP 10 mg

Propylparaben IP 1 mg (90.0 -110.0 % of label claim)

(90.0 -110.0 % of label claim)

(NMT 120.0 % of label claim)
(NMT 120% of label claim) In mg In % In mg In % In mg In %
29.4360 98.12 29.55 98.50 29.35 97.83
3.9276 98.19 3.91 97.75 3.85 96.25
10.0070 100.07 9.91 99.10 9.87 98.70
0.9771 97.71 0.9710 97.10 0.9672 96.72
7. *Microbiological purity:
Total viable bacterial count
Total fungal count
Escherichia coli Not more than 100 cfu per ml.
Not more than 10 cfu per ml.
Absent per ml
10 cfu/g
<10 cfu/g
Absent/g NA 30 cfu/g
<10 cfu/g
Absent/g
8. Date of Withdraw NA NA 12.04.2022 12.07.2022
9. Date of Analysis NA 11.01.2022 22.04.2022 21.07.2022

Conclusion: The Product is within the specification at 40°C / 75% RH for 12Months, & No significant change is observed during this period.

Table 6:

Dextromethorphan Hydrobromide and Chlorpheniramine Maleate Sustained Release Oral Suspension as per example 3
Batch No: T0003 Batch size: 5 Liter
Mfg. Date: JAN.2022 Date of Charging 12.01.2022
Packing: 100 ml in PET Bottle. Storage condition: 30°C ± 2 °C, 75 % ± 5 %

Sr. No. Test Parameter Specification Initial Duration in Months with Date of Analysis
12th Month 18th Month 24th Month
1. Description Reddish coloured suspension free from any foreign particles filled in amber color pet bottle. Complies Complies
2. Identification (By HPLC)

Q. For Dextromethorphan Hydrobromide

R. For Chlorpheniramine maleate

S. For Methylparaben IP

T. For Propylparaben IP In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution. Complies

Complies

Complies

Complies Complies

Complies

Complies

Complies
3. pH 3.0 to 5.0 3.489 3.662
4. Weight/ml Between 0.90 gm to 1.10 g/ml 1.01 g/ml 1.014
5. Dissolution (By HPLC)
I. For Dextromethorphan Hydrobromide:
After 30 minutes
After 3 hours
After 12 hours
-Between 25.0 % and 45.0 % of the labeled amount.
-Between 45.0 % and 65.0 % of the labeled amount.
-Not less than 70.0 % of the labeled amount. Mini. Maxi. Avg. Min. Max. Avg. Min. Max. Avg. Min. Max. Avg.
35.43 % 36.81 % 35.92 % 28.79 34.20 31.89
52.66 % 55.75 % 54.25 % 47.22 56.31 53.00
88.49 % 92.46 % 90.17 % 84.01 95.03 91.11
J. For Chlorpheniramine maleate

After 30 minutes in 0.1 N HCl
After 3 hours in pH 4.5
After 12 hours in pH 6.8 Not more than 10.0 % of the Labeled amount.
Between 30.0 % and 60.0 % of the labeled amount.
Not less than 70.0 % of the Labeled amount. 1.42 % 2.57 % 2.05 % 0.98 1.23 1.13
45.23 % 51.49 % 47.61 % 48.81 54.87 52.19
87.21 % 94.21 % 90.87 % 83.92 95.86 92.02
6. Assay:
Dextromethorphan Polistirex Eq. to Dextromethorphan Hydrobromide IP 30 mg
Chlorpheniramine Polistirex Eq. to Chlorpheniramine Maleate IP 4 mg
Methylparaben IP 10 mg

Propylparaben IP 1 mg (90.0 -110.0 % of label claim)

(90.0 -110.0 % of label claim)

(NMT 120.0 % of label claim)
(NMT 120% of label claim) In mg In % In mg In % In mg In % In mg In %
30.69 102.30 29.94 99.81
3.9652 99.13 3.93 98.15
9.7540 97.54 9.81 98.13
0.9698 96.98 0.9711 97.11
7. Related Substances
7.A Chlorpheniramine maleate Single Maximum Impurity: 0.5%
Total Impurity: 1.0% 0.064%
0.094%
7.B Dextromethorphan Hydrobromide
Impurity A NMT 0.2% ND*
Impurity B NMT 0.2% ND
Impurity C NMT 0.2% 0.098%
Impurity D NMT 0.2% ND*
Unspecified impurities NMT 0.2% ND
Total Impurity NMT 1.0% 0.098%
7. *Microbiological purity:
Total viable bacterial count
Total fungal count
Escherichia coli Not more than 100 cfu per ml.
Not more than 10 cfu per ml.
Absent per ml
20 cfu/g
<10 cfu/g
Absent/g NA NA NA
8. Date of Withdraw NA NA 12.01.2023
9. Date of Analysis NA 12.01.2022 21.01.2023

*ND: Not Detected
Conclusion: The Product is within the specification at 30°C / 75% RH for 12Months, No significant change is observed during this period.

