DESC:BACKGROUND OF THE INVENTION
Diabetes mellitus is a common disorder more prevalent in developed countries. In the United States diabetes mellitus affects approximately 7.5 million people. It is characterized by its clinical manifestations, namely the non-insulin-dependent or maturity onset form, also known as Type 2 diabetes and the insulin-dependent or juvenile onset form, also known as Type 1 diabetes. Type 2 diabetes is a disease characterized by high-circulating blood glucose, insulin and corticosteroid levels.
Metformin is the member of the biguanide class of an oral antihyperglycemics and available in various salt forms, e.g. hydrochloride. Metformin is used in the management of type 2 diabetes mellitus. It is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose.

Leucine is a branched-chain alpha amino acid since it possesses an aliphatic side-chain that is non-linear. It is hydrophobic in nature. It is an essential type of amino acid and is not synthesized in human body, and therefore it must be ingested. Chemically, leucine is 2-Amino-4-methylpentanoic acid, with following chemical structure:

Leucine along with metformin or pharmaceutically acceptable salt thereof synergistically increases insulin sensitivity thus enhances therapeutic efficacy of metformin or pharmaceutically acceptable salt thereof and also dose required to achieve desired therapeutic effect of metformin or pharmaceutically acceptable salt thereof is reduced. Reduction in dose of Metformin or pharmaceutically acceptable salt thereof will lead to reduced long term use side effect of Metformin or pharmaceutically acceptable salt thereof.

U.S. Patent No. 9,072,692 discloses compositions comprising leucine, its metabolites with metformin and methods useful for treating diabetes, inducing an increase in fatty acid oxidation or mitochondrial biogenesis, reducing weight gain, inducing weight loss.
U.S. Patent No. 8,623,924 discloses compositions comprising leucine and/or leucine metabolites and methods useful for inducing an increase in fatty acid oxidation or mitochondrial biogenesis, reducing weight gain, inducing weight loss.
U.S. Patent No. 8,617,886 discloses compositions comprising leucine and/or leucine metabolites, wherein use of metformin is also suggested.
U.S. Patent No. 6,340,475 discloses a controlled-release oral drug dosage formulation designed for gastric retention and controlled delivery of metformin into the gastric cavity.
Extended-release formulations of metformin are disclosed in several other U.S. Patent No.s 6,635,280; 6,866,866; 6,475,521 and 6,660,300.
The use of metformin hydrochloride in sustained release tablets dosage form for the treatment of diabetes is known since years, but the daily dose of metformin is considerably very high.
Metformin Hydrochloride is water soluble drug. The daily recommended starting dose of metformin is very high, 500 mg to 850 mg for children, adults and adolescents which are administered several times in a day depending on the diabetic condition of the individual. The maximum recommended dose of metformin hydrochloride is 3 grams daily, taken in three divided doses.
Metformin Hydrochloride provides even more effective treatment of type II diabetes. Although metformin is effective at lowering blood glucose levels, its use is associated with gastrointestinal (GI) adverse effects, particularly diarrhea and nausea. These adverse effects may limit the tolerated dose of metformin and cause patients to discontinue the therapy.
There are some side effects of long term use of metformin which leads to different side effects like Malaise, which is a general feeling of discomfort, illness, or unease whose exact cause is difficult to identify; digestive effects like gastrointestinal disturbances affecting the stomach and intestines are common effects of metformin; Vitamin B12 malabsorption may also occur in some patients on long term metformin treatment; long-term metformin use can cause liver or kidney problems in some individuals.
There are numerous literatures available which suggest combined use of metformin and leucine for treatment of obese type 2 diabetics in that it significantly affects weight loss and related disorders, however, there still exists a need to find better options for treating diabetes which may eliminate or reduce side effects that are associated with current therapy. Metformin Hydrochloride and leucine has unpleasant tastes such as bitterness and saltiness which need to be masked for better compliance and acceptability of medication regimens or could lead to medication errors. Therefore it is necessary to develop a taste masked composition of metformin or pharmaceutically acceptable salt thereof and leucine.
Hence taste masked composition of metformin or pharmaceutically acceptable salt thereof and leucine is developed using sugar alcohol and non-nutritive sweetener which imparts a sweet taste but does not increase blood glucose level of the patient.
To develop a composition of metformin or pharmaceutically acceptable salt thereof and leucine with sweetener as a taste masking agent which will not increase blood sugar levels is a challenging task.
Therefore there exists a dire need to develop novel taste masked composition of metformin or pharmaceutically acceptable salt thereof and leucine which will have reduced long term use side effect of metformin or pharmaceutically acceptable salt thereof.
Hence it is an object of the invention to provide a novel taste masked composition of metformin or pharmaceutically acceptable salt thereof and leucine in order to reduce long term use side effect of Metformin or pharmaceutically acceptable salt thereof.
The invention also provides process for preparing pharmaceutical compositions comprising pharmaceutically effective amounts of metformin or pharmaceutically acceptable salt thereof and leucine. The compositions of the invention are useful as anti-diabetics in the treatment of diabetes.

