DESC:FIELD OF THE INVENTION
The present invention relates to the combination composition of Simethicone and Phloroglucinol Dihydrate and processes thereof.

BACKGROUND OF THE INVENTION
Simethicone is chemically known as poly(dimethyl siloxane), silicon dioxide. It is grey translucent viscous liquid, insoluble in water. The molecular weight of Simethicone is 238.6 with the following structural formula:

Simethicone is an anti-foaming agent. It relieves symptoms of excess gas in gastro- intestinal tract. [It acts as anti-flatulent].

Phloroglucinol is chemically Benzene–1,3,5-triol. It acts as an antispasmodic. The molecular weight of Phloroglucinol is 126.11 with the following structure.

Currently, Simethicone and Phloroglucinol capsules are available under the brand name of Meteoxane® Capsules in France for treatment of intestinal functional manifestations, notably with meteorism and diarrhea. Two capsules are taken three times a day before meals or at the moment of pain.

Due to the viscous nature of Simethicone, there were always difficulties in achieving sufficient flowability and in turn uniform distribution while processing into the dosage forms. Typically, to incorporate Simethicone into a solid formulation, it must first be adsorbed onto a suitable carrier or substrate. There have been several inventions related to this problem.

US4906478 relates to improving the flow properties of Simethicone by intermixing liquid Simethicone with calcium silicate. The obtained mixture can be added to conventional unit dosage forms.

US7691409 discloses compressed solid oral dosage form of Simethicone wherein Simethicone is adsorbed on adsorbents such as silicified microcrystalline cellulose and magnesium metasilicate to produce free flowing powder which processed into compressed tablets.

US6103260 discloses oral solid dosage formulation of Simethicone with tri-basic calcium phosphate or dibasic calcium phosphate wherein the admixture is uniform granular composition. The obtained granules can be compressed into solid oral dosage form.

WO2008056200 discloses an oral pharmaceutical composition that includes Simethicone adsorbed on the calcium silicate and microcrystalline cellulose. Oral pharmaceutical composition may further include one or more additional active agents.

While the above prior arts relate to Simethicone composition suitable for processing alone or in combination with drugs other than Phloroglucinol. There is no prior art which discloses stable composition of Simethicone and Phloroglucinol in the form of solid oral dosage form. Hence, there is a need for an improved composition for solid oral administration and a method for the preparation of combination composition of Simethicone and Phloroglucinol. The composition intended should be stable with improved physicochemical parameters.

The inventors of present invention developed Simethicone and Phloroglucinol capsules by dry mixing colloidal silicon dioxide, microcrystalline cellulose and di basic calcium phosphate in rapid mixer granulator followed by granulation with liquid Simethicone the obtained granules were subjected to drying and sizing followed by pre-lubricating with Phloroglucinol Dihydrate, colloidal silicon dioxide and microcrystalline cellulose, followed by lubrication with Talc and Magnesium Stearate and then filing into capsules.

Inventors have encountered difficulties such as sticking on tamping pins while filling lubricated blend into the capsules and weight variation were also observed.

Further trials were taken by changing the diluents and optimizing process parameters. Still the above difficulties existed.

To overcome above difficulties inventors have opted for the readily available powder form of Simethicone form RioCare India Pvt Ltd, which again had the same issues of sticking on tamping pins and weight variations while filling into the capsules.

By considering the difficulties of the sticking and weight variation, the inventors of the present invention have finally tried and conducted rigorous experiments for the pellet approach to produce a combination composition of Simethicone and Phloroglucinol. Surprisingly, inventors could be able to fix all the above shortcomings and that there was no sticking on tamping pins or weight variation observed, also the uniform and complete drug release obtained.

OBJECTIVE OF THE INVENTION
The main objective of the present invention is to provide a combination composition of Simethicone and Phloroglucinol Dihydrate and the process thereof. More particularly, a pellet composition of Simethicone and Phloroglucinol Dihydrate was formulated to be filled in the capsules. The composition of the present invention is stable with improved physicochemical characteristics.

SUMMARY OF THE INVENTION
The present invention provides a combination composition of Simethicone and Phloroglucinol Dihydrate.

In one aspect, the present invention provides combination composition in the form of pellets of Simethicone and pellets of Phloroglucinol Dihydrate filled in the capsules.

