WO2011154975A2

WO2011154975A2 - Pharmaceutical compositions of metformin

Info

Publication number: WO2011154975A2
Application number: PCT/IN2011/000378
Authority: WO
Inventors: Sunilendu Bhushan Roy; Sushrut Krishnaji Kulkarni; Maulik Kiritkumar Panchal
Original assignee: Cadila Healthcare Ltd
Current assignee: Zydus Lifesciences Ltd
Priority date: 2010-06-08
Filing date: 2011-06-07
Publication date: 2011-12-15
Anticipated expiration: 2012-12-08
Also published as: WO2011154975A3

Abstract

The invention relates to pharmaceutical compositions of metformin or pharmaceutically acceptable salts thereof. In particular, the invention relates to stable pharmaceutical compositions of metformin, which can be reconstituted in water prior to administration; process of manufacturing such compositions and their use in treating hyperglycemia and/or diabetes.

Description

PHARMACEUTICAL COMPOSITIONS OF METFORMIN

FIELD OF THE INVENTION

The present invention relates to pharmaceutical compositions of metformin or pharmaceutically acceptable salts thereof. In particular, the present invention relates to stable pharmaceutical compositions of metformin, which can be reconstituted in water prior to administration; process of manufacturing such compositions,, and their use in treating hyperglycemia and/or diabetes.

BACKGROUND OF THE INVENTION

Diabetes Mellitus is the most common of the serious metabolic diseases affecting humans. It has been estimated that there are over 200 million people that have diabetes in the world.

Metabolically, diabetes is characterized by an inappropriate elevation of blood glucose levels. In Type I Diabetes Mellitus, this is due to an absence of insulin in the individual. In Type II Diabetes Mellitus, although there is circulating insulin, its signal is not efficiently transduced via the insulin receptor, giving rise to insulin resistance, where the body responds less and less well to a given amount of insulin. Insulin is a peptide hormone which is produced by the Langerhorn islets in the pancreas. Insulin triggers increased glucose utilization, protein synthesis, and the formation and storage of neutral lipids. The present invention focuses on Type II Diabetes Mellitus, or non- insulin-dependent diabetes.

Diabetes Mellitus is also characterized by long term complications involving the eyes, nerves, kidneys and blood vessels. These diabetic complications include premature atherosclerosis, intercapillary glomerulosclerosis, retinopathy and neuropathy. The major cause of morbidity and mortality among diabetics is coronary heart disease.

The primary goal in the treatment of diabetes is to maintain blood glucose levels as close to normal as possible. For Type II diabetics, the first line of therapy for maintaining blood glucose level is modification of diet and lifestyle. The diabetic diet features restrictions on fat content and an increased intake of dietary fiber. Regular exercise is also emphasized to decrease weight and reduce the degree of insulin resistance. If diet and lifestyle modifications fail to control glucose levels, oral hypoglycemic therapy or insulin therapy is required to -control glucose levels and thus minimize complications related to the disease.

One of the compounds used to treat diabetes is metformin or its pharmaceutically acceptable salts. Metformin is a dimethyl biguanide having the formula:

The pharmaceutically acceptable salts of the formula:

in which A is the anion of the non-toxic salt are the preferred medicaments.

Metformin hydrochloride is a cohesive white powder which is highly soluble in water (>300 mg/ml at ambient temperature). The marketed metformin hydrochloride salt has a pronounced saline, bitter taste. Accordingly, it is usually marketed as a coated tablet wherein its coating is masked or is designed to mask any unpleasant taste.

Metformin, is currently marketed in U.S. as Glucophage^® tablets and extended release tablets (by Bristol-Myers Squibb Company) and in Europe in the form of Glucophage^® sachets containing powder for oral solution (by Merck).

U.S. Patent No. 3, 174,921 discloses various pharmaceutically acceptable salts of metformin, for example, phosphate, sulfate, hydrochloride, salicylate, maleate, benzoate, ethanedisulfonate, fumarate and glycolate.

U.S. Patent No. 6,031,004 discloses metformin salts of dibasic acids, such as fumarate and succinate, wherein the molar ratio of metformin:dibasic acid is 2: 1.

However, the most preferred metformin product is the hydrochloride salt.

