DESC:TECHNICAL FIELD OF INVENTION

The invention relates to a pharmaceutical compositions comprising pidotimod or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients. The invention provides taste masked pharmaceutical composition having desired storage stability. Further, the invention also provides process for preparing pharmaceutical composition of pidotimod or pharmaceutically acceptable salt thereof.

BACKGROUND OF THE INVENTION

Immunotherapy is the treatment of disease by inducing, enhancing or suppressing an immune response. Immunotherapies intended to elicit or increase an immune response are classified as activation immunotherapies, while immunotherapies that suppress immune response are classified as suppression immunotherapies.

Pidotimod is a safe immunomodulant, its chemical structure shows a sulfur ring attached to Piracetam. A piracitam is a cyclic derivative of gamma-aminobutyric acid (GABA). The pidotimod has chemical name (4R)-3-[[(2S)-5-Oxo-2-pyrrolidinyl]carbonyl]-4-thiazolidine carboxylic acid and has the structural formula:

Formula I

Pidotimod is a synthetic dipeptide molecule with immunomodulatory properties.

The US 5,369,131 patent relates to a liquid pharmaceutical composition of pidotimod.

The CN 102525903 patent relates to an oral liquid preparation of pidotimod and its use to promote the body's immune response.

The CN 102525902 patent relates to a high concentration of pidotimod oral liquid preparations used to promote the body's immune response.

The CN 102166183 patent relates to immunologic stimulant oral syrup compositions comprising pidotimod, sucrose, pH regulator, ethyl hydroxyl benzoate, ethanol, essence and purified water.

The US 8,263,125 patent relates to a dosage form for high dose-high solubility active ingredients that provides for immediate release and modified release of the active ingredients.

The prior art teaches various dosage forms and process for preparation of pidotimod composition, but still there exist a need to develop a formulation having desired storage stability and improved taste which provides better patients compliance.

Oral administration is the most favorable route of drug delivery for both patients and its manufacturers. Many potential hydrophilic drugs administrated orally exhibit low oral bioavailability mainly due to their low intestinal permeability. For this kind of drugs, defined as high solubility/low permeability class or it is classified as class III according to biopharmaceutical classification system (BCS). Gastrointestinal permeation is the rate-controlling step in the absorption process. Orally administered pharmaceutical compositions are provided to patients in many dosage forms, including solid forms such as capsules, caplets or tablets and liquid forms such as solutions and suspensions.

The inventors of this invention surprisingly found that it is possible to develop oral liquid composition of pidotimod having desired storage stability and improved taste by using one or more sweeteners and alkalizers in the formulation.

SUMMARY OF THE INVENTION

The invention relates to a stable liquid pharmaceutical composition for oral administration comprising pidotimod or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients. By using specific pharmaceutical acceptable excipients, the invention provides composition having desired storage stability and improved taste of the composition. The invention also provides process for preparing pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.

In one general aspect, there is provided a pharmaceutical composition comprising a) pidotimod or pharmaceutically acceptable salt thereof; b) one or more alkalizers; and one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a stable liquid pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients, wherein the composition provides desired storage stability and improved taste.

In another general aspect, there is provided a stable liquid pharmaceutical composition for oral administration comprising pidotimod or pharmaceutically acceptable salt thereof and one or more alkalizer or combination thereof.

In another general aspect, there is provided a stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof and one or more alkalizer or combination thereof, wherein alkalizer can be tromethamine or sodium hydroxide.

In another general aspect, there is provided a stable pharmaceutical composition comprising a) pidotimod or pharmaceutically acceptable salt thereof; b) one or more alkalizer and, c) other pharmaceutical acceptable excipients comprising sweetener, viscosity modifier, pH modulator, stabilizer, flavoring agent, vehicle or solvent, surfactant, chelating agent.

In another general aspect, there is provided a stable liquid pharmaceutical composition comprising a) 5.71% w/v of pidotimod or pharmaceutically acceptable salt thereof; b) one or more alkalizer and c) other pharmaceutical excipients comprising sweetener, viscosity modifier, pH modulator, stabilizer, flavoring agent, vehicle or solvent, surfactant, chelating agent.