In another aspect, the pellet composition of present invention further comprises, diluents, binders, glidant, pH modifier and lubricants.

In yet another aspect, the pellets of Simethicone comprises:
Simethicone (Powder)
Maize Starch from about 5 % to about 20%
Microcrystalline cellulose from about 20% to about 60%
Hydroxypropyl Cellulose from about 0.1% to about 10%
Colloidal Silicon Dioxide from about 0.1% to about 20%
Talc from about 0.2% to about 5%

In yet another aspect, the pellets of Phloroglucinol comprises:
Phloroglucinol Dihydrate
Maize Starch from about 5 % to about 20%
Microcrystalline cellulose from about 20% to about 60%
Hydroxypropyl Cellulose from about 0.1% to about 10%
Talc from about 0.2% to about 5%
In yet another aspect, the pellets of composition comprises:
Simethicone from about 20% to about 60%,
Phloroglucinol from about 15% to about 60%,
Maize Starch from about 0% to about 40%,
Dibasic Calcium Phosphate from about 0% to about 40% by weight,
Microcrystalline cellulose from about 10% to about 70%,
Hydroxypropyl Cellulose from about 1% to about 30%,
Colloidal Silicon Dioxide from about 0.2% to about 15%,
Citric acid from 0.1% to about 20%
Talc from about 0.2% to about 4%

In yet another aspect, the pellets of Simethicone and pellets of Phloroglucinol filled into the capsules.

In yet another aspect, the pellets of Simethicone and pellets of Phloroglucinol mixed together and filled into the capsules.

In one of the aspects, the pellets of Simethicone and/or pellets of Phloroglucinol prepared by granulating in the Rapid Mixer Granulator with diluents, binder and optionally glidant then extrusion & spherization to obtain plurality of substantially spherical pellets.

DETAILED DESCRIPTION OF THE INVENTION
The present invention is directed to combination composition of Simethicone and Phloroglucinol Dihydrate, more specifically pellet composition of Simethicone and Phloroglucinol Dihydrate filled in capsule.

Simethicone is chemically known as poly (dimethyl siloxane), silicon dioxide. It contains 4-7% silicon dioxide and 90.5-99% polydimethyl siloxane. Simethicone is grey, translucent viscous liquid insoluble in water. Simethicone is used for symptomatic treatment of flatulence, gastric bloating and postoperative gas pains. It is combined with other medications such as antacids, antispasmodics or digestive enzymes. Simethicone powder for the current invention was obtained from RioCare India Pvt. Ltd.

Phloroglucinol is chemically Benzene–1,3,5-triol. As referred herein, the “Phloroglucinol” can be crystalline, amorphous, mixture of crystalline and amorphous, solvate or hydrate or pharmaceutically acceptable salt. Phloroglucinol is a spasmolytic agent to treat colic, as well as spastic pain of digestive and biliary tracts.

Currently, Simethicone and Phloroglucinol Dihydrate capsules are available under the brand name of Meteoxane Capsules in the France for the treatment of intestinal functional manifestations notably with meteorism and diarrhea.

The term “pellet” includes multiple-unit dosage form, which is believed to have many therapeutic advantages such as effectiveness and safety, over single-unit dosage forms.

As used in the specification and the accompanying claims, the indefinite articles “a” and “an” and the definite article “the” include plural as well as singular referents, unless the context clearly dictates otherwise.

The term “about” or “approximately” means an acceptable error for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined. In certain embodiments, the term “about” or “approximately” means within 1, 2, 3, or 4 standard deviations. In certain embodiments, the term “about” or “approximately” means within 30%, 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%,0.2%, 0.5%, 0.1%, or 0.05% of a given value or range.

In one aspect, the present invention provides combination composition in the form of pellets of Simethicone and pellets of Phloroglucinol Dihydrate filled in the capsules.

In another aspect, the pellet composition of present invention further comprises pharmaceutically acceptable excipients such as diluents, binders, lubricants, pH modifier and optionally glidant.

An “excipient,” as used herein, has its normal meaning in the art and is any ingredient of an oral dosage form that is not an active ingredient (drug) itself. Excipients are well known in the art, and the present system is not limited in these respects.