U.S. Patent No. 6,890,957 discloses a liquid pharmaceutical composition for oral administration to a subject in need thereof which comprises a therapeutically effective amount of metformin or a pharmaceutically acceptable salt thereof in association with mineral acid. U.S. Patent No. 6,517,870 discloses oral formulations comprising a biguanide and an organic acid. The patent further discloses that oral formulation comprising a biguanide and an organic acid has less unpleasant tastes such as bitterness and saltiness.

International (PCT) publication No. WO2007/038979 discloses an effervescent metformin composition comprising pharmaceutically acceptable salt of metformin, an acid compound or an acid salt, an alkaline effervescent compound, compressible binders, and one or more other excipients.

U.S. Patent Publication No. 20090130215 Al discloses a stable granular preparation comprising biguanide compound, which does not solidify during storage. The formulations exemplified in the publication contain organic acid.

U.S. Patent No. 7,431,943 discloses a controlled release and taste masking composition containing one or more active principles inglobated in a three-component matrix structure, i.e. a structure formed by successive amphiphilic, lipophilic or inert matrices and finally inglobated or dispersed in hydrophilic matrices.

International (PCT) publication No. WO2004/082664 discloses a water-soluble tablet that includes a pharmaceutically acceptable salt of metformin which dissolves to form a clear solution. The publication exemplifies metformin tablets containing sodium citrate as the taste masking agent.

U.S. Patent No. 7,615,235 discloses a method of preparing a film-shaped or wafer shaped composition being not capable of disintegrating in an aqueous medium, comprising at least one matrix forming polymer comprising both at least one active substance having an unpleasant taste and at least one carbon dioxide substance which is not combined with an acid, wherein said unpleasant taste of said at least one active substance is reduced or suppressed.

The daily recommended starting dose of metformin is very high, 500 mg to 850 mg for children, adults and adolescents which is 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 as 3 divided doses. Thus, high bulk or large size dosage form may impair patient compliance specifically in case of children and elderly as small bulk dosage form and less administration frequency is usually recommended for them.

The non-compliance of the metformin dosage forms is further aggravated due to its unpleasant (bitter and salty) taste and high daily recommended dose, e.g. about 850 mg per dose in United States of America. Various attempts have been made in the prior art for masking bitterness of bitter drugs, for instance, for solid formulations, sugar coated tablets, film coated tablets, polymer coated tablets, capsules and the like are useful. Powders, fine granules and granules formulated by complexing bitter drug with resins, non-enteric coated formulation, spray-dried formulation with low melting point wax, formulation with lecithin and the like may also be used. For solutions, there are formulations with water- insoluble high molecular weight compound such as ethylcellulose and hydroxypropylmethylcellulose phthalate; formulations with acidic phospholipids or lyso-phospholipids; and formulations with a large amount of citric acid are also known.

Thus, the prior art references emphasize on using organic/mineral acids, or manufacturing the formulation by coating with polymers, formulating drug-polymer matrices, or complexing the drug with resins. However, these methods are not suitable at commercial level since the process requires continuous monitoring of processing parameters and inherently involves significant processing cost. The resulting formulations nevertheless, may not suitable enough for administration to special patient population (children and elderly).

Hence, there still exists a need to make palatable, easy to administer metformin formulations which are simple to manufacture and remain stable over the storage period.

SUMMARY OF THE INVENTION

In one general aspect there is provided a rapidly dispersible pharmaceutical composition comprising metformin or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of any organic/inorganic acid.

In another general aspect there is provided a rapidly dispersible tablet comprising metformin or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of any organic/inorganic acid.

Embodiments of the rapidly dispersible pharmaceutical composition may include one or more of the following features. For example, the pharmaceutical composition may include one or more pharmaceutically acceptable excipients selected from binders, fillers, lubricants, disintegrants, glidants, antioxidants, flavors, and the like. In another general aspect there is provided a rapidly dispersible pharmaceutical composition comprising metformin or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of any organic/inorganic acid and the composition dissolves or disperses in less than 1 minute, for example within 45 seconds in water at 37°C.

In another general aspect there is provided a rapidly dispersible pharmaceutical composition comprising metformin or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients; wherein the composition is free of any organic/inorganic acid and the amount of metformin or pharmaceutically acceptable salts thereof is at least 80% by total weight of the composition.

