WO2016001843A1

WO2016001843A1 - Extended-release gastroretentive tablets of voglibose

Info

Publication number: WO2016001843A1
Application number: PCT/IB2015/054916
Authority: WO
Inventors: Ravish Sharma; Anuj Kumar Fanda; Kumaravel Vivek; Romi Barat Singh
Original assignee: Sun Pharmaceutical Industries Limited
Priority date: 2014-06-30
Filing date: 2015-06-30
Publication date: 2016-01-07

Abstract

The present invention relates to extended-release gastroretentive tablets of voglibose and processes for their preparation.

Description

EXTENDED-RELEASE GASTRORETENTIVE TABLETS OF VOGLIBOSE

Field of the Invention

Background of the Invention

EP Patent No. 1 561 458 discloses an orally rapidly disintegrable solid preparation comprising voglibose, a sugar or sugar alcohol, and a low-substituted hydroxypropyl cellulose having 5% by weight or more to less than 7% by weight of hydroxypropoxyl group.

PCT Publication No. WO 2013/115742 discloses a composition comprising voglibose, characterized in that said formulation comprises talc, magnesium stearate, polyethylene glycol, silicon dioxide, sodium benzoate, potassium benzoate, stearic acid, sodium stearyl fumarate and/or a combination thereof as lubricant.

PCT Publication No. WO 2013/115741 discloses a composition comprising voglibose, acarbose, or miglitol characterized in that the ratio of bulk density to compressed density of the composition is minimum 0.75, and particle size distribution value of voglibose, acarbose, or miglitol is in the range of 10 to 600 μιη.

Due to the digestion of carbohydrates occurring mostly in the upper jejunum, a post-prandial rise in blood glucose is generally seen within one hour after the start of a meal. Therefore, there is a need to administer voglibose prior to a mealtime to achieve the maximal effect. Voglibose is commercially available as immediate release tablets with a dosage administration of thrice daily just before the start of every meal. Further, the half- life of voglibose is short, thereby necessitating frequent administration, leading to a high level of patient non-compliance.

In view of this, extended-release tablets of voglibose remain highly desirable over immediate-release tablets. Further, prolongation of gastric residence time can be used as one of the ways to design extended-release tablets of voglibose. This helps reduce the inter-subject variability leading to a more predictable bioavailability. It further reduces the number of doses required, leading to enhanced patient compliance.

EP Patent No. 1 022 028 discloses a prolonged gastrointestinal residence type preparation of -glucosidase inhibitor, such as voglibose, as a gastrointestinal mucosa- adherent preparation, an intragastric floating preparation, or an intragastric residence preparation utilizing a shape-memory type polymer. The sustained-release oral preparation comprises a matrix of polyglycerol fatty acid ester and/or a lipid.

There still exists a need in the art for robust, easy to manufacture, and industrially reproducible extended-release gastroretentive tablets of voglibose. Also, there remains a need in the art for once daily extended-release gastroretentive tablets of voglibose.

The present invention provides extended-release gastroretentive tablets of voglibose, wherein voglibose is released over a prolonged period of time for enhanced therapeutic efficacy. Further, the tablets of the present invention have a once daily dosage regimen, resulting in improved patient compliance.

Summary of the Invention

The compositions of the present invention are a significant advance over conventional immediate-release tablets of voglibose as these compositions provide improved patient compliance to the dosage regimen with optimum clinical benefits.

Detailed Description of the Invention

A first aspect of the present invention provides an extended-release gastroretentive tablet of voglibose for once-a-day therapy comprising voglibose and one or more release- controlling polymers.

According to one embodiment of the above aspect, the extended-release gastroretentive tablet of voglibose further comprises one or more water-swellable polymers.

According to another embodiment of the above aspect, the extended-release gastroretentive tablet of voglibose includes an immediate-release layer of the voglibose.

A second aspect of the present invention provides a process for the preparation of an extended-release gastroretentive tablet of voglibose, wherein the process comprises:

(i) blending or granulating voglibose with one or more release-controlling polymers, one or more water-swellable polymers, and one or more pharmaceutically acceptable excipients; (ii) compressing the blend or granules of step (i) to form a tablet core; and

(iii) optionally applying a coating composition comprising voglibose, one or more film-forming polymers, and one or more pharmaceutically acceptable coating additives over the tablet core of step (ii).