Diluents, e.g., fillers, employable in such formulations may include for example and without limitation, dicalcium phosphate (dibasic calcium phosphate), calcium diphosphate, calcium carbonate, calcium sulfate, lactose, cellulose, kaolin, sodium chloride, starches, maize starch powdered sugar, colloidal silicon dioxide, titanium oxide, alumina, talc, colloidal silica, microcrystalline cellulose, Mannitol, silicified micro crystalline cellulose and combinations thereof.

Binder materials employable in such formulations may include for example and without limitation, starches (including corn starch and pregelatinized starch), gelatin, sugars (including sucrose, glucose, dextrose and lactose), polyethylene glycol, povidone, waxes, and natural and synthetic gums, e.g., acacia sodium alginate, polyvinylpyrrolidone, cellulosic polymers (e.g., hydroxypropyl cellulose, hydroxypropyl methylcellulose, methyl cellulose, hydroxyethyl cellulose, carboxymethylcellulose, colloidal silicon dioxide NF/EP (e.g., Cab-O-Sil™ M5P), Silicified Microcrystalline Cellulose (SMCC), e.g., Silicified microcrystalline cellulose NF/EP (e.g., Prosolv™ SMCC 90), and silicon dioxide, mixtures thereof, and the like), veegum, and combinations thereof.

Glidants employable in such formulation may include for example talc, starches (e.g., cornstarch), celluloses, silicon dioxide, sodium lauryl sulfate, colloidal silica dioxide, and metallic stearates among others.

Useful lubricants employable in such formulations may include for example canola oil, glyceryl palmitostearate, hydrogenated vegetable oil (type I), magnesium oxide, magnesium stearate, mineral oil, poloxamer, polyethylene glycol, sodium lauryl sulfate, sodium stearate fumarate, stearic acid, talc and, zinc stearate, glyceryl behapate, magnesium lauryl sulfate, boric acid, sodium benzoate, sodium acetate, sodium benzoate/sodium acetate (in combination), DL leucine, calcium stearate, sodium stearyl fumarate, mixtures thereof, and the like.

pH modifier employable in such formulation may include for example (S)-lactic acid, tartaric acid, citric acid, sodium carbonate, sodium citrate mixtures thereof, and the like.

The pellets described herein may be prepared by conventional techniques using commonly available equipment known to persons skilled in the art. The process comprises involving Granulation, Extrusion and Spheronization.

The Granulation process involves Rapid Mixer Granulator, Planetary Mixer, Mass Mixer or Fluid bed granulator.

The pellets of Simethicone and/or pellets of Phloroglucinol prepared by granulating in the Rapid Mixer Granulator with diluents, binder, pH modifier and optionally glidant then extrusion & spheronization to obtain plurality of substantially spherical pellets.
In one aspect, the pellets of Simethicone were lubricated and filled into hard gelatin capsule of size 0 followed by lubricating pellets of Phloroglucinol and filling into hard gelatin capsule of size 0.
In yet another aspect, the obtained pellets of Simethicone and pellets of Phloroglucinol were mixed together lubricated and filled into the hard gelatin capsule of size 0.

In one embodiment, the present invention provides capsules filled with pellets of Simethicone and pellets of Phloroglucinol dihydrate comprising;
from about 10% to about 80% by weight of Simethicone and
from about 5% to about 90% by weight of Phloroglucinol dihydrate.

In another embodiment, pellets of Simethicone and Phloroglucinol dihydrate comprising:
Simethicone from about 15% to about 65% by weight,
Diluents from about 1% to about 50% by weight,
Binders from about 0.1% to about 20% by weight,
Glidants from about 0.1% to about 20% by weight and
Lubricants from about 0.1% to about 5% by weight.

In yet another embodiment, the present invention provides capsules filed with pellets of
Phloroglucinol from about 10% to about 75% by weight,
Diluents from about 1% to about 50% by weight,
Binders from about 0.1% to about 20% by weight and
Lubricants from about 0.1% to about 5% by weight.
In yet another embodiment, the present invention provides capsules filed with
pellets of Simethicone comprising:
Simethicone from about 15% to about 65% by weight,
Diluents from about 1% to about 50% by weight,
Binders from about 0.1% to about 20% by weight
Glidants from about 0.1% to about 20% by weight and
Lubricants from about 0.1% to about 5% by weight; and
Pellets of Phloroglucinol dihydrate comprising:
Phloroglucinol from about 10% to about 75% by weight,
Diluents from about 1% to about 50% by weight,
Binders from about 0.1% to about 20% by weight and
Lubricants from about 0.1% to about 5% by weight.