In another general aspect there is provided a stable rapidly dispersible pharmaceutical composition comprising metformin or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients; wherein the composition is free of any organic inorganic acid and the composition retains at least 80% of the potency of metformin or pharmaceutically acceptable salts thereof in the

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pharmaceutical composition after storage for three months at 40 C and 75% relative humidity.

In another general aspect there is provided a rapidly dispersible pharmaceutical composition comprising metformin or pharmaceutically acceptable salts thereof comprising one or more sweetener/s, one or more flavoring agent/s and optionally one or more pharmaceutically acceptable excipients; wherein the composition is free of any organic/inorganic acid.

In another general aspect there is provided a rapidly dispersible pharmaceutical composition comprising metformin or pharmaceutically acceptable salts thereof, about 2% to about 40% by weight of sweetener, and one or more pharmaceutically acceptable excipients; wherein the composition is free of any organic/inorganic acid.

In another general aspect there is provided a rapidly dispersible pharmaceutical composition comprising metformin or pharmaceutically acceptable salts thereof, one or more sweetener/s, one or more flavoring agent/s and optionally one or more pharmaceutically acceptable excipients; wherein the composition is free of any organic/inorganic acid and metformin or pharmaceutically acceptable salts thereof and the sweeteners are present in the composition in a ratio from about 1 :0.01 to about 1 :0.8 by weight. In another general aspect there is provided a rapidly dispersible pharmaceutical composition in the form of granules or powder or granules/powder filled in sachets comprising metformin or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients; wherein the composition is free of any organic/inorganic acid.

Embodiments of the rapidly dispersible pharmaceutical composition may include one or more of the following features. For example, the pharmaceutical composition may include one or more pharmaceutically acceptable excipients selected from binders, fillers, lubricants, disintegrants, glidants, antioxidants, flavors, and the like.

In another general aspect there is provided a process of preparing the rapidly dispersible pharmaceutical composition comprising metformin or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, the process comprising mixing metformin or pharmaceutically acceptable salts thereof with at least one sweetener and optionally one or more other pharmaceutically acceptable excipients.

In another general aspect there is provided a process for preparation of a stable rapidly dispersible pharmaceutical composition, which process comprises of-

(a) preparing a blend of metformin or pharmaceutically acceptable salts thereof, one or more sweetener/s, one or more flavoring agent/s, and optionally one or more pharmaceutically acceptable excipients;

(b) granulating the blend of step (a) using water to form granules; and

(c) formulating the granules prepared in step (b) into suitable dosage form,

wherein said composition is free of any organic/inorganic acid.

In another general aspect there is provided a method of treating hyperglycemia, the method comprising administering to a patient in need thereof a rapidly dispersible pharmaceutical composition comprising metformin or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of any organic/inorganic acid. The details of one or more embodiments of the invention are set forth in the description below. Other features, objects and advantages of the invention will be apparent from the description.

DETAILED DESCRD7TION OF THE INVENTION

The inventors of the present invention have surprisingly found that it is possible

^' to develop a palatable, easy to administer and taste masked formulation of metformin or its pharmaceutically acceptable salts without using any organic or mineral acid, and by using judicial combination of metformin and pharmaceutically acceptable excipients. Thus present inventors have simplified the formulation and process of making such formulation by avoiding unnecessary use of acids.

In particular, the present inventors have developed a pharmaceutical composition of metformin which can be reconstituted, dispersed or solubilized in water. The resulting composition is also palatable enough without employing any acid, particularly organic or inorganic acid.

Thus, the embodiments of the present invention relates to a rapidly dispersible pharmaceutical composition of metformin or pharmaceutically acceptable salts thereof with one or more pharmaceutically acceptable excipients; wherein the composition is free of any acid, preferably organic/inorganic acid.

The term "rapidly dispersible" as used herein means an uncoated composition that dissolves or disperses in water. The solution produced may be slightly opalescent due to added substances used in the manufacture of the composition.

In an embodiment, the rapidly dispersible pharmaceutical composition of the present invention dissolves or disperses in less than 1 minute in water at 37°C.

Suitable sweetener that can be used in the rapidly dispersible pharmaceutical composition of the present invention is such that it imparts a sweet taste but does not increase blood glucose level of the patient. Examples include sugar alcohol and non- nutritive sugars.