A third aspect of the present invention provides a process for the preparation of an extended-release gastroretentive tablet of voglibose, wherein the process comprises:

(i) blending or granulating voglibose with one or more water-swellable

polymers and one or more pharmaceutically acceptable excipients;

(ii) compressing the blend or granules of step (i) to form a tablet core;

(iii) dissolving or dispersing one or more release-controlling polymers and one or more pharmaceutically acceptable coating additives in a suitable solvent;

(iv) applying the coating composition of step (iii) over the tablet core of step (ii); and

(v) optionally applying a coating composition comprising voglibose, one or more film-forming polymers, and one or more pharmaceutically acceptable coating additives over the coated tablet core of step (iv).

A fourth aspect of the present invention provides a process for the preparation of an extended-release gastroretentive tablet of voglibose, wherein the process comprises:

(i) blending or granulating one or more water-swellable polymers with one or more pharmaceutically acceptable excipients;

(ii) compressing the blend or granules of step (i) to form a tablet core;

(iii) dissolving or dispersing voglibose, one or more film-forming polymers, and one or more pharmaceutically acceptable coating additives in a suitable solvent;

(iv) applying the coating composition of step (iii) over the tablet core of step (ii);

(v) dissolving or dispersing one or more release-controlling polymers and one or more pharmaceutically acceptable coating additives in a suitable solvent;

(vi) applying the coating composition of step (v) over the coated tablet core of step (iv); and

(vii) optionally applying a coating composition comprising voglibose, one or more film-forming polymers, and one or more pharmaceutically acceptable coating additives over the coated tablet core of step (vi). A fifth aspect of the present invention provides a process for the preparation of an extended-release gastroretentive tablet of voglibose, wherein the process comprises:

(ii) blending or granulating voglibose with one or more pharmaceutically

acceptable excipients;

(iii) compressing the blend or granules of step (i) and the blend or granules of step (ii) to form a bi-layered tablet core;

(iv) dissolving or dispersing one or more release-controlling polymers and one or more pharmaceutically acceptable coating additives in a suitable solvent;

(v) applying the coating composition of step (iv) over the bi-layered tablet core of step (iii); and

(vi) optionally applying a coating composition comprising voglibose, one or more film-forming polymers, and one or more pharmaceutically acceptable coating additives over the coated bi-layered tablet core of step (v).

A sixth aspect of the present invention provides a method of treating diabetes by administering once-a-day extended-release gastroretentive tablet of voglibose comprising voglibose and one or more release-controlling polymers.

According to another embodiment of the above aspect, the extended-release gastroretentive tablet of voglibose includes an immediate -release layer of the voglibose.

The term "voglibose," as used herein, refers to (\S,2S,3R,4S,5S)-5-(\,3- dihydroxypropan-2-ylamino)- 1 -(hydroxymethyl)cyclohexane- 1 ,2,3 ,4-tetraol . It further includes salts, polymorphs, hydrates, solvates, prodrugs, chelates, and complexes thereof.

The term "gastroretentive," as used herein, means that upon oral administration at least a portion of the tablet remains in the stomach for a period that is longer than the normal emptying time from the stomach, i.e., longer than about 2 hours, particularly longer than about 3 hours, and more particularly longer than about 4, 6, 8, or 10 hours. The term "extended-release," as used herein, refers to voglibose release over a prolonged period of time, e.g., more than about 4, 6, 8, 16, or 24 hours following ingestion.

The term "immediate-release," as used herein, refers to voglibose release over a short period of time, e.g., within about 1 hour, preferably within about 30 minutes following ingestion.

The term "about," as used herein, refers to any value which lies within the range defined by a variation of up to ±10% of the value.

The tablet core of the present invention may be a single layer or a multi-layered tablet core. In the multi -layered tablet core, the layers can be compressed in any order.

The extended-release gastroretentive tablets of the present invention may comprise an outer immediate-release layer of voglibose. This outer layer provides the initial burst release of voglibose, and after a predetermined time interval another release of voglibose occurs resulting in a pulsatile delivery. The time interval between the two releases can be controlled by the amount of release-controlling polymer in the extended-release layer and the thickness of the extended-release layer.

The extended-release tablets of the present invention utilize a gastroretentive floating system which remains buoyant in the stomach and releases voglibose over a prolonged period of time. The gastroretentive floating systems of the present invention have a floatation time up to 24 hours.