In another general aspect, there is provided a stable liquid pharmaceutical composition comprising a) 5.71% w/v of pidotimod or pharmaceutically acceptable salt thereof; b) 0.1%-1.05% w/v tromethamine or sodium hydroxide and c) other pharmaceutically acceptable excipients.

In another general aspect, there is provided a stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof in combination with or without any additional active ingredient and one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients, wherein amount of pidotimod present in the composition is about 5.71% w/v of the composition.

In another general aspect, there is provided a stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the viscosity modifier is present in amount ranges from about 33.0% w/v to about 65.0 % w/v of the composition.

In another general aspect, there is provided a stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the stabilizer is present is present in amount ranges from about 0.005% w/v to about 1.5 % w/v of the composition.

In another general aspect, there is provided a stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the flavoring agent is present is present in amount ranges from about 0.005% w/v to about 0.25 % w/v of the composition.

In another general aspect, there is provided a stable pharmaceutical composition comprising a) 5.71 % pidotimod or pharmaceutically acceptable salt thereof; b) 0.1-1.05% tromethamine or sodium hydroxide or combination thereof; c) 30% liquid glucose; and d) one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a stable pharmaceutical composition comprising a) 5.71 % w/v pidotimod or pharmaceutically acceptable salt thereof; b) 0.1% w/v tromethamine or 0.95 % w/v sodium hydroxide or combination thereof; c) 30% w/v liquid glucose; and d) one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a stable pharmaceutical composition comprising a) 5.71 % w/v pidotimod or pharmaceutically acceptable salt thereof; b) 0.1% w/v tromethamine or 0.90 % w/v sodium hydroxide or combination thereof; c) 30% w/v liquid glucose; and d) one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a stable pharmaceutical composition comprising a) 5.71 % w/v pidotimod or pharmaceutically acceptable salt thereof; b) 0.15% w/v tromethamine or 0.90 % w/v sodium hydroxide or combination thereof; c) 30% w/v liquid glucose; and d) one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a stable pharmaceutical composition comprising a) 5.71 % w/v pidotimod or pharmaceutically acceptable salt thereof; b) 0.15% w/v tromethamine or 0.95 % w/v sodium hydroxide or combination thereof; c) 30% w/v liquid glucose; and d) one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a stable pharmaceutical composition comprising a) 5.71 % pidotimod or pharmaceutically acceptable salt thereof; b) 0.1% tromethamine; c) 0.95% sodium hydroxide; d) 30% liquid glucose; e) 5% sorbitol solution; f) 0.010% disodium edetate; g) 0.2% sucralose; h) 0.1% flavouring agent; i) 50% glycerine and j) purified water as vehicle.

In another general aspect, there is provided a stable pharmaceutical composition comprising a) 5.71 % pidotimod or pharmaceutically acceptable salt thereof; b) 0.1% tromethamine; c) 0.90% sodium hydroxide; d) 30% liquid glucose; e) 5% sorbitol solution; f) 0.010% disodium edetate; g) 0.2% sucralose; h) 0.1% flavouring agent; i) 50% glycerine and j) purified water as vehicle.

In another general aspect, there is provided a stable pharmaceutical composition comprising a) 5.71 % pidotimod or pharmaceutically acceptable salt thereof; b) 0.15% tromethamine; c) 0.95% sodium hydroxide; d) 30% liquid glucose; e) 5% sorbitol solution; f) 0.010% disodium edetate; g) 0.2% sucralose; h) 0.1% flavouring agent; i) 50% glycerine and j) purified water as vehicle.

In another general aspect, there is provided a stable pharmaceutical composition comprising a) 5.71 % pidotimod or pharmaceutically acceptable salt thereof; b) 0.15% tromethamine; c) 0.90% sodium hydroxide; d) 30% liquid glucose; e) 5% sorbitol solution; f) 0.010% disodium edetate; g) 0.2% sucralose; h) 0.1% flavouring agent; i) 50% glycerine and j) purified water as vehicle.