As used herein, the term sugar alcohol refers to reduced sugars. The preferred sugar alcohols are mono-saccharide alcohols and disaccharide alcohols. The monosaccharide alcohols have the formula HO-CH₂ (CHOH)_n -CH₂-OH, wherein n is 2-5. They also include tetritols, pentitols, hexitols and heptitols. Examples of sugar alcohols include erythritol, theritol, ribitol, arabinitol, xylitol, allitol, dulcitol, glucitol, sorbitol, mannitol, altritol, iditol, maltitol, lactitol, isomalt, hydrogenated starch hydrolysate and the like. The sugar alcohols, especially the monosaccharide alcohols, may be utilized as a racemic mixture or in the D or L form.

The non-nutritive sweeteners are sweet but are non-caloric. The non-nutritive sweetener used in the pharmaceutical composition may be selected from but not limited to aspartame, saccharin, saccharin sodium, stevioside, thaumatin, erythritol, sorbitol, xylitol, glycerin and mixtures thereof. Preferable sweetening agents are aspartame, saccharin, saccharin sodium and stevioside.

The amount of sweetener in the rapidly dispersible pharmaceutical composition ranges from about 2% to about 40% by weight, preferably less than about 15%, and more preferably less than 10% by weight of the composition.

The ratio (w/w) of the amount of metformin or pharmaceutically acceptable salt thereof to that of sweetener in the rapidly dispersible pharmaceutical composition ranges from about 1 :0.1 to about 1 :0.5, and more preferably from about 1 :0.01 to about 1 :0.08.

The rapidly dispersible pharmaceutical composition of metformin further may contain one or more antihyperglycemic agents. Antihyperglycemic agents (preferably oral), may be selected from, but not limited to, sulfonyl urea such as glyburide, glimepiride, glipizide, gluclazide, or chloropropamide or other known sulphonyl ureas; acarbose; miglitol; glucosidase inhibitor, such as acarbose; and thiazolidinediones such as troglitazone, pioglitazone, zorglitazone, englitazone, darglitazone and the like.

Pharmaceutical composition can be developed in the form of rapidly dispersible powder, granules, pellets, spherules, tablets, minitablets or those filled in sachets or capsules.

In a preferred embodiment, the rapidly dispersible pharmaceutical composition of the present invention is provided in the form of a sachet containing rapidly dispersible granules, and a water-soluble/dispersible tablet. The tablet can be dispersed or dissolved in water or any suitable edible solvent to prepare a solution or suspension of metformin which can be swallowed by patient.

It was found that the rapidly dispersible tablet comprising metformin or pharmaceutically acceptable salt, comprising disintegrating agents in both intragranular as well as extragranular portion, thereof and free of any acid, the resulting tablet may exhibit rapid disintegration and/or an acceptable dissolution pattern.

The rapidly dispersible pharmaceutical composition according to the present invention further may include pharmaceutically acceptable excipients comprising one or more fillers, binders, antioxidants, lubricants, disintegrants, glidants flavoring agents and the like.

Suitable fillers may include one or more of microcrystalline cellulose, starch, dibasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, dextrose, kaolin, magnesium carbonate, magnesium oxide; sugars such as lactose or sucrose; sugar alcohols such as mannitol, sorbitol, erythritol and the like.

Suitable disintegrants may include one or more of croscarmellose sodium, sodium starch glycolate, pregelatinized starch, sodium carboxymethyl cellulose, cross- linked polyvinylpyrrolidone and the like. The amount of disintegrant in the rapidly dispersible pharmaceutical composition may range from about 2% to about 30% by weight of the composition. In a preferred embodiment, the rapidly dispersible pharmaceutical composition comprises from about 0.5% to about 10% by weight of disintegrant in intra-granular portion and about 1% to about 25% by weight of disintegrant in extra-granular portion.

Suitable binders may include one or more of hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carbomers, dextrin, ethyl cellulose, methylcellulose, shellac, zein, gelatin, polymethacrylates, polyvinyl pyrrolidone, pregelatinized starch, sodium alginate, gums, synthetic resins and the like.

