DESC:TECHNICAL FIELD OF INVENTION

The invention relates to process for preparing a stable pharmaceutical compositions comprising pidotimod or pharmaceutically acceptable salt thereof. The invention provides compositions having desired storage stability.

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 contains 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 and it is hydrophilic in nature, it absorbs moisture from atmosphere and get soften during stability studies. Pidotimod was approved in China for infections of the respiratory system in secondary and primary immunodeficiency with alteration in maturation of T cells in adults only.

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. It relates to a dosage form of combination of high dose high solubility active ingredient like pidotimod as modified release and low dose active ingredient as immediate release suitable for swallowing of dosage form.

The Chinese patent CN 101612152 relates to pidotimod-containing pharmaceutical composition and a preparation method thereof.

The Chinese patent CN 102327243 relates to pidotimod chewable tablet, which is composed by pidotimod and auxiliary materials.

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

The US 4,839,387 patent describes pharmaceutical composition of pidotimod.

The Chinese patent CN 1868464 relates to pidotimod soft capsule and its preparation.

At present, the major oral dosage forms are tablets, conventional tablets in vivo plasma concentration cannot show a smooth steady release characteristics and good water solubility pidotimod tablet is easy to absorb moisture, thus affecting drugs formulation stability.

The prior art teaches various dosage forms and process for preparation of pidotimod composition, but there exist a need to develop a composition having better moisture protection to get desired storage stability.

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 the invention surprisingly found that it is possible to develop composition having desired storage stability and better moisture protection.

SUMMARY OF THE INVENTION

The invention relates to process for preparing a pharmaceutical composition for oral administration comprising pidotimod or pharmaceutically acceptable salt thereof with pharmaceutically acceptable excipients which provides desired storage stability and better moisture protection.

In one general aspect, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof and pharmaceutically acceptable excipients or mixture thereof.

In another general aspect, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof and pharmaceutically acceptable excipients or mixture thereof, which further compressed in to solid dosage form.

In another general aspect, there is provided a pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof and pharmaceutically acceptable excipients or mixture thereof, which further compressed in to solid dosage form.

In another general aspect, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof and pharmaceutically acceptable excipients or mixture thereof, which is compressed in to solid dosage form and further coated with suitable coating material to get desired moisture protection.

In another general aspect, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof and pharmaceutically acceptable excipients, wherein pharmaceutically acceptable excipients comprises fillers or diluents, binders, disintegrants and/or superdisintegrants, sorbents, antiadherents, lubricants, glidants, preservatives, flavoring agents, colouring agent, coating agent, solvents or vehicles or combination thereof.

In another general aspect, there is provided a process for the preparation of pharmaceutical composition comprising a) 60-80% pidotimod or pharmaceutically acceptable salt thereof; b) 1-3% maize starch; c) 1-6% binder; d) one or more coating and one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a pharmaceutical composition comprising a) 60-80% pidotimod or pharmaceutically acceptable salt thereof; b) 1-3% maize starch; c) 1-6% binder; d) one or more coating and one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a process for preparation of solid pharmaceutical composition comprising a) a core comprising pidotimod or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients; b) coating layer over said core comprising ethyl cellulose; c) one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein amount of pidotimod present in ranges from about 40% w/w to about 85% w/w of the composition.

In another general aspect, there is provided a process for preparation of solid pharmaceutical composition comprising a) a core comprising 65-75% w/w of pidotimod or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients; b) coating layer over said core comprising ethyl cellulose; c) one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the filler/diluent is present in amount ranges from about 5.0 % w/w to about 25 % w/w of the composition.

In another general aspect, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein binder is present in amount ranges from about 1.0% w/w to about 12 % w/w of the composition.

In another general aspect, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the glidant is present in amount ranges from about 0.25 % w/w to about 2 % w/w of the composition.

In another general aspect, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the lubricant is present in amount ranges from about 0.25 % w/w to about 3.0% w/w of the composition.

In another general aspect, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the coating material is present in amount ranges from about 1.0 % w/w to about 7.0 % w/w of the composition.