The inventors of the invention have surprisingly found that it is possible to formulate a taste masked composition of leucine and metformin or pharmaceutically acceptable salt thereof, which will reduce side effect of metformin or pharmaceutically acceptable salt thereof after long term use.
SUMMARY OF THE INVENTION
In one general aspect, there is provided a composition comprising combination of metformin or pharmaceutically acceptable salt thereof and leucine.
In another general aspect, there is provided an oral pharmaceutical composition comprising metformin or pharmaceutically acceptable salt thereof and leucine.
In another general aspect, there is provided an oral pharmaceutical taste masked composition comprising metformin or pharmaceutically acceptable salt thereof and leucine, wherein composition is present in the form of powder, granules, tablet, capsule, solution, suspension, powder for solution.
In another general aspect, there is provided a process of preparing an oral pharmaceutical composition in the form of powder for solution comprising:
a) metformin or pharmaceutically acceptable salt thereof;
b) leucine; and
c) one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the metformin or pharmaceutically acceptable salt thereof is present in the range of 5% w/w to 20% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the metformin or pharmaceutically acceptable salt thereof is present in the range of 5% w/w to 10% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the metformin or pharmaceutically acceptable salt thereof is present in the amount of 7.8% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the leucine is present in the range of 30% to 40% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the leucine is present in the range of 30% to 35% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the leucine is present in the amount of 34.37% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the ratio of metformin or pharmaceutically acceptable salt thereof to leucine is about 1:3 to about 1:6.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the ratio of metformin or pharmaceutically acceptable salt thereof to leucine is about 1:4 to about 1:5.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the ratio of metformin or pharmaceutically acceptable salt thereof to leucine is 1:4.4

In another general aspect, there is provided a process of preparing an oral pharmaceutical composition in the form of powder for solution comprising:
a) 250mg metformin or pharmaceutically acceptable salt thereof;
b) 1100mg leucine; and
c) one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided p process of preparing a pharmaceutical composition comprising:
a) 7.8 % w/w metformin or pharmaceutically acceptable salt thereof;
b) 34.37% w/w leucine; and
c) one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a process of preparing an oral pharmaceutical composition in the form of powder for solution comprising:
a) 250mg metformin or pharmaceutically acceptable salt thereof;
b) 1100mg leucine;
c) 500mg mannitol;
d) 1131mg sorbitol;
e) 45mg xanthan gum; and
f) one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the mannitol is present in the range of 10-20% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the mannitol is present in the amount of 15.55% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the sorbitol is present in the range of 30% w/w to 40% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the sorbitol is present in the amount of 35.34% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the ratio of mannitol to sorbitol is about 1:3 to about 1:5.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the ratio of mannitol to sorbitol is about 1:2 to about 1:3.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the xanthan gum is present in the range of 1% w/w to 2% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition in the form of powder for solution, wherein the xanthan gum is present in the amount of 1.4% w/w of the composition.

In another general aspect, there is provided a process of preparing a pharmaceutical composition in the form of powder for solution comprising:
a) about 5-20 % w/w metformin or pharmaceutically acceptable salt thereof;
b) about 34.37% w/w leucine;
c) about 15.55% w/w mannitol;
d) about 35.34% w/w sorbitol;
e) about 1.4% w/w xanthan gum and
f) one or more pharmaceutically acceptable excipients.
In another general aspect, there is provided a process for preparing an oral pharmaceutical taste masked composition comprising metformin or pharmaceutically acceptable salt thereof and leucine, wherein the process comprises steps of:
(a) mixing the metformin or pharmaceutically acceptable salt thereof with one or more pharmaceutical excipients;
(b) granulating the mixture using suitable binder solution; and
(c) drying to get granules and lubricating them.