Suitable lubricants and/or glidants may include one or more of talc, metallic stearates such as magnesium stearate, calcium stearate, zinc stearate; colloidal silicon dioxide, finely divided silicon dioxide, stearic acid, hydrogenated vegetable oil, glyceryl palmitostearate, glyceryl monostearate, glyceryl behenate, polyethylene glycols, powdered cellulose, starch, sodium stearyl fumarate, sodium benzoate, mineral oil, magnesium trisilicate, kaolin; and the like. The amount of lubricant and/or glidant in the rapidly dispersible pharmaceutical composition ranges from about 0.5% to about 5% by weight of the composition.

Suitable antioxidant may include butylated hydroxanisole, sodium ascorbate, butylated hydroxytoluene, sodium metabisulfate, alpha tocopherol, malic acid, citric acid, ascorbic acid; and the like.

Suitable taste masking agents may include one or more of polymers. Most preferred polymers include one or more of cellulose acetate, polymethacrylates, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxylethyl cellulose; and the like. Suitable flavoring agents may include one or more of vanilla, strawberry, orange, mint, cherry, banana, mixed fruit; and the like.

In an embodiment, the rapidly dispersible pharmaceutical composition may contain organic/inorganic salts or minerals to aid in further improving the palatability of the composition. Suitable salts may include one or more of sodium chloride, potassium chloride, sodium carbonate, sodium bicarbonate, calcium chloride, magnesium chloride, taurine, zinc oxide, ferrous sulfate, copper sulfate, and the like. The preferable salt is sodium chloride.

The amount of metformin is a therapeutically effective amount and can be determined depending on the type and the degree of the disease, the age and the weight of the patient, and the like.

In an embodiment, the amount of metformin or pharmaceutically acceptable salt thereof present in the rapidly dispersible pharmaceutical composition of the present invention is at least 80% by total weight of the composition.

The process of preparing the rapidly dispersible pharmaceutical composition comprising preparing a powder blend or granules of metformin or pharmaceutically acceptable salts thereof, one or more sweetener/s and optionally with one or more pharmaceutically acceptable excipients.

The rapidly dispersible pharmaceutical composition can also be prepared by other granulation methods know to the skilled artisan, such as, for example, by extrusion granulation methods, extrusion-spheronization granulation methods, crushing granulation methods, dry granulation methods, fluidized bed granulation methods, tumbling granulation methods, high shear mixing granulation methods, wet compression methods, direct compression methods and the like.

In an embodiment, process of preparing the rapidly dispersible pharmaceutical composition of the present invention comprises the steps of-

(a) preparing a blend of metformin or pharmaceutically acceptable salts thereof, one or more sweetener/s, one or more flavoring agent/s and optionally one or more pharmaceutically acceptable excipients;

(b) granulating the blend of step (a) using water to form granules; and

(c) formulating the granules prepared in step (b) into suitable dosage form.

The resulting granules may then be optionally mixed with one or more pharmaceutically acceptable excipients, and filled in to capsules or sachets. The granules can also be optionally mixed with one or more pharmaceutically acceptable excipients, and compressed in to tablets, caplets, or mini-tablets. The term 'granule' as used herein also encompass the drug containing granule, pellet or core.

In a further embodiment, process of preparing a rapidly dispersible tablet comprises the steps of- (a) preparing a blend of metformin or pharmaceutically acceptable salts thereof, one or more sweetener/s, one or more disintegrating agent/s and optionally one or more pharmaceutically acceptable excipients;

(b) granulating the blend of step (a) using water to form granules;

(c) mixing the granules prepared in step (b) with one or more disintegrating agent/s, one or more flavoring agents, one or more lubricant/s and optionally one or more pharmaceutically acceptable excipients; and

(d) compressing the mixture prepared in step (c) into tablets.

The invention also provides a method of treating hyperglycemia, the method comprising administering to a patient in need thereof a rapidly dispersible pharmaceutical composition comprising metformin or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of any organic/inorganic acid.

The invention is further illustrated by the following examples which are provided to be exemplary of the invention and do not limit the scope of the invention. While the present invention has been described in terms of its specific embodiments, 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.

Example 1

Table 1

Procedure: Granules containing metformin hydrochloride and aspartame are prepared using water. The granules are then mixed with orange flavour and filled into sachets. Example 2

Table 2

Procedure: Dry mix containing metformin hydrochloride, crospovidone (in part quantity) and aspartame was granulated using water. The granules are then mixed with crospovidone (remaining quantity), mint flavour, lubricated with sodium stearyl fumarate and compressed to form tablets.