In yet another embodiment, the present invention provides capsules filed with
pellets of Simethicone comprising:
Simethicone from about 15% to about 65% by weight,
Diluents from about 1% to about 50% by weight,
Binders from about 0.1% to about 20% by weight
Glidants from about 0.1% to about 20% by weight and
Lubricants from about 0.1% to about 5% by weight; and
Pellets of Phloroglucinol dihydrate comprising:
Phloroglucinol from about 10% to about 75% by weight,
Diluents from about 1% to about 50% by weight,
Binders from about 0.1% to about 20% by weight,
pH modifiers from about 0.1% to about 20% by weight, and
Lubricants from about 0.1% to about 5% by weight.

In a more preferred embodiment, the present invention provides capsules filed
with pellets of Simethicone comprising:
Simethicone from about 20% to about 60% by weight,
Maize Starch from about 0% to about 20% by weight,
Microcrystalline Cellulose from about 2% to about 55% by weight,
Hydroxypropyl Cellulose from about 0.5% to about 15% by weight,
Colloidal Silicon Dioxide from about 0.5% to about 15% by weight,
Talc from about 0.2% to about 3% by weight, and
pellets of Phloroglucinol Dihydrate comprising:
Phloroglucinol from about 15% to about 60% by weight,
Maize Starch from about 0% to about 20% by weight,
Microcrystalline cellulose from about 2% to about 55% by weight,
Hydroxypropyl Cellulose from about 0.5% to about 15% by weight,
Talc from about 0.2% to about 3% by weight.

In a more preferred embodiment, the present invention provides capsules filed
with pellets of Simethicone comprising:
Simethicone from about 20% to about 60% by weight,
Maize Starch from about 0% to about 20% by weight,
Dibasic Calcium Phosphate from about 0% to about 20% by weight,
Microcrystalline Cellulose from about 2% to about 55% by weight,
Hydroxypropyl Cellulose from about 0.5% to about 15% by weight,
Colloidal Silicon Dioxide from about 0.5% to about 15% by weight,
Talc from about 0.2% to about 3% by weight, and
pellets of Phloroglucinol Dihydrate comprising:
Phloroglucinol from about 15% to about 60% by weight,
Maize Starch from about 0% to about 20% by weight,
Microcrystalline cellulose from about 2% to about 55% by weight,
Hydroxypropyl Cellulose from about 0.5% to about 15% by weight,
Talc from about 0.2% to about 3% by weight.

In another more preferred embodiment, pellets of Simethicone comprising:
Simethicone from about 20% to about 60% by weight,
Maize Starch from about 0% to about 20% by weight,
Microcrystalline cellulose from about 2% to about 55% by weight,
Hydroxypropyl Cellulose from about 0.5% to about 15% by weight,
Colloidal Silicon Dioxide from about 0.5% to about 15% by weight,
Talc from about 0.2% to about 3% by weight.

In another more preferred embodiment, pellets of Simethicone comprising:
Simethicone from about 20% to about 60% by weight,
Maize Starch from about 0% to about 20% by weight,
Dibasic Calcium Phosphate from about 0% to about 20% by weight,
Microcrystalline cellulose from about 2% to about 55% by weight,
Hydroxypropyl Cellulose from about 0.5% to about 15% by weight,
Colloidal Silicon Dioxide from about 0.5% to about 15% by weight,
Talc from about 0.2% to about 3% by weight.

In another more preferred embodiment, pellets of Phloroglucinol Dihydrate
comprising:
Phloroglucinol from about 15% to about 60% by weight,
Maize Starch from about 0% to about 20% by weight,
Microcrystalline cellulose from about 2% to about 55% by weight,
Hydroxypropyl Cellulose from about 0.5% to about 15% by weight,
Talc from about 0.2% to about 3% by weight.