In another general aspect, there is provided an oral pharmaceutical taste masked composition comprising metformin or pharmaceutically acceptable salt thereof and leucine, wherein composition is present in the form of powder, granules, tablet, capsule, solution, suspension, powder for solution.
In another general aspect, the pharmaceutical composition is administered by mixing contents with purified water to get solution.
In another general aspect, there is provided a process for preparing of an oral pharmaceutical taste masked composition comprising metformin or pharmaceutically acceptable salt thereof and leucine, wherein the process comprises steps of:
(a) mixing the metformin or pharmaceutically acceptable salt thereof with one or more pharmaceutical excipients;
(b) granulating the mixture using suitable binder solution;
(c) drying and milling them to get granules of desired size; and
(d) blending with taste masking agents to get the final dosage form.

In another general aspect, there is provided a method of treating type-2 diabetes mellitus in a patient which method comprising administering the pharmaceutical composition as substantially described in the invention.

DETAILED DESCRIPTION OF THE INVENTION
The term "metformin" used throughout the specification refers to not only metformin per se, but also their other pharmaceutically acceptable salt, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs and pharmaceutically acceptable prodrugs thereof.
The term "taste-masking agent" or “taste-modifying agent” is used herein to describe an agent that improves the palatability of a pharmaceutical composition by masking an undesirable taste or odor. Taste-masking agents include, but are not limited to, sweetening agents, flavoring agents, anti-bitter mask components, visc
osity-enhancers, colors, and aroma excipients (e.g., menthol, yellow-plum-lemon aroma). Examples of sweetening agents include, but are not limited to, natural and synthetic sweeteners such as sucrose, dextrose, fructose, high fructose corn syrup, maltol, invert sugar, sorbitol, saccharin, maltitol, xylitol, saccharin sodium, sucralose, aspartame, acesulfame potassium, and cyclamates. Flavoring agents include any natural or synthetic compounds known to persons having skill in the art to impart flavors including, but not limited to, grape, cherry, berry, citrus, other fruits, mint, vanilla, chocolate, bubble gum and cinnamon.
The compositions of the invention can be prepared together with at least one pharmaceutically acceptable excipient or as oral, parental, inhalation dosage forms comprising the active agent. The pharmaceutical compositions of the invention can be prepared in different dosage forms comprising tablet; capsule; enterically coated or modified-release tablets; controlled-release tablet, extended-release tablet; delayed-release tablet; slow or fast-release tablet; fast soluble tablet; effervescent tablet; effervescent granule; fast soluble powder mixture; water-soluble powder, tablet, or granule; granule; pellet; mini tablet; micro tablet; granule in capsule; pellet in capsule; mini tablet in capsule; micro tablet in capsule or dry powder mixture to prepare syrup; orodispersible tablet; film tablet or combinations thereof; or in any one of liquid forms such as syrup or suspension.
As used herein, 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. This term includes active treatment, that is, treatment directed specifically toward the improvement of a disease, pathological condition, or disorder, and also includes causal treatment, that is, treatment directed toward removal of the cause of the associated disease, pathological condition, or disorder.
Pharmaceutical excipients that can be used in the pharmaceutical composition of the invention can be selected from a group comprising one or more binding agents (binders), disintegrants, lubricants, one or more diluents, glidants, wetting agents, coating agents, anti-adhesive agents, swelling agent, viscosity enhancing agents, filling agents, drying agents, rate controlling polymer agent, surfactants, cosolvents, acidifier, alkaliser, stabilizing agents, pH regulators, flavouring agent, sweeteners, emulgators, antifoaming agents, antioxidants, protective agents, solvents or solvent combinations, colouring agents and complexing agents or the combinations thereof.