Table 7:
Dextromethorphan Hydrobromide and Chlorpheniramine Maleate Sustained Release Oral Suspension as per example 3
Batch No: T0003 Batch size: 5 Liter
Mfg. Date: JAN.2022 Date of Charging: 12.01.2022
Packing: 100 ml in PET Bottle. Storage condition: 40°C ± 2 °C, 75 % ± 5 %

Sr. No. Test Parameter Specification Initial Duration in Months with Date of Analysis
3rd Month 6th Month
1. Description Reddish coloured suspension free from any foreign particles filled in amber color pet bottle.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution. Complies Complies Complies
2. Identification (By HPLC)

U. For Dextromethorphan Hydrobromide

V. For Chlorpheniramine maleate

W. For Methylparaben IP

X. For Propylparaben IP In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution. Complies

Complies

Complies

Complies Complies

Complies

Complies

Complies Complies

Complies

Complies

Complies
3. pH 3.0 to 5.0 3.489 3.558 3.633
4. Weight/ml Between 0.90 gm to 1.10 g/ml 1.01 g/ml 1.013 g/ml 1.012 g/ml
5. Dissolution (By HPLC)
K. For Dextromethorphan Hydrobromide:
After 30 minutes
After 3 hours
After 12 hours
-Between 25.0 % and 45.0 % of the labeled amount.
-Between 45.0 % and 65.0 % of the labeled amount.
-Not less than 70.0 % of the labeled amount. Mini. Maxi. Avg. Mini. Maxi. Avg. Mini. Maxi. Avg.
35.43 % 36.81 % 35.92 % 31.55 % 40.61 % 35.60 % 30.50 % 41.11 % 36.30 %
52.66 % 55.75 % 54.25 % 51.55 % 60.60 % 55.67 % 50.55 % 61.62 % 56.87 %
88.49 % 92.46 % 90.17 % 87.88 % 91.56 % 90.50 % 87.38 % 89.56 % 88.22 %
L. For Chlorpheniramine maleate

After 30 minutes in 0.1 N HCl
After 3 hours in pH 4.5
After 12 hours in pH 6.8 Not more than 10.0 % of the Labeled amount.
Between 30.0 % and 60.0 % of the labeled amount.
Not less than 70.0 % of the Labeled amount. 1.42 % 2.57 % 2.05 % 0.89 % 1.88 % 1.54 % 0.95 % 1.76 % 1.37 %
45.23 % 51.49 % 47.61 % 52.15 % 56.30 % 54.67 % 51.55 % 54.44 % 53.22 %
87.21 % 94.21 % 90.87 % 84.28 % 93.56 % 89.50 % 85.88 % 91.06 % 88.50 %
6. Assay:
Dextromethorphan Polistirex Eq. to Dextromethorphan Hydrobromide IP 30 mg
Chlorpheniramine Polistirex Eq. to Chlorpheniramine Maleate IP 4 mg
Methylparaben IP 10 mg

Propylparaben IP 1 mg (90.0 -110.0 % of label claim)

(90.0 -110.0 % of label claim)

(NMT 120.0 % of label claim)
(NMT 120% of label claim) In mg In % In mg In % In mg In %
30.69 102.30 30.45 101.5 30.12 100.4
3.9652 99.13 3.94 98.50 3.89 97.25
9.7540 97.54 9.82 98.20 9.72 97.20
0.9698 96.98 0.9770 97.70 0.9670 96.70
7. *Microbiological purity:
Total viable bacterial count
Total fungal count
Escherichia coli Not more than 100 cfu per ml.
Not more than 10 cfu per ml.
Absent per ml
20 cfu/g
<10 cfu/g
Absent/g NA 10 cfu/g
<10 cfu/g
Absent/g
8. Date of Withdraw NA NA 12.04.2022 12.07.2022
9. Date of Analysis NA 12.01.2022 22.04.2022 21.07.2022

Conclusion: The Product is within the specification at 40°C / 75% RH for 12 Months, No significant change is observed during this period.