In another general aspect, there is provided a process for preparation of solid pharmaceutical composition comprising a) a core comprising 70.61% w/w of pidotimod or pharmaceutically acceptable salt thereof; 9.71% w/w of microcrystalline cellulose; 5.30% w/w/ hydroxypropyl cellulose and one or more pharmaceutically acceptable excipients; b) coating layer over said core comprising ethyl cellulose; and c) one or more pharmaceutically acceptable excipients, wherein the composition provides immediate release of pidotimod from the dosage from.

In another general aspect, there is provided a process for preparation of solid pharmaceutical composition comprising a) a core comprising 70.61% w/w of pidotimod or pharmaceutically acceptable salt thereof; 9.71% w/w of microcrystalline cellulose; 1.32% w/w/ of cross carmellose sodium; 1.32% w/w/ of maize starch; 5.30% w/w/ hydroxypropyl cellulose and one or more pharmaceutically acceptable excipients; b) coating layer over said core comprising ethyl cellulose; and c) one or more pharmaceutically acceptable excipients, wherein the composition provides immediate release of pidotimod from the dosage from.

In another general aspect, there is provided a process for preparation of 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 process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the composition of the present invention is present in the form of powder, tablets, pellets, capsules, granules or pellets filled in capsule, tablet in capsule, multilayer tablet, bilayer tablet, trilayer tablet, minitablets or premixed powder filled in capsule.

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

In another general aspect, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein coating provided to the dosage form with one or more suitable coating agent/ film forming agent or mixture thereof.

In another general aspect, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein coating material comprises ethylcellulose.

In another general aspect, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the composition is tablet dosage form.

In another general aspect, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the composition provides immediate release of pidotimod from the dosage from.

In another general aspect, there is provided a process for preparing a pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein process comprises;
a) sifting of active ingredient and excipients and then loading these material into rapid mixer granulator;
b) preparing binder solution and granulating the ingredients of step (a) by using the solution
c) drying of step (b) material in fluidized bed dryer (FBD);
d) milling of step (c) material;
e) lubricating the step (d) material;
f) compressing the step (e) material to get solid dosage form;
g) coating of dosage unit obtained in step (f).

In another general aspect, there is provided a process of preparing solid pharmaceutical composition comprising steps of:
a) mixing of pidotimod or pharmaceutically acceptable salt thereof with maize starch and optionally with one or more pharmaceutically acceptable excipients;
b) mixing of hydroxypropyl cellulose in to suitable solvent;
c) granulation of material obtained in step (a) with binder solution obtained in step (b);
d) drying, sifting of granulated material obtained in step (c);
e) mixing of material obtained in step (d) with suitable extragranular material and compression to get solid dosage form;
f) application of coating layer over dosage form obtained in step (e).

In another general aspect, there is provided a process of preparing solid pharmaceutical composition comprising steps of:
a) mixing of pidotimod or pharmaceutically acceptable salt thereof with 1-3% maize starch and optionally with one or more pharmaceutically acceptable excipients;
b) mixing of 1-6% hydroxy propyl cellulose in to suitable solvent;
c) granulation of material obtained in step (a) with binder solution obtained in step (b);
d) drying, sifting of granulated material obtained in step (c);
e) mixing of material obtained in step (d) with suitable extragranular material;
f) lubrication of material obtained in step (e) and compression to get tablet dosage form;
g) application of coating layer over tablet obtained in step (f).

In another general aspect, there is provided process for preparing a pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein compression provides solid dosage composition.

In another general aspect, there is provided process for preparing a pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the process provides dosage form is tablet dosage form.

In another general aspect, there is provided process for preparing a pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein process comprises specialized coating which provides protection to the composition from moisture.

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 “immediate release” is meant that the pharmacologically active ingredient or agent is released from the dosage form immediately such that not less than 80% of the pharmaceutically active agent in the formulation is released within 45 minutes when dissolution is measured according to the USP 31 NF 26 section 711.

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

The term "pharmaceutically acceptable excipients" includes a pharmaceutically acceptable material, vehicle, suitable for administering an active pharmaceutical ingredient. Each excipient should be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient.