The disintegrants that can be used in the pharmaceutical compositions of the invention can be selected from a group comprising carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, microcrystalline cellulose, methyl cellulose, chitosan, starch, sodium starch glycolate or combinations thereof.
The binders that can be used in the pharmaceutical compositions of the invention can be selected from a group comprising carboxymethyl cellulose sodium, ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminum silicate, maltodextrin, methyl cellulose, povidone, co-povidone, starch or combinations thereof.
The diluents that can be used in the pharmaceutical compositions according to the invention can be selected from a group comprising calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, microcrystalline cellulose, dextrose, fructose, lactitol, lactose, magnesium carbonate, magnesium oxide, maltitol, maltodextrin, maltose, mannitol, simethicone, sorbitol, starch and starch derivatives, sodium chloride, sucrose, talc, xylitol or the combinations thereof.
The lubricants that can be used in the pharmaceutical compositions of the invention can be selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, sodium benzoate, potassium benzoate, sodium lauryl sulphate, talc, stearic acid, zinc stearate or combinations thereof.
The glidants that can be used in the pharmaceutical compositions according to the invention can be selected from but not limited to colloidal silicon dioxide, calcium silicate, magnesium silicate, silicon hydrogel, magnesium trisilicate, cornstarch, talc and the like or combinations thereof.
The pharmaceutical compositions of the invention are prepared by wet or dry processing methods. In general aspect of the invention the pharmaceutical compositions are prepared by wet processing methods. In a class of this aspect the pharmaceutical compositions are prepared by wet granulation methods. With wet granulation either high-shear granulation or fluid-bed granulation may be used. In this aspect fluid-bed granulation is employed.

The pharmaceutical compositions obtained by the dry or wet processing methods may be compressed into tablets, encapsulated, or metered into sachets.
The pharmaceutical compositions of the invention may also contain one or more additional formulation ingredients selected from a wide variety of excipients known in the pharmaceutical formulation art. According to the desired properties of the pharmaceutical composition, any number of ingredients may be selected, alone or in combination, based upon their known uses in preparing compositions. Such ingredients include, but are not limited to, diluents, compression aids, glidants, disintegrants, lubricants, flavors, flavor enhancers, sweeteners, and preservatives.
In one embodiment, there is provided a composition comprising combination of metformin or pharmaceutically acceptable salt thereof and leucine.
In another embodiment, there is provided an oral pharmaceutical composition comprising metformin or pharmaceutically acceptable salt thereof and leucine.
In another embodiment,, there is provided an oral pharmaceutical taste masked composition comprising metformin or pharmaceutically acceptable salt thereof and leucine, wherein composition is present in the form of powder, granules, tablet, capsule, solution, suspension, powder for solution.
In another embodiment, there is provided a process of preparing an oral pharmaceutical composition in the form of powder for solution comprising:
a) metformin or pharmaceutically acceptable salt thereof;
b) leucine; and
c) one or more pharmaceutically acceptable excipients.

In another embodiment,, there is provided a pharmaceutical composition in the form of powder for solution, wherein the metformin or pharmaceutically acceptable salt thereof is present in the range of 5% w/w to 20% w/w of the composition.

In another embodiment,, there is provided a pharmaceutical composition in the form of powder for solution, wherein the metformin or pharmaceutically acceptable salt thereof is present in the range of 5% w/w to 10% w/w of the composition.

In another embodiment,, there is provided a pharmaceutical composition in the form of powder for solution, wherein the metformin or pharmaceutically acceptable salt thereof is present in the amount of 7.8% w/w of the composition.

In another embodiment, there is provided a pharmaceutical composition in the form of powder for solution, wherein the leucine is present in the range of 30% to 40% w/w of the composition.

In another embodiment, there is provided a pharmaceutical composition in the form of powder for solution, wherein the leucine is present in the range of 30% to 35% w/w of the composition.

In another embodiment, there is provided a pharmaceutical composition in the form of powder for solution, wherein the leucine is present in the amount of 34.37% w/w of the composition.

In another embodiment,, there is provided a pharmaceutical composition in the form of powder for solution, wherein the ratio of metformin or pharmaceutically acceptable salt thereof to leucine is about 1:3 to about 1:6.

In another embodiment, there is provided a pharmaceutical composition in the form of powder for solution, wherein the ratio of metformin or pharmaceutically acceptable salt thereof to leucine is about 1:4 to about 1:5.

In another embodiment, there is provided a pharmaceutical composition in the form of powder for solution, wherein the ratio of metformin or pharmaceutically acceptable salt thereof to leucine is 1:4.4

In another embodiment, there is provided a process of preparing an oral pharmaceutical composition in the form of powder for solution comprising:
a) 250mg metformin or pharmaceutically acceptable salt thereof;
b) 1100mg leucine; and
c) one or more pharmaceutically acceptable excipients.