In another general aspect, there is provided a stable liquid pharmaceutical composition comprising a) 5.71 % pidotimod or pharmaceutically acceptable salt thereof; b) 0.1% tromethamine; c) 0.95% sodium hydroxide; d) 30% liquid glucose; e) 5% sorbitol solution; and one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the composition shows desired storage stability when stored at a temperature of 40°C and 75% relative humidity for a period of at least 6 months.

In another general aspect, there is provided a stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the composition is in the form of oral liquid dosage form.

In another general aspect, there is provided a process for preparing stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a process for preparing stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the process comprises steps such as mixing, dissolving, filtering, stirring, heating.

In another general aspect, there is provided a process for preparing stable liquid pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the process comprises:
(a) Prepare solution comprising sweeteners and viscosity modifying agent;
(b) Dissolve stabilizer or alkalizer separately in purified water and mixing of these solutions in to solution obtained in step (a) to get solution;
(c) mix active ingredient to a solution obtained in step (b) and stir it to obtain clear solution;
(d) adjust pH of step (c) solution;
(e) prepare additional sweetener solution in purified water and adding to step (d) solution;
(f) Add flavoring agent to a solution obtained in step (e); and
(g) Make volume up to 100ml and filtering of a solution obtained in step (f).

In another general aspect, there is provided a process for preparing stable liquid pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the process comprises:
(a) Prepare solution comprising sweeteners and viscosity modifying agent;
(b) Dissolve stabilizer or alkalizer separately in purified water and mixing of these solutions in to solution obtained in step (a) to get solution;
(c) mix active ingredient to a solution obtained in step (b) solution and stir it to obtain clear solution;
(d) adjust pH of a solution obtained in step (c);
(e) prepare additional sweetener solution in purified water and adding to a solution obtained in step (d);
(f) Add flavoring agent to a solution obtained in step (e), filter this syrup through 200# nylon cloth and Make volume up to 100ml.

In another general aspect, there is provided a process for preparing stable liquid pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the process comprises:
(a) Prepare solution comprising liquid glucose and glycerin;
(b) Dissolve Disodium edetate or tromethamine separately in purified water and mixing of these solutions in to solution obtained in step (a) to get solution;
(c) mix pidotimod to a solution obtained in step (b) solution and stir it to obtain clear solution;
(d) adjust pH of a solution obtained in step (c);
(e) prepare additional sweetener solution in purified water and add it to a solution obtained in step (d);
(f) Add flavoring agent to a solution obtained in step (e), filter this syrup through 200# nylon cloth and make volume up to 100ml.

DETAILED DESCRIPTION OF THE INVENTION

The term "active ingredient" refers to a therapeutically active compound in its free form (base), pharmaceutically acceptable salt, hydrates, solvates and its prodrugs.

The term “pidotimod” as used herein refers not only its free form (base) but also refers to its salt, solvates, prodrugs, hydrates, enantiomers or polymorphs thereof.

The term "stable" as used herein refers to physical and chemical stability of pidotimod or pharmaceutically acceptable salt thereof with another pharmaceutical active agent for oral liquid composition.

The term "treatment" refers to the medical management of a patient with the intent to cure, ameliorate, stabilize, or prevent a disease, pathological condition, or disorder.

The term “desired time period” refers to duration of time for stability studies, which is not less than 6 months.

The term "excipients" as used herein means a component of a pharmaceutical product that is not an active ingredient may include, but are not limited to antioxidants, alkalizers, humectants, defoaming agents, chelating agents, preservatives, solubilizers, buffers, electrolytes, sweeteners, viscosity modifier, syrup base, flavours, colours, solvents such as purified water, co-solvents, taste masking agents and/or mixture thereof. The excipients that are useful in preparing a pharmaceutical composition are preferably safe, non-toxic and neither biologically nor otherwise undesirable, and are acceptable for pharmaceutical use.

The present oral compositions comprise a sugar and/or other sweetener to provide sweetness and taste masking of pharmaceutical active(s) as well as to provide some body and thickness. Sucrose, glucose or table sugar, often in liquid form, may be used. Alternatively, or additionally if greater sweetening is desired, sugar alcohols such as glycerin, sorbitol, maltitol, and mannitol can be used to provide sweetness.