In one embodiment, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof and pharmaceutically acceptable excipients or mixture thereof, wherein composition is in the form of solid dosage form.

In further embodiment, there is provided a process for preparation of pharmaceutical composition for oral administration comprising pidotimod or pharmaceutically acceptable salt thereof and pharmaceutically acceptable excipients or mixture thereof, which is in the form of compressed dosage form.

In further embodiment, there is provided a process for preparation of pharmaceutical composition for oral administration comprising pidotimod or pharmaceutically acceptable salt thereof and pharmaceutically acceptable excipients or mixture thereof, which is in the form of compressed dosage form and further coated with suitable coating material to get desired moisture protection.

In further embodiment, there is provided a process for the preparation of pharmaceutical composition comprising a) 60-80% pidotimod or pharmaceutically acceptable salt thereof; b) 1-3% maize starch; c) 1-6% binder; d) one or more coating and one or more pharmaceutically acceptable excipients.

In further embodiment, there is provided a pharmaceutical composition comprising a) 60-80% pidotimod or pharmaceutically acceptable salt thereof; b) 1-3% maize starch; c) 1-6% binder; d) one or more coating and one or more pharmaceutically acceptable excipients.

In further embodiment, there is provided a process for preparation of pharmaceutical composition comprises pidotimod or pharmaceutically acceptable salt thereof, wherein the composition is coated with specialized coating material which comprises ethylcellulose.

In further embodiment, there is provided a process for preparation of pharmaceutical composition comprises pidotimod or pharmaceutically acceptable salt thereof, wherein the compressed dosage form may be tablets, tablet in capsule, pellets or granules, pellets filled in capsules, bilayer tablets, minitablet.

In further embodiment, there is provided a process for preparation of pharmaceutical composition comprises pidotimod pharmaceutically acceptable salt thereof, wherein the composition of the present invention is present in the form of powder, capsules, granules or pellets filled in capsule, tablet in capsule, multilayer tablet and premixed powder filled in capsule.

In further embodiment, there is provided process for preparation of solid pharmaceutical composition comprising a) a core comprising pidotimod or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients; b) coating layer over said core comprising ethyl cellulose; c) one or more pharmaceutically acceptable excipients.

In further embodiment, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein amount of pidotimod is about 40 % w/w to about 85% w/w of the formulation.

In further embodiment, there is provided a process for preparation of solid pharmaceutical composition comprising a) a core comprising 65-75% w/w of pidotimod or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients; b) coating layer over said core comprising ethyl cellulose; c) one or more pharmaceutically acceptable excipients.

In further embodiment, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the filler/diluent is present in amount ranges from about 5.0 % w/w to about 25 % w/w of the formulation.

In further embodiment, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the binder is present in amount ranges from about 1.0% w/w to about 12 % w/w of the composition.

In further embodiment, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the glidant is present in amount ranges from about 0.25 % w/w to about 2 % w/w of the composition.

In further embodiment, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the lubricant is present in amount ranges from about 0.25 % w/w to about 3.0 % w/w of the composition.

In further embodiment, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the coating material is present in amount ranges from about 1.0 % w/w to about 7.0 % w/w of the composition.

In further embodiment, there is provided a process for preparation of solid pharmaceutical composition comprising a) a core comprising 70.61% w/w of pidotimod or pharmaceutically acceptable salt thereof; 9.71% w/w of microcrystalline cellulose; 5.30% w/w/ hydroxypropyl cellulose and one or more pharmaceutically acceptable excipients; b) coating layer over said core comprising ethyl cellulose; and c) one or more pharmaceutically acceptable excipients, wherein the composition provides immediate release of pidotimod from the dosage from.

In further embodiment, there is provided a process for preparation of solid pharmaceutical composition comprising a) a core comprising 70.61% w/w of pidotimod or pharmaceutically acceptable salt thereof; 9.71% w/w of microcrystalline cellulose; 1.32% w/w/ of cross carmellose sodium; 1.32% w/w/ of maize starch; 5.30% w/w/ hydroxypropyl cellulose and one or more pharmaceutically acceptable excipients; b) coating layer over said core comprising ethyl cellulose; and c) one or more pharmaceutically acceptable excipients, wherein the composition provides immediate release of pidotimod from the dosage from.