In another embodiment, there is provided a pharmaceutical composition comprising:
a) 7.8 % w/w metformin or pharmaceutically acceptable salt thereof;
b) 34.37% w/w leucine; and
c) one or more pharmaceutically acceptable excipients.

In another embodiment, there is provided a process of preparing an oral pharmaceutical composition in the form of powder for solution comprising:
a) 250mg metformin or pharmaceutically acceptable salt thereof;
b) 1100mg leucine;
c) 500mg mannitol;
d) 1131mg sorbitol;
e) 45mg xanthan gum; and
f) one or more pharmaceutically acceptable excipients.

In another embodiment, there is provided a pharmaceutical composition in the form of powder for solution, wherein the mannitol is present in the range of 10-20% w/w of the composition.

In another embodiment, there is provided a pharmaceutical composition in the form of powder for solution, wherein the mannitol is present in the amount of 15.55% w/w of the composition.

In another embodiment, there is provided a pharmaceutical composition in the form of powder for solution, wherein the sorbitol is present in the range of 30% w/w to 40% w/w of the composition.

In another embodiment, there is provided a pharmaceutical composition in the form of powder for solution, wherein the sorbitol is present in the amount of 35.34% w/w of the composition.

In another embodiment, there is provided a pharmaceutical composition in the form of powder for solution, wherein the ratio of mannitol to sorbitol is about 1:3 to about 1:5.

In another embodiment, there is provided a pharmaceutical composition in the form of powder for solution, wherein the ratio of mannitol to sorbitol is about 1:2 to about 1:3.

In another embodiment, there is provided a pharmaceutical composition in the form of powder for solution, wherein the xanthan gum is present in the range of 1% w/w to 2% w/w of the composition.

In another embodiment, there is provided a pharmaceutical composition in the form of powder for solution, wherein the xanthan gum is present in the amount of 1.4% w/w of the composition.

In another embodiment, there is provided a process of preapring a pharmaceutical composition in the form of powder for solution comprising:
a) about 5-20 % w/w metformin or pharmaceutically acceptable salt thereof;
b) about 34.37% w/w leucine;
c) about 15.55% w/w mannitol;
d) about 35.34% w/w sorbitol;
e) about 1.4% w/w xanthan gum and
f) one or more pharmaceutically acceptable excipients.
In another embodiment, there is provided a process for preparing an oral pharmaceutical taste masked composition comprising metformin or pharmaceutically acceptable salt thereof and leucine, wherein the process comprises steps of:
(a) mixing the metformin or pharmaceutically acceptable salt thereof with one or more pharmaceutical excipients;
(b) granulating the mixture using suitable binder solution; and
(c) drying to get granules and lubricating them.
In another embodiment, there is provided an oral pharmaceutical taste masked composition comprising metformin or pharmaceutically acceptable salt thereof and leucine, wherein composition is present in the form of powder, granules, tablet, capsule, solution, suspension, powder for solution.
In another embodiment, there is provided a process for preparation of an oral pharmaceutical taste masked composition comprising metformin or pharmaceutically acceptable salt thereof and leucine, wherein the process comprises steps of:
(a) mixing the metformin or pharmaceutically acceptable salt thereof with one or more pharmaceutical excipients;
(b) granulating the mixture using suitable binder solution;
(c) drying and milling them to get granules of desired size; and
(d) blending with taste masking agents to get the final dosage form.
In another embodiment, there is provided a method of treating type-2 diabetes mellitus in a patient which method comprising administering the pharmaceutical composition as substantially described in the invention.
The 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 invention.
In accordance with the invention taste masked formulations are set out below.