The term "water-swellable polymer," as used herein, refers to a polymer which expands upon contact with water. Suitable examples of water-swellable polymers are selected from the group comprising carboxyvinyl polymers (such as those available under the trade name Carbopol^®); cellulose derivatives e.g., hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, methyl cellulose, sodium carboxymethyl cellulose, hydroxyethylmethyl cellulose, and microcrystalline cellulose; polyethylene derivatives e.g., polyethylene glycol and polyethylene oxide; gums e.g., guar gum, locust bean gum, tragacanth, carrageenan, alginic acid, gum acacia, gum arabic, gellan gum, and xanthan gum; proteins e.g., gelatin, casein, and zein; saccharides e.g., dextrin, dextran, polygalacturonic acid, xylan, arabinoxylan, arabinogalactan, pectin or its derivatives, and starch or its derivatives; polyvinyl derivatives e.g., polyvinyl alcohol, polyvinyl pyrrolidone and polyvinyl acetal diethylaminoacetate; polymethacrylate copolymer and acrylic/methacrylic acid copolymers; chitosan; cross-linked polyvinylpyrrolidone (such as those available under the trade name Polyyplasdone^®); and combinations thereof.

The term "release-controlling polymer," as used herein, refers to a polymer that helps to control the release of voglibose. Suitable examples of release-controlling polymers are selected from the group comprising cellulose derivatives e.g., ethylcellulose, hydroxypropylmethyl cellulose (such as Methocel^® K100), cellulose acetate, cellulose acetate phthalate, cellulose acetate mellitate, cellulose acetate succinate,

hydroxypropylmethyl cellulose phthalate, hydroxypropylmethyl cellulose acetate succinate, and carboxymethyl cellulose ether; polyvinyl acetate phthalate; polyester of styrene and maleic acid copolymer; polyester of vinylether and maleic acid copolymer; vinylacetate and crotonic acid copolymer; copolymers of methacrylic acid and ethylacrylate; copolymers of methacrylic acid and methacrylate (e.g., Eudragit^® L 100, Eudragit^® L 100-55, Eudragit^® L 30 D-55, and Eudragit^® S 100); copolymers of methacrylate/trimethyl ammonioethylmethacrylate (e.g., Eudragit^® RL PO, Eudragit^® RL 100, Eudragit^® RL 30 D, Eudragit^® RS PO, Eudragit^® RS 100, and Eudragit^® RS 30 D); neutral polymer of methacrylate (e.g., Eudragit^®NE 30 D, and Eudragit^®NE 40 D);

carboxy vinyl polymers (such as those available under the trade name Carbopol^®);

polyethylene derivatives e.g., polyethylene oxide; gums e.g., guar gum, locust bean gum, tragacanth, carrageenan, alginic acid, gum acacia, gum arabic, gellan gum, and xanthan gum; waxes, e.g., Compritol^®, Lubritab^®, and Gelucires^®; lipids; fatty acids or their salts/derivatives; a mixture of polyvinyl acetate and polyvinyl pyrrolidone, e.g., Kollidon^® SR; and combinations thereof. The percentage of extended-release polymer in the extended-release layer and thickness of the extended-release layer is critical for controlling the release of voglibose. The amount of the extended-release polymer used in the present invention may vary from about 40% to about 90% w/w based on the total weight of the extended release layer.

The term "pharmaceutically acceptable excipients," as used herein, refers to excipients that are routinely used in pharmaceutical compositions. Suitable examples of pharmaceutically acceptable excipients are selected from the group consisting of binders, diluents, disintegrating agents, lubricants, glidants, osmotic agents, effervescent agents, and combinations thereof. Suitable binders are selected from the group comprising celluloses e.g., methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, ethyl cellulose, and sodium carboxy methyl cellulose; polymethacrylates;

carboxyvinyl polymers; gums e.g., acacia, alginic acid, sodium alginate, tragacanth, and guar gum; sugars e.g., lactose, liquid glucose, sucrose, and dextrin; polydextroses; starch or its derivatives; kaolin; povidone; copovidone; polyethylene oxide; polyvinyl pyrrolidone; polyvinyl alcohol; poly-N-vinyl amide; polyethylene glycol; gelatin;

polypropylene glycol; glyceryl behenate; oils e.g., hydrogenated vegetable oil, castor oil, and sunflower oil; zein; paraffin; higher aliphatic alcohols; higher aliphatic acids; fatty acid esters; fatty acid glycerides; agar; chitosan; maltodextrin; magnesium aluminum silicate; inulin; waxes; and mixtures thereof.