In further embodiment, there is provided a process for preparation of pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein the composition provides immediate release of pidotimod.

In further embodiment, there is provided process for preparing stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein process comprises
a) sifting of active ingredient and pharmaceutically acceptable excipients through sieve and then loading of these material into rapid mixer granulator;
b) preparing binder solution and granulating the step (a) material by using this solution
c) drying of prepared granules in fluidized bed dryer;
d) milling of the dried granules;
e) lubricating the milled granules;
f) compressing to get solid dosage form;
g) coating of solid dosage form.

In further embodiment, there is provided process for preparing stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein process comprising direct compression of active ingredient and pharmaceutical acceptable excipients which comprises:
a) sifting of active ingredient and pharmaceutically acceptable excipients;
b) mixing of step (a) material;
c) compression to get solid dosage form.

In further embodiment, there is provided process for preparing stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein process comprising direct compression of active ingredient and pharmaceutical acceptable excipients which comprises:
a) sifting of active ingredient and pharmaceutically acceptable excipients;
b) mixing of step (a) material;
c) compression to get solid dosage form;
d) coating of solid dosage form.

In further embodiment, there is provided a process of preparing solid pharmaceutical composition comprising steps of:
a) mixing of pidotimod or pharmaceutically acceptable salt thereof with maize starch and optionally with one or more pharmaceutically acceptable excipients;
b) mixing of hydroxy propyl cellulose in to suitable solvent;
c) granulation of material obtained in step (a) with binder solution obtained in step (b);
d) drying, sifting of granulated material obtained in step (c);
e) mixing of material obtained in step (d) with suitable extragranular material and compression to get solid dosage form;
f) application of coating layer over dosage form obtained in step (e).

In further embodiment, there is provided a process of preparing solid pharmaceutical composition comprising steps of:
a) mixing of pidotimod or pharmaceutically acceptable salt thereof with 1-3% maize starch and optionally with one or more pharmaceutically acceptable excipients;
b) mixing of 1-6% hydroxy propyl cellulose in to suitable solvent;
c) granulation of material obtained in step (a) with binder solution obtained in step (b);
d) drying, sifting of granulated material obtained in step (c);
e) mixing of material obtained in step (d) with suitable extragranular material;
f) lubrication of material obtained in step (e) and compression to get tablet dosage form;
g) application of coating layer over tablet obtained in step (f).

In further embodiment, the coating material comprises one or more coating agents selected from hydroxylpropyl methylcellulose, diethyl phthalate, ethyl cellulose, talc, titanium dioxide or mixture thereof (Insta Moistshield IC-MS-1031).

In further embodiment, there is provided process for preparing stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein compression provides solid dosage composition.

In further embodiment, there is provided process for preparing stable pharmaceutical composition comprising pidotimod or pharmaceutically acceptable salt thereof, wherein process comprises specialized coating over drug containing core which provides protection to the composition from moisture.

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

Examples of the fillers or diluents suitable for use in the composition of the present invention may comprises but are not limited to starches, such as potato starch, rice starch, maize starch, wheat starch, pregelatinized starch, fully pregelatinized starch, cellulose, such as microcrystalline cellulose or silicified microcrystalline cellulose, mannitol, erythritol, calcium salts, such as calcium hydrogen phosphate dihydrate, anhydrous dibasic calcium phosphate, xylitol, sorbitol, lactose monohydrate, magnesium stearate, mannitol or mixtures thereof.

Examples of the disintegrants suitable for use in the composition of the present invention comprises, but are not limited to alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, crosscarmellose sodium, crospovidone, guar gum, magnesium aluminum silicate, maize starch, methyl cellulose, microcrystalline cellulose, polacrilin potassium, powdered cellulose, pregelatinized starch, sodium alginate, sodium starch glycolate and starch.