EXAMPLES
Example 1: Pharmaceutical composition comprising Metformin or pharmaceutically acceptable salt thereof

Sr. No. Ingredients Quantity (mg/Sachet)
A] Intragranular
Dry Mix
1 Metformin Hydrochloride 250.00
2 Mannitol (Pearlitol 25C) 270-330
3 Maize Starch 90-110
4 Leucine 1100.00
Binder
5 Hypromellose 3CPS 10-25
6 Sodium Lauryl Sulphate 10-20
7 Purified water q. s.
B] Extragranular
8 Mannitol (Pearlitol SD 200) 175-225
9 Sorbitol (Neosorb P300DC) 1000-1250
10 Sucralose 25-35
11 Xanthan gum 75 35-55
12 Ponceau 4R supra 2-5
13 Trusil Strawberry flavour 10-16
Total 3000-3400

Manufacturing Procedure:
Metformin hydrochloride was milled through multi-mill (1 mm screen). Mannitol, maize starch and leucine were sifted through #30 mesh. Sodium lauryl sulphate was dissolved in water followed by dissolving hypromellose in same solution. The presifted materials were then loaded in rapid mixer granulator and are mixed for 10 minutes. Then the granulation was carried out using binder solution. The granules were then dried in fluidized bed dryer. The dried granules were then passed through the #30 mesh and retention was passed through 1.5 mm screen. Mannitol, sorbitol and trusil strawberry flavor were sifted through the #40 mesh and co-sifting of sucralose, xanthan gum and Ponceau 4R supra was through the #100 mesh. Then the sized granules and sifted materials were loaded in blender and mixed for about 15 minutes to get fine powder to make an oral solution.

Example 2: Pharmaceutical composition comprising Metformin or pharmaceutically acceptable salt thereof

Sr. No. Ingredients Quantity
(mg/sachet) Quantity
(%w/w)
A] Intragranular
Dry Mix
1 Metformin Hydrochloride 250 7.8
2 Mannitol (Pearlitol 25C) 300 9.3
3 Maize Starch 100 3.1
4 Leucine 1100 34.37
Binder
5 Hypromellose 3CPS 16 0.5
6 Sodium Lauryl Sulphate 13 0.4
7 Purified water q. s. q. s.
B] Extragranular
8 Mannitol (Pearlitol SD 200) 200 6.25
9 Sorbitol (Neosorb P300DC) 1131 35.34
10 Sucralose 30 0.93
11 Xanthan gum 75 45 1.4
12 Ponceau 4R supra 3 0.09
13 Trusil Strawberry flavour 12 0.38
Total 3200 100

Manufacturing Procedure: Same as mentioned above for Example-1.

,CLAIMS:1. A process of preparing an oral pharmaceutical composition in the form of powder for solution comprising:
a) metformin or pharmaceutically acceptable salt thereof;
b) leucine; and
c) one or more pharmaceutically acceptable excipients.

2. A process for preparing an oral pharmaceutical taste masked composition comprising metformin or pharmaceutically acceptable salt thereof and leucine, wherein the process comprises steps of:
(a) mixing the metformin or pharmaceutically acceptable salt thereof with leucine and one or more pharmaceutical excipients;
(b) granulating the mixture using suitable binder solution; and
(c) drying to get granules and lubricating them.

3. A process for preparing of an oral pharmaceutical taste masked composition comprising metformin or pharmaceutically acceptable salt thereof and leucine, wherein the process comprises steps of:
(a) mixing the metformin or pharmaceutically acceptable salt thereof with leucine and one or more pharmaceutical excipients;
(b) granulating the mixture using suitable binder solution;
(c) drying and milling them to get granules of desired size; and
(d) blending with taste masking agents to get the final dosage form.

4. A process of preparing an oral pharmaceutical composition according to claim 1, in the form of powder for solution comprising:
a) 7.8 % w/w metformin or pharmaceutically acceptable salt thereof;
b) 34.37% w/w leucine; and
c) one or more pharmaceutically acceptable excipients.

5. A process of preparing an oral pharmaceutical composition in the form of powder for solution comprising:
a) 250mg metformin or pharmaceutically acceptable salt thereof;
b) 1100mg leucine;
c) 500mg mannitol;
d) 1131mg sorbitol;
e) 45mg xanthan gum; and
f) one or more pharmaceutically acceptable excipients.

6. A process of preparing a pharmaceutical composition in the form of powder for solution comprising:
a) about 5-20 % w/w metformin or pharmaceutically acceptable salt thereof;
b) about 34.37% w/w leucine;
c) about 15.55% w/w mannitol;
d) about 35.34% w/w sorbitol;
e) about 1.4% w/w xanthan gum and
f) one or more pharmaceutically acceptable excipients.