Suitable diluents are selected from the group comprising microcrystalline cellulose, silicified microcrystalline methyl cellulose, ethyl cellulose, lactose, dibasic or tribasic calcium phosphate, cellulose acetate, confectioner's sugar, compressible sugar, sugar spheres, dextrates, dextrin, dextrose, fructose, maltose, sodium chloride, lactitol, maltitol, xylitol, erythritol, isomalt, sorbitol, maltodextrin, mannitol, sucrose, fructose, glyceryl palmitostearate, semithicone, magnesium aluminum silicate, starch,

pregelatinized starch, sulfobutylether ?-cyclodextrin, polymethacrylates, talc, trehalose, ammonium alginate, calcium carbonate, calcium silicate, calcium carbonate, magnesium carbonate, magnesium oxide, calcium sulphate, and mixtures thereof.

Suitable disintegrating agents are selected from the group comprising cellulose or its derivatives e.g., low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, carboxymethyl calcium cellulose, and microcrystalline cellulose; starches e.g., starch, pregelatinized starch, hydroxypropyl starch, sodium carboxymethyl starch, and sodium starch glycolate; ion-exchange resins e.g., polacrillin potassium; gums e.g., guar gum, sodium alginate, calcium alginate, and alginic acid; clays e.g., bentonite and veegum; povidone; cross-linked polyvinyl pyrrolidone; formalin-casein; chitosan; magnesium aluminum silicate; colloidal silicon dioxide; and mixtures thereof.

Suitable lubricants are selected from the group comprising magnesium stearate, aluminum stearate, calcium stearate, zinc stearate, sodium stearyl fumarate, talc, colloidal silica, polyethylene glycol, polyvinyl alcohol, glyceryl behenate, glyceryl monostearate, glyceryl palmitostearate, potassium benzoate, sodium benzoate, mineral oil, palmitic acid, myristic acid, stearic acid, hydrogenated vegetable oil, hydrogenated soybean oil, stearyl alcohol, leucine, sodium lauryl sulfate, ethylene oxide polymers, poloxamer,

octyldodecanol, and mixtures thereof.

Suitable glidants are selected from the group comprising powdered cellulose, starch, talc, tribasic calcium phosphate, calcium silicate, magnesium silicate, magnesium trisilicate, colloidal silicon dioxide, silicon hydrogels, and mixtures thereof.

Suitable osmotic agents are selected from the group comprising water soluble salts of inorganic acids e.g., magnesium chloride, magnesium sulfate, lithium chloride, sodium chloride, potassium chloride, lithium hydrogen phosphate, sodium hydrogen phosphate, potassium hydrogen phosphate, lithium dihydrogen phosphate, sodium dihydrogen phosphate, and potassium dihydrogen phosphate; water soluble salts of organic acids e.g., sodium acetate, potassium acetate, magnesium succinate, sodium benzoate, sodium citrate, and sodium ascorbate; non-ionic organic compounds with high water solubility e.g., carbohydrates such as mannitol, sorbitol, arabinose, ribose, xylose, glucose, fructose, mannose, galactose, sucrose, maltose, lactose, and raffinose; water-soluble amino acids e.g., glycine, leucine, alanine, or methionine; urea and its derivatives; and mixtures thereof.

Effervescent agents comprise an acid source and a base source. A suitable acid source is selected from the group comprising citric acid, fumaric acid, tartaric acid, ascorbic acid, malic acid, acetylsalicylic acid, sodium dihydrogen citrate, disodium hydrogen citrate, nicotinic acid, adipic acid, or mixtures thereof. A suitable base source is selected from the group comprising sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, amino acid-alkali metal carbonate derivatives, and mixtures thereof.

The tablet core of the present invention can be prepared by any method known in the art such as by direct compression, dry granulation, wet granulation, or melt granulation.

The immediate -release layer of the present invention comprises voglibose, one or more film-forming polymers, and one or more coating additives.