In a more preferred embodiment, the present invention provides composition comprising:
Simethicone from about 20% to about 60% by weight,
Phloroglucinol from about 15% to about 60% by weight,
Maize Starch from about 0% to about 40% by weight,
Dibasic Calcium Phosphate from about 0% to about 40% by weight,
Microcrystalline cellulose from about 10% to about 70% by weight,
Hydroxypropyl Cellulose from about 1% to about 30% by weight,
Colloidal Silicon Dioxide from about 0.2% to about 15% by weight,
Citric acid from 0.1% to about 20% by weight and
Talc from about 0.2% to about 4% by weight.

In one embodiment, the present invention provides a pharmaceutical composition in the form of pellets of Simethicone and pellets of Phloroglucinol Dihydrate filled in the capsules.

In one embodiment, the present invention provides combination composition in the form of pellets of Simethicone and powder blend of Phloroglucinol Dihydrate filled in the capsules.

In another embodiment, the present invention provides combination composition in the form of processed Simethicone powder and powder blend of Phloroglucinol Dihydrate filled in the capsules.

In another embodiment, the present invention provides combination composition in the form of pellets of Simethicone and tablet of Phloroglucinol Dihydrate filled in the capsules.
In another embodiment, the present invention provides combination composition in the form of processed Simethicone powder and tablet of Phloroglucinol Dihydrate filled in the capsules.

The following examples are intended to be illustrative and non-limiting:
Example 1:
Table 1
S.NO Ingredients Quantity /capsule)
For 125 mg/80 mg
Dry Mix (Simethicone Pellet)
1 Simethicone (Powder) 125.00
2 Maize Starch 25.00
3 Microcrystalline Cellulose (Ceolus 101) 180.00
4 Colloidal Silicon Dioxide 3.00
Binder
4 Hydroxypropyl Cellulose (Klucel LF) 6.00
5 Purified Water Qs
Lubrication
6 Talc 1.00
Average Weight of Simethicone Pellet 340.00
Dry Mix (Phloroglucinol Pellet)
7 Phloroglucinol Dihydrate 80.00
8 Maize Starch 9.00
9 Microcrystalline Cellulose 15.00
10 Hydroxypropyl Cellulose 3.00
Binder -2
10 Hydroxypropyl Cellulose (Klucel LF) 2.00
11 Purified Water Qs
Lubrication
12 Talc 1.00
Average Weight of Phloroglucinol Pellet 110.00
Total Weight of Pellet 450.00
Size “0” capsule size

Manufacturing Process:
1. Simethicone Pellet:
Co-sifted Simethicone, Microcrystalline cellulose, maize starch and colloidal silicon dioxide were dry mixed for 15 min in rapid mixer granulator, the mixture was granulated with binder solution of Hydroxypropyl cellulose in water. Wet mass was extruded with extruder using 1.00 mm colonical screen at 80 rpm, extrudates were spheronized with spherodizer to obtain spheres. Spheres were dried, sized using sieve #12 and #24 and lubricated with talc for 5 min in blender at slow speed.
2. Phloroglucinol Dihydrate Pellet:
Co-sifted Phloroglucinol, Microcrystalline cellulose, maize starch and hydroxypropyl cellulose were dry mixed for 15 min in rapid mixer granulator, the mixture was granulated with binder solution of Hydroxypropyl cellulose in water. Wet mass was extruded with extruder using 1.00 mm colonical screen at 80 rpm, extrudates were spheronized with spherodizer to obtain spheres. Spheres were dried, sized using sieve #12 and #24 and lubricated with talc for 5 minutes in blender at slow speed.
3. Capsule Filing:
Lubricated pellets of Simethicone and lubricated pellets of Phloroglucinol were filled in capsules.
Example 2:
Table 2:

S.NO Ingredients Quantity (mg/capsule)
Dry Mix (Phloroglucinol Dihydrate Pellet)
1 Phloroglucinol Dihydrate 80.00
2 Maize Starch 10.00
3 Microcrystalline Cellulose (Ceolus 101) 16.00
Binder -1
4 Hydroxypropyl Cellulose (Klucel LF) 3.00
5 Purified Water qs
Lubrication
6 Talc 1.00
Dry Mix (Simethicone Pellet)
7 Simethicone (Powder) 125.00
8 Maize Starch 25.00
9 Microcrystalline Cellulose 177.00
Binder -2
10 Hydroxypropyl Cellulose (Klucel LF) 6.00
11 Purified Water qs
Lubrication
12 Talc 5.00
Total Weight of Pellet 455.00
Size “0” capsule size