Although the invention has been described in detail in the foregoing for the purpose of illustration, it is to be understood that such detail is solely for that purpose and that variations can be made therein by those skilled in the art without departing from the spirit and scope of the invention except as it may be limited by the claims.
,CLAIMS:1. A cost effective, single pot process for the preparation of sugar free sustained release composition comprising;
i. Preparing the wet slurry of drug–resin complexes in a single pot by dispersing insoluble polymer cation exchange resin in purified water and stirring, followed by dispersing in parts the first active ingredient and stirring continuously for a given time interval to obtain the slurry containing first active-resin complex; the unbound first active and unbound resin;
ii. Dispersing in parts the second active ingredient to the above slurry in said pot with continuous stirring until formation of second active –resin complex with the unbound resin in the slurry form and the unbound second active;
iii. Adding non-crystallized sweetener to the above mixture in said pot and stirring to get the homogenized slurry under close conditions;
iv. Homogenizing the slurry of step iii in a slurry of suitable food additives/ viscosifiers and preservatives dissolved in polyol followed by addition of pharmaceutically acceptable excipients, non-crystallized sweeteners, optionally pH adjuster in steam jacketed manufacturing vessel and making up to the final volume with purified water to obtain the composition.

2. The process as claimed in claim 1, wherein the process is carried out at a temperature in the range of 25°C to 45°C.

3. The process as claimed in claim 1, wherein the first active ingredient is selected from Dextromethorphan HBr in an amount of 0.6% w/v-1.8%w/v.

4. The process as claimed in claim 1, wherein the second active ingredient is selected from Chlorpheniramine Maleate in an amount of 0.04% -0.16%w/w/v.

5. The process as claimed in claim 1, wherein the polymer cation exchange resin is selected from Sodium polystyrene sulfonate (Polistirex) in an amount of 0.6% w/v-5.4%w/w/v.

6. The process as claimed in claim 1, wherein the process is carried out in aqueous medium.

7. The process as claimed in claim 1, wherein the sustained release composition is in the form of oral liquid suspension.

8. A cost effective, single pot process for the preparation of sugar free Dextromethorphan HBr and Chlorpheniramine maleate sustained release composition comprising;
i. Preparing the wet slurry of drug–resin complex in a single pot by dispersing Sodium polystyrene sulfonate (Polistirex) resin in purified water and stirring, followed by dispersing in parts the first active ingredient Dextromethorphan Hydrobromide and stirring continuously for a given time interval to obtain a slurry containing Dextromethorphan-polistirex complex, the unbound Dextromethorphan Hydrobromide and unbound polistirex;
ii. Dispersing in parts the second active ingredient Chlorpheniramine Maleate to the above slurry in said pot with continuous stirring to obtain slurry of Chlorpheniramine complex with unbound polistirex and the unbound Chlorpheniramine maleate;
iii. Adding non-crystallized sweetener sorbitol to the above mixture of step ii in said pot and stirring to get the homogenized slurry under close conditions;
iv. Homogenizing the slurry of step iii in a slurry of xanthum gum, methyl hydroxybenzoate, propyl hydroxybenzoate dissolved in polyol followed by addition of pharmaceutically acceptable excipients, non-crystallized sweeteners, optionally pH adjuster in steam jacketed manufacturing vessel and making up to the final volume with purified water to obtain the liquid suspension.

9. The process as claimed in claim 8, wherein the process is carried out in aqueous medium.

10. The process as claimed in claim 1 and 8, wherein the sweetener is selected from the group consisting of stevia, sorbitol, sucralose, aspartame, saccharin and the like in an amount of 0.001 to 50%w/v.

11. The process as claimed in claim 10, wherein the sweetener is sorbitol.

12. The process as claimed in claim 1 and 8, wherein the food additive/viscosifier is selected from xanthan gum, arabic gum, guar gum and the like in an amount of 0.001 to 50%w/v.

13. The process as claimed in claim 12, wherein the food additive is xanthum gum.

14. The process as claimed in claim 1 and 8, wherein the polyol is polyethylene glycol in an amount of 1% to 30%w/v.

15. The process as claimed in claim 1 and 8, wherein the pharmaceutically acceptable excipients are selected from carriers, diluents, preservatives, surfactants/suspending agents, emulsifiers, colorants, flavorants, pH adjusters and the like in an amount of 0.001 to 30%w/v.

16. The process as claimed in claim 15, wherein the preservatives are selected from Methyl Hydroxybenzoate, Propyl Hydroxybenzoate and the like in an amount of 0.01 to 2%w/v; the surfactants/suspending agent is polysorbate 80 in an amount of 1-2%w/v.

17. A sugar free, uncoated Dextromethorphan Polistirex containing Dextromethorphan HBr and uncoated Chlorpheniramine Polistirex containing Chlorpheniramine maleate for sustained release composition.

18. A sugar free sustained release composition comprising uncoated Dextromethorphan Polistirex containing Dextromethorphan HBr and uncoated Chlorpheniramine Polistirex conatining Chlorpheniramine maleate prepared by the process as claimed in claim 8, wherein said composition may contain or more pharmaceutically acceptable excipients.

19. The sugar free sustained release composition as claimed in claim 18, wherein the composition is formulated as oral liquid suspension.