Examples of the binder suitable for use in the composition of the present invention may comprises but are not limited to polyvinyl pyrrolidone (povidone), copolymers of vinylpyrrolidone with other vinylderivatives (copovidone), hydroxypropyl cellulose, methylcellulose, hydroxypropyl methylcellulose (hypromellose), powdered acacia, gelatin, guar gum and carbomer such as carbopol, polymethacrylates and starch or mixtures thereof.

Examples of the lubricant/glidant suitable for use in the composition of the present invention may comprises from group, but are not limited to stearic acid, talc, siliconised talc, colloidal silicone dioxide, micronised talc, sodium stearyl fumarate and magnesium stearate. Preferable lubricant/glidants is magnesium stearate or mixtures thereof.

Example of coating material use in the composition comprising, but not limited to water-insoluble or water-resistant coating polymers comprising ethyl cellulose, polyvinyl acetates, polyacrylates, polymethacrylates, polyvinyl alcohol, hydroxylpropyl methylcellulose (HPMC) or low viscosity HPMC polymer, Diethyl Phthalate, talc, Titanium Dioxide, Polyvinylpyrrolidone (PVP), hydroxypropyl cellulose (HPC), hydroxypropyl ethyl cellulose (HPEC), polyethylene glycol (PEG) and hydroxyethyl cellulose (HEC) or combination thereof.

Solvent is a substance that can chemically different liquid, solid or gas. Examples of solvent suitable for use in oral pharmaceutical composition may be comprises, but not limited to purified water, isopropyl alcohol, dichloromethane, glycerol, propylene glycol, ethanol, chlordiazepoxide hydrochloride or mixture thereof.

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.

The present 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 the present invention.

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

Examples
Example 1: Pidotimod composition
Table 1
S.No Ingredients Qty/Tablet (%w/w)
Intragranular
1. Pidotimod 70.61
2. Micro Crystalline Cellulose 8.0
3. Cross Carmellose Sodium 1.6
4. Maize Starch 0.7
Binder
5. Hydroxy Propyl cellulose 6.5
6. IPA: Water (80:20) q.s.
Extra Granular
7. Cross Carmellose Sodium 4.0
8. Low Substituted Hydroxy Propyl Cellulose 0.9
9. Colloidal Silicone Dioxide 0.65
10. Magnesium Stearate 1.05
Coating
11. Hydroxypropyl Methylcellulose 1.456
12. Diethyl Phthalate 0.349
13. Ethyl Cellulose 0.262
14. Talc 0.116
15. Titanium Dioxide 0.728
16. Isopropyl Alcohol q.s.
17. Dichloromethane q.s.
Total 100

Process:
(a) All Intragranular ingredients were sifted through sieve and loaded into rapid mixer granulator (RMG);
(b) binder solution was prepared by adding Hydroxypropyl cellulose to isopropyl alcohol (IPA), water mixture under stirring and material from step (a) was granulated by using this solution;
(c) granulated material of step (b) was loaded into fluidized bed dryer (FBD) and dried at 55°C till loss on drying (LOD) obtained not more than 1.5%;
(d) dried granular material of step (c) was passed through sieve and retained material was milled using multi mill;
(e) all extragranular material except magnesium Stearate were passed through sieve and blended with dried material;
(f) magnesium Stearate was passed through sieve, added to step (e) blend;
(g) above blend was compressed to obtain tablets;
(h) coating solution was prepared by the addition of coating material (Insta Moistshield) to IPA under stirring followed by dichloromethane; and
(i) compressed tablets of step (g) were coated using the coating solution till 3.0% weight gain is achieved.