Pharmaceutically acceptable coating additives may be selected from the group consisting of binders, diluents, plasticizers, opacifiers, coloring agents, lubricants, and pore -formers. Suitable film-forming polymers are selected from the group comprising cellulose or its derivatives e.g., hydroxypropylmethyl cellulose, hydroxypropyl cellulose, ethyl cellulose, methyl cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, cellulose acetate, hydroxypropylmethyl cellulose phthalate, cellulose acetate phthalate, and cellulose acetate trimellitate; waxes e.g., polyethylene glycol; methacrylic acid polymers e.g., Eudragit^®; and polyvinyl pyrrolidone.

Alternatively, commercially available coating compositions comprising film-forming polymers marketed under various trade names, such as Opadry^® may also be used.

Suitable plasticizers are selected from the group comprising triethyl citrate, dibutyl sebacate, acetylated triacetin, tributyl citrate, glycerol tributyrate, acetyl tributyl citrate, diacetylated monoglyceride, rapeseed oil, olive oil, sesame oil, glycerin, sorbitol, diethyl oxalate, diethyl phthalate, diethyl malate, diethyl fumarate, dibutyl succinate, diethyl malonate, dioctyl phthalate, and combinations thereof.

Suitable opacifiers are selected from the group comprising titanium dioxide, manganese dioxide, iron oxide, silicon dioxide, and combinations thereof.

Suitable pore-formers are selected from the group comprising polyethylene glycols e.g., polyethylene glycol 6000 and polyethylene glycol 400; celluloses e.g.,

hydroxypropylmethyl cellulose, hydroxypropyl cellulose, and methyl cellulose;

polysaccharides e.g., alginates, xanthan gum, chitosan, carrageenan, and dextran;

polyalkylene oxides e.g., polyethylene oxide; vinyl acetate copolymers; methacrylic acid copolymers; maleic anhydride/methyl vinyl ether copolymers; carboxyvinyl polymers; and combinations thereof.

The present invention also encompasses a seal -coating layer present in between the core and extended-release layer and/or between the extended-release layer and immediate- release layer. The seal-coating layer may also be present as the outermost layer.

The seal-coating layer may comprise one or more film-forming polymers, and one or more coating additives.

Layering may be performed by applying the coating composition as a solution or suspension using any conventional coating technique known in the art, such as spray coating in a coating pan or fluidized bed processor, or dip coating.

Solvents used for wet granulation and for preparing the coating solution or dispersion are selected from the group comprising methylene chloride, isopropyl alcohol, acetone, methanol, ethanol, purified water, ethyl acetate, acetic acid, glycols,

dichloromethane, dimethylformamide, dimethyl sulfoxide, chloroform, toluene, ethoxyethyl acetate, ethylene glycol monoacetate, ethyl lactate, monoethyl acetate, methyl ethyl ketone, or mixtures thereof.

The extended-release gastroretentive tablet of the present invention may further include one or more anti -diabetic drugs such as acarbose, miglitol, metformin, repaglinide, nateglinide, glibenclamide, glimepride, glipizide, gliclazide, chloropropamide, tolbutamide, phenformin, aloglitin, sitagliptin, linagliptin, saxagliptin, rosiglitazone, pioglitazone, troglitazone, faraglitazar, englitazone, darglitazone, isaglitazone, zorglitazone, liraglutide, muraglitazar, peliglitazar, tesaglitazar, canagliflozin, dapagliflozin, remogliflozin, sergliflozin, or any other known anti-diabetic drug.

The following examples represent various embodiments according to the present invention. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention, as many variations thereof are possible without departing from the spirit and scope of the invention.

EXAMPLES

Example 1

Ingredients Quantity (mg)

Tablet Core

Voglibose 2.88

Microcrystalline cellulose 457.12

Crospovidone 80.00

Carboxyvinyl polymer 48.00

Hydroxypropylmethyl cellulose 160.00

Polyvinylpyrrolidone 40.00

Colloidal silica 4.00

Magnesium stearate 8.00

Purified water q.s.

Extended-Release Layer

Ethyl cellulose 24.00

Hydroxypropylmethyl cellulose 16.00

Purified water q.s.

Isopropyl alcohol q.s.

Immediate-Release Layer

Voglibose 0.20

Hydroxypropylmethyl cellulose 39.80

Purified water q.s.

Isopropyl alcohol q.s.