Sweetness levels can also be supplemented with the use of an artificial sweetener. Non-limiting examples of artificial sweeteners are selected from sodium saccharine, acesulfame potassium, sucralose, aspartame, monoammonium glycyrrhizinate, neohesperidin dihydrochalcone, thaumatin, neotame, cyclamates, liquid glucose, sorbitol solution and mixtures thereof. Generally, such artificial sweeteners are solids when used in sweetening compositions.

Examples of suitable flavoring agents include, but are not limited to, natural and artificial flavors such as mints (i.e., peppermint, etc.), menthol, chocolate, artificial chocolate, bubblegum, both artificial and natural fruit flavors (i.e., cherry, grape, orange, blue berry, strawberry, etc.) and combinations of two or more thereof. Flavoring agents are generally provided as a minor component of the composition in amounts effective to provide palatable flavor to the compositions. Typically, flavoring agents are present in amounts in the range of about 0 grams to about 5 grams per 100 ml of the composition. Preferably menthol, essence mixed fruit VSA S 2535 (IFF) and flavor RSW 786 can be used.

Examples of suitable alkalizer/alkaline earth metal salts include, but not limited to calcium carbonate, calcium hydroxide, magnesium carbonate, magnesium hydroxide, magnesium silicate, magnesium aluminate or aluminum magnesium hydroxide, sodium hydroxide, sodium chloride, tromethamine.

Antioxidants which are effective according to the invention as stabilizers include, but not limited to diamylhydroquinone, di-tert-butylhydroquinone, dicetyl thiodipropionate, digalloyl trioleate, dilauryl thiodipropionate, dimyristyl thiodipropionate, dioleyltocopherylmethylsilanol, disodium rutinyldisulphate, disodium edetate, distearyl thiodipropionate, ditridecyl thiodipropionate, dodecyl gallate, erythorbic acid, ethyl ferulate, ferulic acid, hydroquinone.

Suitable viscosity modifying agents include but are not limited to chitosan, xanthan, hydroxpropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), hydroxyethylcellulose (HEC), glycerin, polyvinyl alcohol, glactomannons such as guar, konjac, locust bean gum and mamman, for example, microcrystalline cellulose and combinations thereof.

In one embodiment, there is provided a stable pharmaceutical composition comprising a) pidotimod or pharmaceutically acceptable salt thereof; b) one or more alkalizers; and one or more pharmaceutically acceptable excipients.

In further embodiment, there is provided a stable liquid pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the composition provides improved taste of pidotimod by using alkalizer or its combination. The present formulation is stable in photostability study & freeze thaw study.

In further embodiment, there is provided a stable liquid pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof and one or more alkalizer or combination thereof, wherein alkalizer can be tromethamine or sodium hydroxide.

In further embodiment, there is provided a stable pharmaceutical composition comprising pidotimod in combination with or without any additional active ingredient or pharmaceutically acceptable salt thereof, wherein the composition provides improved taste of pidotimod by using alkalizer or its combination.

In further embodiment, there is provided a stable liquid pharmaceutical composition for oral administration comprising pidotimod or pharmaceutically acceptable salt thereof, wherein amount of pidotimod present in composition is about 5.71 % w/v of the solution.

In further embodiment, there is provided a stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the viscosity modifier is present in amount ranges from about 33.0 % w/v to about 65.0 % w/v of the solution.

In further embodiment, there is provided a stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the stabilizer is present is present in amount ranges from about 0.005% w/v to about 1.5 % w/v of the solution.

In further embodiment, there is provided a stable liquid pharmaceutical composition comprising a) 5.71% w/v of pidotimod or pharmaceutically acceptable salt thereof; b) one or more alkalizer and, c) other pharmaceutical excipients comprising sweetener, viscosity modifier, pH modulator, stabilizer, flavoring agent, vehicle or solvent, surfactant, chelating agent.

In further embodiment, there is provided a stable pharmaceutical composition comprising a) 5.71% w/v of pidotimod or pharmaceutically acceptable salt thereof; b) 0.1%-1.05% w/v tromethamine or sodium hydroxide and, c) other pharmaceutically acceptable excipients.