Example 3: Stability study on composition of the invention

Table 3

BQL - Below quantification limit

ND - Not detected

RRT - Relative retention time

The results of stability study indicates that the composition of the invention remains stable and retains at least 80% of the potency of metformin or pharmaceutically acceptable salts thereof in the pharmaceutical composition after

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storage for three months at 40 C and 75% relative humidity. While the invention has been described in terms of its specific embodiments, 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.

Claims

We claim:

1. A rapidly dispersible pharmaceutical composition comprising metformin or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of any organic/inorganic acid.

2. The rapidly dispersible pharmaceutical composition as claimed in claim 1 further comprising one or more sweeteners.

3. The rapidly dispersible pharmaceutical composition as claimed in claim 2, wherein the sweeteners comprises one or more of aspartame, saccharin, saccharin sodium, stevioside, thaumatin, erythritol, sorbitol, xylitol, glycerin and sugar alcohols.

4. The rapidly dispersible pharmaceutical composition as claimed in claim 2, wherein the sweeteners comprises from about 2% to about 40% by weight of the composition.

5. The rapidly dispersible pharmaceutical composition as claimed in claim 2, wherein the metformin or pharmaceutically acceptable salts thereof and the sweeteners are present in the composition in a ratio from about 1 :0.01 to about 1 :0.8 by weight.

6. The rapidly dispersible pharmaceutical composition as claimed in claim 1 , wherein the composition is in the form of powder, granules, pellets, tablets, caplets, mini- tablets, and sachets.

7. The rapidly dispersible pharmaceutical composition as claimed in claim 1 , wherein the metformin or pharmaceutically acceptable salts thereof is present in at least 80% by total weight of the composition.

8. The rapidly dispersible pharmaceutical composition as claimed in claim 1 , wherein the composition dissolves or disperses in less than 1 minute in water at 37°C.

9. The rapidly dispersible pharmaceutical composition as claimed in claim 1 , wherein the composition retains at least 80% of the potency of metformin or pharmaceutically acceptable salts thereof in the pharmaceutical composition after storage for three o

months at 40 C and 75% relative humidity.

10. A process for preparing a rapidly dispersible pharmaceutical composition as claimed in claim 1, the process comprising mixing metformin or pharmaceutically acceptable salts thereof with at least one sweetener and optionally one or more other pharmaceutically acceptable excipients.

1 1. A process for the preparation of a stable rapidly dispersible pharmaceutical composition of metformin or pharmaceutically acceptable salts thereof, the process comprising:

(b) granulating the blend of step (a) using water to form granules; and

(c) formulating the granules prepared in step (b) into a suitable dosage form, wherein the composition is free of any organic/inorganic acid.

12. A sachet comprising rapidly dispersible granules comprising at least 80% by weight of metformin or pharmaceutically acceptable salts thereof, and about 2% to about 40% by weight of one or more sweeteners, wherein the sachet is free of any organic/inorganic acid.

13. The sachet as claimed in claim 12, wherein the metformin or pharmaceutically acceptable salts thereof comprises about 82.3% by weight of the granules.

14. The sachet as claimed in claim 12, wherein the sweetener comprises about 16.46% by weight of the granules.

15. A rapidly dispersible tablet comprising:

(a) at least 80% by weight of metformin or pharmaceutically acceptable salts thereof;

(b) about 1% to about 20% by weight of one or more sweeteners;

(c) about 2% to about 30% by weight of one or more disintegrants; and (d) about 0.5% to about 5% by weight of one or more lubricants;

wherein the composition is free of any organic/inorganic acid.

16. The rapidly dispersible tablet as claimed in claim 15, wherein the metformin or pharmaceutically acceptable salts thereof comprises about 83.33% by weight of the tablet.

17. The rapidly dispersible tablet as claimed in claim 15, wherein the sweetener comprises about 5.58% by weight of the tablet.

18. The rapidly dispersible tablet as claimed in claim 15, wherein the disintegrant comprises about 6.33% by weight of the tablet.

19. A method of treating hyperglycemia, the method comprising administering to a patient in need thereof a rapidly dispersible pharmaceutical composition comprising metformin or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of any organic/inorganic acid.