Total Weight of Tablet 880.00 Procedure:

Tablet core

1. Voglibose and polyvinylpyrrolidone were dissolved in purified water to form a solution.

2. Microcrystalline cellulose and hydroxypropylmethyl cellulose were granulated with the solution of step 1.

3. The granules of step 2 were blended with a mixture of crospovidone, carboxyvinyl polymer, and colloidal silica.

4. The blend of step 3 was lubricated with magnesium stearate.

5. The lubricated blend of step 4 was compressed into a tablet core.

Extended-release layer

6. Ethyl cellulose and hydroxypropylmethyl cellulose were dispersed into a solution of purified water and isopropyl alcohol.

7. The tablet core of step 5 was coated with the dispersion of step 6 to form an

extended-release coated tablet core.

Immediate-release layer

8. Voglibose and hydroxypropylmethyl cellulose were dispersed into a solution of purified water and isopropyl alcohol.

9. The coated tablet core of step 7 was coated with the dispersion of step 8.

Example 2

Procedure:

Tablet core

1. Microcrystalline cellulose, crospovidone, carboxyvinyl polymer,

hydroxypropylmethyl cellulose, polyvinylpyrrolidone, and colloidal silica were sifted together and mixed.

2. The mixture of step 1 was blended with magnesium stearate.

3. The blend of step 2 was compressed into a tablet core.

Voglibose layer

4. Voglibose and hydroxypropymethyl cellulose were dispersed into a solution of purified water and isopropyl alcohol.

5. The tablet core of step 3 was coated with the dispersion of step 4. Extended-release layer

6. Polyethylene glycol 6000 and polyethylene glycol 400 were dissolved in purified water to form a solution.

7. The solution of step 6 was mixed with acetone.

8. Cellulose acetate and triacetin were dispersed into the solution of step 7.

9. The coated tablet core of step 5 was coated with the dispersion of step 8.

Immediate-release layer

10. Voglibose and hydroxypropylmethyl cellulose were dispersed into a solution of purified water and isopropyl alcohol.

11. The coated tablet core of step 9 was coated with the dispersion of step 10.

Example 3

Procedure:

Tablet core - First layer

1. Microcrystalline cellulose, carboxyvinyl polymer, hydroxypropymethyl cellulose, polyvinylpyrrolidone, crospovidone, and colloidal silica were sifted together and mixed.

2. The mixture of step 1 was blended with magnesium stearate.

Tablet core - Second layer

3. Voglibose and polyvinylpyrrolidone were dissolved in purified water.

4. Microcrystalline cellulose and hydroxypropymethyl cellulose were granulated with solution of step 3.

5. The granules of step 4 were blended with colloidal silica and magnesium stearate.

6. The blends of step 2 and step 5 were compressed into a bi-layered tablet core.

Extended-release layer

7. Ethyl cellulose and hydroxypropylmethyl cellulose were dispersed into a solution of purified water and isopropyl alcohol.

8. The bi-layered tablet core of step 6 was coated with the dispersion of step 7.

Immediate-release layer

9. Voglibose and hydroxypropylmethyl cellulose were dispersed into a solution of purified water and isopropyl alcohol.

10. The coated bi-layered tablet core of step 8 was coated with the dispersion of step 9.

Examples 4-5

Procedure:

1. Voglibose was mixed with colloidal silicon dioxide and a portion of lactose. 2. Hydroxypropylmethyl cellulose, carboxyvinyl polymer, remaining portion of lactose, crosslinked polyvinylpyrolidone, and magnesium stearate were mixed together.

3. The mix of step 1 was blended with the mix of step 2.

4. The blend of step 3 was compressed into a tablet.

Examples 6-7

Procedure:

1. Voglibose was mixed with colloidal silicon dioxide and a portion of

microcrystalline cellulose.

2. Hydroxypropylmethyl cellulose, carboxyvinyl polymer, remaining portion of microcrystalline cellulose, crosslinked polyvinylpyrolidone, and magnesium stearate were mixed together.

3. The mix of step 1 was blended with the mix of step 2.

4. The blend of step 3 was compressed into a tablet.

In-Vitro Release Studies

The in-vitro dissolution of the extended release tablets of voglibose prepared as per Examples 6-7 were determined using a USP type II apparatus at 50 rpm, in 900 mL of 0. IN HCl using 10 mesh sinkers at 37°C. The results of the release studies are represented in Table 1. Table 1: Percentage (%) of the In-Vitro Voglibose Release in USP Type II Apparatus (Media: 0.1N HCl. 900 mL. and 50 rpm)

Claims

We claim:

1. An extended-release gastroretentive tablet of voglibose for once-a-day therapy comprising voglibose and one or more release -controlling polymers.