In further embodiment, there is provided a stable pharmaceutical composition comprising a) 5.71% w/v of pidotimod or pharmaceutically acceptable salt thereof; b) 0.95% sodium hydroxide and or 0.1% w/v tromethamine, c) other pharmaceutically acceptable excipients.

In further embodiment, there is provided a stable pharmaceutical composition comprising a) 5.71 % pidotimod or pharmaceutically acceptable salt thereof; b) 0.1-1.05% tromethamine or sodium hydroxide or combination thereof; c) 30% liquid glucose; and d) one or more pharmaceutically acceptable excipients.

In further embodiment, there is provided a stable pharmaceutical composition comprising a) 5.71 % w/v pidotimod or pharmaceutically acceptable salt thereof; b) 0.1% w/v tromethamine or 0.95 % w/v sodium hydroxide or combination thereof; c) 30% w/v liquid glucose; and d) one or more pharmaceutically acceptable excipients.

In further embodiment, there is provided a stable pharmaceutical composition comprising a) 5.71 % w/v pidotimod or pharmaceutically acceptable salt thereof; b) 0.1% w/v tromethamine or 0.90 % w/v sodium hydroxide or combination thereof; c) 30% w/v liquid glucose; and d) one or more pharmaceutically acceptable excipients.

In further embodiment, there is provided a stable pharmaceutical composition comprising a) 5.71 % w/v pidotimod or pharmaceutically acceptable salt thereof; b) 0.15% w/v tromethamine or 0.90 % w/v sodium hydroxide or combination thereof; c) 30% w/v liquid glucose; and d) one or more pharmaceutically acceptable excipients.

In further embodiment, there is provided a stable pharmaceutical composition comprising a) 5.71 % w/v pidotimod or pharmaceutically acceptable salt thereof; b) 0.15% w/v tromethamine or 0.95 % w/v sodium hydroxide or combination thereof; c) 30% w/v liquid glucose; and d) one or more pharmaceutically acceptable excipients.

In further embodiment, there is provided a stable pharmaceutical composition comprising a) 5.71 % pidotimod or pharmaceutically acceptable salt thereof; b) 0.1% tromethamine; c) 0.95% sodium hydroxide; d) 30% liquid glucose; e) 5% sorbitol solution; f) 0.010% disodium edetate; g) 0.2% sucralose; h) 0.1% flavouring agent; i) 50% glycerine and j) purified water as vehicle.

In another embodiment, there is provided a stable pharmaceutical composition comprising a) 5.71 % pidotimod or pharmaceutically acceptable salt thereof; b) 0.1% tromethamine; c) 0.90% sodium hydroxide; d) 30% liquid glucose; e) 5% sorbitol solution; f) 0.010% disodium edetate; g) 0.2% sucralose; h) 0.1% flavouring agent; i) 50% glycerine and j) purified water as vehicle.

In further embodiment, there is provided a stable pharmaceutical composition comprising a) 5.71 % pidotimod or pharmaceutically acceptable salt thereof; b) 0.15% tromethamine; c) 0.95% sodium hydroxide; d) 30% liquid glucose; e) 5% sorbitol solution; f) 0.010% disodium edetate; g) 0.2% sucralose; h) 0.1% flavouring agent; i) 50% glycerine and j) purified water as vehicle.

In further embodiment, there is provided a stable pharmaceutical composition comprising a) 5.71 % pidotimod or pharmaceutically acceptable salt thereof; b) 0.15% tromethamine; c) 0.90% sodium hydroxide; d) 30% liquid glucose; e) 5% sorbitol solution; f) 0.010% disodium edetate; g) 0.2% sucralose; h) 0.1% flavouring agent; i) 50% glycerine and j) purified water as vehicle.

In further embodiment, there is provided a stable liquid pharmaceutical composition comprising a) 5.71 % pidotimod or pharmaceutically acceptable salt thereof; b) 0.1% tromethamine; c) 0.95% sodium hydroxide; d) 30% liquid glucose; e) 5% sorbitol solution; and one or more pharmaceutically acceptable excipients.