Process:
1. Phloroglucinol Dihydrate Pellet:
Co-sifted Phloroglucinol, Microcrystalline cellulose and maize starch were dry mixed for 15 min in rapid mixer granulator; the mixture was granulated with binder solution of Hydroxypropyl cellulose in water. Wet mass was extruded and spheronized with spherodizer to obtain spheres. Spheres were dried, sized using sieve #12 and #24 and lubricated with talc for 5 minutes in blender at slow speed.

2. Simethicone Pellet:
Co-sifted Simethicone, Microcrystalline cellulose and maize starch were dry mixed in rapid mixer granulator, the mixture was granulated with binder solution of Hydroxypropyl cellulose in water. Wet mass was extruded and spheronized with to obtain spheres. Spheres were dried, sized using sieve #12 and #24 and lubricated with talc for 5 minutes in blender at slow speed.
3. Capsule Filing:
Lubricated pellets of Simethicone and lubricated pellets of Phloroglucinol were filled in capsules.
Example 3:

Table 3:

S.NO. Ingredients Quantity (mg/capsule)
Dry Mix (Simethicone Pellet)
1 Simethicone (Powder) 125.00
2 Maize Starch 25.00
3 Microcrystalline Cellulose (Ceolus 101) 177.00
Binder -1
4 Hydroxypropyl Cellulose (Klucel LF) 6.00
5 Purified Water qs
Lubrication
6 Talc 2.00
Dry Mix (Phloroglucinol Dihydrate Pellet)
7 Phloroglucinol Dihydrate 80.00
8 Maize Starch 10.00
9 Microcrystalline Cellulose 16.00
Binder -2
10 Hydroxypropyl Cellulose (Klucel LF) 3.00
11 Purified Water Q.S.
Lubrication
12 Talc 1.00
Total Weight of Pellet 445.00
Size “0” capsule size

1. Simethicone Pellet:
Co-sifted Simethicone, Microcrystalline cellulose and maize starch were dry mixed in rapid mixer granulator, the mixture was granulated with binder solution of Hydroxypropyl cellulose in water. Wet mass was extruded and spheronized with to obtain spheres. Spheres were dried, sized using sieve #12 and #24 and lubricated with talc for 5min in blender at slow speed.

2. Phloroglucinol Dihydrate Pellet:
Co-sifted Phloroglucinol, Microcrystalline cellulose and maize starch were dry mixed for 15 min in rapid mixer granulator; the mixture was granulated with binder solution of Hydroxypropyl cellulose in water. Wet mass was extruded and spheronized with spherodizer to obtain spheres. Spheres were dried, sized using sieve #12 and #24 and lubricated with talc for 5min in blender at slow speed.
3. Capsule Filing:
Lubricated pellets of Simethicone and lubricated pellets of Phloroglucinol were filled in capsules.

Example 4:
Table 4:
S.NO Ingredients Quantity /capsule)
For 125 mg/80 mg
Dry Mix (Simethicone Pellet)
1 Simethicone (50% Powder) 125.000
2 Microcrystalline cellulose (Ceolus PH 101) 177.000
3 Dibasic Calcium Phosphate Dihydrate 10.000
4 Colloidal silicon dioxide (Aerosil 200 Pharma) 3.000
Binder
5 Hydroxypropyl Cellulose (Klucel LF) 4.00
6 Purified Water Q.S.
Lubrication
7 Talc 1.00
Average Weight of Simethicone Pellet 320.00
Dry Mix (Phloroglucinol Pellet)
8 Phloroglucinol Dihydrate 80.00
9 Microcrystalline cellulose (Ceolus PH 101) 16.00
Binder -2
10 Hydroxypropyl Cellulose (Klucel LF) 3.00
11 Citric acid monohydrate 20.00
12 Purified Water Q.S.
Lubrication
13 Talc 1.00
Average Weight of Phloroglucinol Pellet 120.00
Total Weight of Pellet 440.00
Size “0” capsule size

1. Simethicone Pellet:
Co-sifted Simethicone, Microcrystalline cellulose, dibasic calcium phosphate dihydrate and Colloidal silicon dioxide were dry mixed in rapid mixer granulator, the mixture was granulated with binder solution of Hydroxypropyl cellulose in water. Wet mass was extruded and spheronized with to obtain spheres. Spheres were dried, sized using sieve #14 and #30 and lubricated with talc for 5min in blender at slow speed.