2. The extended-release gastroretentive tablet of claim 1, wherein the release- controlling polymer is selected from the group comprising cellulose derivatives, polyvinylacetate phthalate, polyester of styrene and maleic acid copolymer, polyester of vinylether and maleic acid copolymer, vinylacetate and crotonic acid copolymer, copolymers of methacrylic acid and ethylacrylate, copolymer of methacrylic acid and methacrylate, copolymer of methacrylate/trimethyl ammonioethylmethacrylate, neutral polymer of methacrylate, carboxyvinyl polymers; polyethylene derivatives, gums, waxes, lipids, fatty acids or their salts/derivatives, a mixture of polyvinyl acetate and polyvinyl pyrrolidone, and combinations thereof.

3. The extended-release gastroretentive tablet of claim 1, wherein the tablet comprises one or more water-swe liable polymers.

4. The extended-release gastroretentive tablet of claim 3, wherein the water-swellable polymer is selected from the group comprising carboxyvinyl polymers; cellulose derivatives; polyethylene derivatives; gums; proteins; saccharides; polyvinyl derivatives; polymethacrylate copolymer; acrylic/methacrylic acid copolymer; chitosan; cross-linked polyvinylpyrrolidone, and combinations thereof.

5. The extended-release gastroretentive tablet of the preceding claims, wherein the tablet further comprises pharmaceutically acceptable excipients selected from the group consisting of binders, diluents, disintegrating agents, lubricants, glidants, osmotic agents, effervescent agents, and combinations thereof.

6. A process for the preparation of an extended-release gastroretentive tablet of voglibose, wherein the process comprises:

(i) blending or granulating voglibose with one or more water-swellable

polymers, one or more release -controlling polymers; and one or more pharmaceutically acceptable excipients;

(ii) compressing the blend or granules of step (i) to form a tablet core; and (iii) optionally applying a coating composition comprising voglibose, one or more film-forming polymers, and one or more pharmaceutically acceptable coating additives over the tablet core of step (ii).

7. A process for the preparation of an extended-release gastroretentive tablet of voglibose, wherein the process comprises:

(i) blending or granulating voglibose with one or more water-swellable

polymers and one or more pharmaceutically acceptable excipients; (i) compressing the blend or granules of step (i) to form a tablet core;

(ii) dissolving or dispersing one or more release-controlling polymers and one or more pharmaceutically acceptable coating additives in a suitable solvent; (iii) applying the coating composition of step (iii) over the tablet core of step (ii); and

(iv) optionally applying a coating composition comprising voglibose, one or more film-forming polymers, and one or more pharmaceutically acceptable coating additives over the coated tablet core of step (iv).

8. A process for the preparation of an extended-release gastroretentive tablet of voglibose, wherein the process comprises:

(ii) compressing the blend or granules of step (i) to form a tablet core;

(iii) dissolving or dispersing voglibose with one or more film-forming polymers in a suitable solvent;

(iv) applying the coating composition of step (iii) over the tablet core of step (ii); (v) dissolving or dispersing one or more release-controlling polymers and one or more pharmaceutically acceptable coating additives in a suitable solvent; (vi) applying the coating composition of step (v) over the coated tablet core of step (iv); and

(vii) optionally applying a coating composition comprising voglibose, one or more film-forming polymers, and one or more pharmaceutically acceptable coating additives over the coated tablet core of step (vi).

9. A process for the preparation of an extended-release gastroretentive tablet of voglibose, wherein the process comprises:

(ii) blending or granulating voglibose with one or more pharmaceutically

acceptable excipients; (iii) compressing the blend or granules of step (i) and the blend or granules of step (ii) to form a bi-layered tablet core;

(iv) dissolving or dispersing one or more release-controlling polymers and one or more pharmaceutically acceptable coating additives in a suitable solvent; (v) applying the coating composition of step (iv) over the bi-layered tablet core of step (iii); and

10. A method of treating diabetes by administering the once-a-day extended-release gastroretentive tablet of voglibose of claim 1.

11. An extended-release gastroretentive tablet of voglibose for once-a-day therapy comprising voglibose and one or more release -controlling polymers which releases 10- 25% of voglibose within 30 min, 30-50% of voglibose within 2 hours, and 80-100% within 12 hours.