In further embodiment, there is provided a stable pharmaceutical composition comprising pidotimod in combination with or without any additional active ingredient or pharmaceutically acceptable salt thereof, wherein the flavoring agent is present is present in amount ranges from about 0.005% w/v to about 0.25 % w/v of the solution.

In further embodiment, there is a provided a stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the composition is oral liquid composition.

In further embodiment, there is provided process for preparing stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof which comprises steps of mixing, dissolving, filtering, stirring, heating etc.

In further general aspect, there is provided a process for preparing stable liquid pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the process comprises:
(a) Prepare solution comprising sweeteners and viscosity modifying agent;
(b) Dissolve stabilizer or alkalizer separately in purified water and mixing of these solutions in to solution obtained in step (a) to get solution;
(c) mix active ingredient to a solution obtained in step (b) and stir it to obtain clear solution;
(d) adjust pH of step (c) solution;
(e) prepare additional sweetener solution in purified water and adding to step (d) solution;
(f) Add flavoring agent to a solution obtained in step (e); and make volume up to 100ml and filtering of a solution obtained in step.

In further embodiment, there is provided a process for preparing stable liquid pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the process comprises:
(a) Prepare of solution comprising sweeteners and viscosity modifying agent;
(b) Dissolve of stabilizer or alkalizer separately in purified water and mixing of these solutions in to solution obtained in step (a) to get solution;
(c) mix active ingredient to a solution obtained in step (b) solution and stir it to obtain clear solution;
(d) adjust pH of a solution obtained in step (c);
(e) prepare additional sweetener solution in purified water and adding to a solution obtained in step (d);
(f) Add flavoring agent to a solution obtained in step (e), filter this syrup through 200# nylon cloth and make volume up to 100ml.

In further embodiment, there is provided a process for preparing stable liquid pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the process comprises:
(a) Prepare solution comprising liquid glucose and glycerin;
(b) Dissolve disodium edetate or tromethamine separately in purified water and mixing of these solutions in to solution obtained in step (a) to get solution;
(c) mix pidotimod to a solution obtained in step (b) solution and stir it to obtain clear solution;
(d) adjust pH of a solution obtained in step (c);
(e) prepare additional sweetener solution in purified water and add it to a solution obtained in step (d);
(f) Add flavoring agent to a solution obtained in step (e), filter this syrup through 200# nylon cloth and Make volume up to 100ml.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

This invention is further illustrated by the following examples which are provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of this invention.

The invention now will be described in particularity with the following illustrative examples; however, the scope of the invention is not intended to be and shall not be limited to the exemplified embodiments below.

Examples
Example 1: Pidotimod composition
Table 1
Sr. No. Ingredients Quantity
(% w/v)
1 Pidotimod 5.71
2 Glycerin 44.0
3 Liquid glucose 34.0
4 Sorbitol solution (70%) (Non Crystallizing) 5.5
5 Tromethamine 0.15
6 Sodium Hydroxide 0.90
7 Disodium Edetate 0.01
8 Sucralose 0.15
9 Blue berry FLV 7030 0.10
10 Purified Water q.s to
100 ml
Total quantity (ml) 100

Process:
(a) Mix glycerin and sorbitol solution in a suitable vessel and heat the mixture to 50-60°C under stirring. Then add liquid glucose and continue stirring till uniform solution is obtained. Then allow cooling this solution below 35°C.
(b) In separate container dissolve disodium edetate in previously heated Purified Water under stirring. Add this solution to step (a) solution & mix for 5 min.
(c) Dissolve tromethamine (tris buffer) in purified water in suitable vessel under stirring. Add this solution to step (b) solution & mix for 5 min.
(d) Dissolve sodium hydroxide in purified water in suitable vessel under stirring. Allow to cool this solution below 35°C. Add this solution to step (c) solution & mix for 5 min.
(e) Transfer pidotimod in step (d) solution under stirring up to 15 minutes to obtain clear solution.
(f) Dissolve sodium hydroxide in purified water in suitable vessel under stirring. Allow to cool this solution below 35°C.
(g) Adjust pH of step (e) solution up to 5±0.3 by using step (f) solution
(h) Dissolve sucralose in purified water in suitable vessel under stirring. Add this solution to step (g) solution & mix for 5 min.
(i) Add blue berry flavour to step (h) solution & mix for 5 min and make up the volume to 100% with purified water & mix for 10 min. and filter this syrup & fill in 100 ml Bottles.