Example 2: Pidotimod composition
Table 2
S.No Ingredients Qty/Tablet (%w/w)
Intragranular
1. Pidotimod 70.61
2. Micro Crystalline Cellulose 10.5
3. Cross Carmellose Sodium 0.7
4. Maize Starch 1.6
Binder
5. Hydroxy Propyl cellulose 2.9
6. IPA: Water (80:20) q.s.
Extra Granular
7. Cross Carmellose Sodium 7.5
8. Low Substituted Hydroxy Propyl Cellulose 1.9
9. Colloidal Silicone Dioxide 0.30
10. Magnesium Stearate 0.50
Coating
11. Hydroxypropyl Methylcellulose 1.456
12. Diethyl Phthalate 0.349
13. Ethyl Cellulose 0.262
14. Talc 0.116
15. Titanium Dioxide 0.728
16. Isopropyl Alcohol q.s.
17. Dichloromethane q.s.
Total 100

Process:
(a) All Intragranular ingredients were sifted through sieve and loaded into rapid mixer granulator (RMG);
(b) binder solution was prepared by adding Hydroxypropyl cellulose to isopropyl alcohol (IPA), water mixture under stirring and material from step (a) was granulated by using this solution;
(c) granulated material of step (b) was loaded into fluidized bed dryer (FBD) and dried at 55°C till loss on drying (LOD) obtained not more than 1.5%;
(d) dried granular material of step (c) was passed through sieve and retained material was milled using multi mill;
(e) all extragranular material except magnesium Stearate were passed through sieve and blended with dried material;
(f) magnesium Stearate was passed through sieve, added to step (e) blend;
(g) above blend was compressed to obtain tablets;
(h) coating solution was prepared by the addition of coating material (Insta Moistshield) to IPA under stirring followed by dichloromethane; and
(i) compressed tablets of step (g) were coated using the coating solution till 3.0% weight gain is achieved.

Stability data:

Table 3
S.No. Test Initial Result Accelerated
(40°C/75%RH)
1 Month 3 Month 6 Month
1 Assay (%) 100 101.5 102.3 103.7
2 Dissolution (45min); (%) 97 101 94 92.0
3 Water content by KF; (%) 0.94 1.46 1.95 1.77

Table 4
S.No. Test Initial Result Long term (30°/65% RH)
3 Month 6 Month
1 Assay (%) 100 101.5 102.2
2 Dissolution (45min); (%) 97 98.0 96.0
3 Water content by KF (%) 0.94 1.54 1.47

,CLAIMS:1. A process for the preparation of pharmaceutical composition comprising a) 60-80% pidotimod or pharmaceutically acceptable salt thereof; b) 1-3% maize starch; c) 1-6% binder; d) one or more coating and one or more pharmaceutically acceptable excipients.

2. The process according to claim 1, wherein the binder comprises hydroxy propyl cellulose.

3. The process according to claim 1, wherein the process comprises wet granulation of material and suitable coating over finished product.

4. A process of preparing solid pharmaceutical composition comprising steps of: a) mixing of pidotimod or pharmaceutically acceptable salt thereof with maize starch and optionally with one or more pharmaceutically acceptable excipients;
b) mixing of hydroxy propyl cellulose in to suitable solvent;
c) granulation of material obtained in step (a) with binder solution obtained in step (b);
d) drying, sifting of granulated material obtained in step (c);
e) mixing of material obtained in step (d) with suitable extragranular material and compression to get solid dosage form;
f) application of coating layer over dosage form obtained in step (e).

5. The process according to claim 4, wherein the binder is present in an amount ranges from about 1.0% w/w to about 6 % w/w of the composition.

6. The process according to claim 4, wherein the suitable solvent is combination of isopropyl alcohol and water.

7. The process according to claim 4, wherein the solid dosage form is preferably tablet dosage form.

8. The process according to claim 1 or 4, wherein the wherein coating material comprises ethylcellulose.

9. The process according to claim 1 or 4, wherein the wherein the composition provides immediate release of pidotimod from the dosage from.

10. A process of preparing solid pharmaceutical composition comprising steps of: a) mixing of pidotimod or pharmaceutically acceptable salt thereof with 1-3% maize starch and optionally with one or more pharmaceutically acceptable excipients;
b) mixing of 1-6% hydroxy propyl cellulose in to suitable solvent;
c) granulation of material obtained in step (a) with binder solution obtained in step (b);
d) drying, sifting of granulated material obtained in step (c);
e) mixing of material obtained in step (d) with suitable extragranular material;
f) lubrication of material obtained in step (e) and compression to get tablet dosage form;
g) application of coating layer over tablet obtained in step (f).