2. Phloroglucinol Dihydrate Pellet:
Co-sifted Phloroglucinol, Microcrystalline cellulose and maize starch were dry mixed for 15 min in rapid mixer granulator; the mixture was granulated with binder solution of Hydroxypropyl cellulose and Citric acid monohydrate in water. Wet mass was extruded and spheronized with spherodizer to obtain spheres. Spheres were dried, sized using sieve #14 and #30 and lubricated with talc for 5 min in blender at slow speed.
3. Capsule Filing:
Lubricated pellets of Simethicone and lubricated pellets of Phloroglucinol were filled in capsules.

Comparison of in-vitro dissolution profile:
The pellets of Simethicone and Phloroglucinol Dihydrate in capsule of Example-1, 2, 3 and 4 of the present invention and reference product (Meteoxane®) were subjected to dissolution studies in 900 ml of 0.1N HCl in 1.0% SLS at 37°C ± 0.5°C using USP Apparatus-Type I (Basket).

Table 5: The comparative dissolution data
Time (min.) Drug released (Percent w/w)
Meteoxane® Example 1 Example 2 Example 3 Example 4
15 58.79 68.64 63.3 70.28 43.4
20 72.70 78.90 72.6 79.63 49.2
30 87.01 90.29 84.5 91.11 58.8
45 95.97 98.00 93.5 98.18 69.0
60 99.69 99.92 96.5 99.41 76.7
Recovery 102.73 100.00 97.1 99.47 81.3

Based on the above results, the release profile of pellets of Simethicone and Phloroglucinol Dihydrate in capsule of example 1, 2, 3 and 4 is found to be similar to the Reference product ,CLAIMS:1. A pharmaceutical composition comprising Simethicone from about 15% to about 65% by weight and Phloroglucinol from about 10% to about 75% by weight of the composition.

2. The pharmaceutical composition as claimed in claim 1, wherein the composition comprises one or more pharmaceutically acceptable excipients selected from diluents, binders, glidants, pH modifiers and lubricants.

3. The pharmaceutical composition as claimed in claim 1, wherein the composition is in the form of pellets of Simethicone and pellets of Phloroglucinol filled into the capsules.

4. The pharmaceutical composition as claimed in claim 2, wherein the composition comprises:
pellets of Simethicone comprising:
Simethicone from about 15% to about 65% by weight,
diluents from about 1% to about 50% by weight,
binders from about 0.1% to about 20% by weight,
glidants from about 0.1% to about 20% by weight and
lubricants from about 0.1% to about 5% by weight;
and pellets of Phloroglucinol comprising:
Phloroglucinol from about 10% to about 75% by weight,
diluents from about 1% to about 50% by weight,
binders from about 0.1% to about 20% by weight,
pH modifiers from about 0.1% to about 20% by weight and
lubricants from about 0.1% to about 5% by weight.

5. A pharmaceutical composition comprising:
Simethicone from about 20% to about 60% by weight,
Phloroglucinol from about 15% to about 60% by weight,
Maize Starch from about 0% to about 40% by weight,
Dibasic Calcium Phosphate from about 0% to about 40% by weight,
Microcrystalline cellulose from about 10% to about 70% by weight,
Hydroxypropyl cellulose from about 1% to about 30% by weight,
Colloidal silicon dioxide from about 0.2% to about 15% by weight,
Citric acid from about 0.1% to about 20% by weight and
Talc from about 0.2% to about 4% by weight.

6. The pharmaceutical composition as claimed in claims 1-5, wherein the composition is prepared by the process comprising of:
mixing Simethicone or Phloroglucinol with one or more pharmaceutically acceptable excipients;
extruding and spheronizing obtained mass in above step to form plurality of pellets;
drying and lubricating the pellets;
filling the pellets into capsule.