Example 2: Pidotimod composition
Table 2
Sr. No. Ingredients Quantity
(% w/v)
1 Pidotimod 5.71
2 Glycerin 54.0
3 Liquid glucose 27.0
4 Sorbitol solution (70%) (Non Crystallizing) 4.0
5 Tromethamine 0.10
6 Sodium Hydroxide 0.95
7 Disodium Edetate 0.01
8 Sucralose 0.15
9 Blue berry FLV 7030 0.10
10 Purified Water q.s to
100 ml
Total quantity (ml) 100

Process:
(a) Mix glycerin and sorbitol solution in a suitable vessel and heat the mixture to 50-60°C under stirring. Then add liquid glucose and continue stirring till uniform solution is obtained. Then allow cooling this solution below 35°C.
(b) In separate container dissolve disodium edetate in previously heated Purified Water under stirring. Add this solution to step (a) solution & mix for 5 min.
(c) Dissolve tromethamine (tris buffer) in purified water in suitable vessel under stirring. Add this solution to step (b) solution & mix for 5 min.
(d) Dissolve sodium hydroxide in purified water in suitable vessel under stirring. Allow to cool this solution below 35°C. Add this solution to step (c) solution & mix for 5 min.
(e) Transfer pidotimod in step (d) solution under stirring up to 15 minutes to obtain clear solution.
(f) Dissolve sodium hydroxide in purified water in suitable vessel under stirring. Allow to cool this solution below 35°C.
(g) Adjust pH of step (e) solution up to 5±0.3 by using step (f) solution
(h) Dissolve sucralose in purified water in suitable vessel under stirring. Add this solution to step (g) solution & mix for 5 min.
(i) Add blue berry flavour to step (h) solution & mix for 5 min and make up the volume to 100% with purified water & mix for 10 min. and filter this syrup & fill in 100 ml Bottles.

,CLAIMS:1. A pharmaceutical composition comprising a) pidotimod or pharmaceutically acceptable salt thereof; b) one or more alkalizers; and one or more pharmaceutically acceptable excipients.

2. The pharmaceutical composition according to claim 1, wherein the one or more alkalizers comprises tromethamine or sodium hydroxide or combination thereof.

3. The pharmaceutical composition according to claim 2, wherein the tromethamine is present in an amount of 0.1% or 0.15% of the composition.

4. The pharmaceutical composition according to claim 2, wherein the sodium hydroxide is present in an amount of 0.90% or 0.95% of the composition.

5. A pharmaceutical composition comprising a) 5.71% pidotimod or pharmaceutically acceptable salt thereof; b) 0.1-1.05% tromethamine or sodium hydroxide or combination thereof; c) 30% liquid glucose; and d) one or more pharmaceutically acceptable excipients.

6. The pharmaceutical composition according to claim 5, wherein one or more pharmaceutically acceptable excipients are selected from the group consisting of sweetener, viscosity modifier, stabilizer, flavouring agent, vehicle or solvent, surfactant, chelating agent or combination thereof.

7. The pharmaceutical composition according to claim 1 or 5 wherein the said pharmaceutical composition is in the form of liquid dosage form.

8. A pharmaceutical composition comprising a) 5.71% pidotimod or pharmaceutically acceptable salt thereof; b) 0.1% tromethamine; c) 0.95% sodium hydroxide; d) 30% liquid glucose; e) 5% sorbitol solution; f) 0.010% disodium edetate; g) 0.2% sucralose; h) 0.1% flavouring agent; i) 50% glycerine and j) purified water as vehicle.

9. The pharmaceutical composition according to claim 8, wherein the said pharmaceutical composition is in the form of liquid dosage form.

10. A liquid pharmaceutical composition comprising a) 5.71 % pidotimod or pharmaceutically acceptable salt thereof; b) 0.1% tromethamine; c) 0.95% sodium hydroxide; d) 30% liquid glucose; e) 5% sorbitol solution; and one or more pharmaceutically acceptable excipients.