FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
THE PROVISIONAL SPECIFICATION
(See section 10)
i. Solid oral dosage form having Antidiabetic drug combination.
2. CADILA PHARMACEUTICALS LTD., "CADILA CORPORATE CAMPUS", SARKHEJ-DHOLKA ROAD, BHAT, AHMEDABAD, 382210, GUJARAT, INDIA, AN INDIAN COMPANY.
3. THE FOLLOWING SPECIFICATION DESCRIBES AND ASCERTAINS THE NATURE OF THIS INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED.

Title : Solid oral dosage form having Antidiabetic drug combination
Field of invention: -
The present invention relates to solid oral dosage form (tablets) for the treatment of non-insulin dependant diabetes (Diabetes II) using a combination of antidiabetic drugs (hypoglycemic)

Background of the invention: -
Monotherapy with an oral antidiabetic is an effective way of treatment continuing for many years. However the efficacy is reported to decrease with time. Since sulphonylureas and biguanides have complementary mode of action, combined therapy is now an established form of the treatment for Diabetes II.
Tables having combination of antidiabetic drug eg. Metformin and glibenclamide have advantage of patient compliance.
Patents W097/17975 and AU199954179 B2 disclosed this combination for treatment of Diabetes II with optimum therapeutic ratio of both drugs. Patent AUl99954179 B2 disclosed tablet formulation with a specific particle size range for glibenclamide, to range from 2 urn to 60 um (at most 10% can less than 2 urn and at most 10% can more than 60 um).
It is desired that the bioavailability of each of the molecule (in combination) should be similar, if not improved, to individual molecule if administered alone.

Objective of the invention; -
An object of the invention is to prepare tablets comprising a combination of antidiabetics (eg. Metformin and glibenclamide) in multi strength combinations.

Detailed description of the invention: -
The present invention provides stable formulae for tablets comprising antidiabetic drug combination (eg. Metformin and glibenclamide) in three different therapeutically recommended strengths i.e. 500:5, 500:2.5, 250:1.25 mg.
Metformin is used as Metformin hydrochloride. Glibenclamide having different particle size is used for tablet preparation. The other excipients used to prepare tablets are diluents, binders, lubricants, glidants, disintegrants, a surfactant and coating agent.
In the first embodiment, the particle size distribution of Glibenclamide lies in the range, 0.2 urn to 10 um (i.e. more than 30% of particles are less than 2 um and 100% at 10 urn).
In the second embodiment, the particle size distribution lies in the range, 0.4 um to 210 um (i.e. more than 30% of particles are bigger than 60 um).
In this experiment, different ingredients are used as per below mentioned range, in table I

TABLE I

Ingredients Range
Diluents 10 to 15%
Binder 4 to 6 %
Disintegrant 3 to 5 %
Surfactant 0 to 1.5%
Lubricant & glidant 1 to 3 %
Coating agent 2 to 3 %
A set of illustrative formulations are given in table II
TABLE II

Amount of ingredient, mg per tablet
PRODUCT IDENTITY 500:5 500:2.5 250:1.25
Ingredients
Metformin hydrochloride 500 500 250
Glibenclamide** 5 2.5 1.25
Microcrystalline cellulose 45.5 48 24
Pregelatinised starch 20 20 10
Cross Carmellose sodium 27.5 27.5 13.75
Polyvinyl Pyrrolidone K 90 15 15 7.5

Sodium lauryl sulfate 2 2 1
Colloidal silicon dioxide 7.5 7.5 3.75
Purified talc 3 3 1.5
Avicel 200 10 10 5
Magnesium stearate 2 2 1
Film coat 15 15 7.5
** Particle size of glibenclamide: - 30% of particles are less than 2 ^m and 100% at 10 ^m
The tablets are prepared by a process comprising:
Ø Geometrical mixing of metformin HCl, glibenclamide, diluents, and surfactant to get uniform mixing.
Ø Forming granules by wet granulation of the above mixture.
Ø Drying the granules in preheated fluidized bed dryer or in tray dryer, by keeping require moisture content in the granules.
Ø Blending the granules with lubricant and glidants.
Ø Compressing of blend to tablets.
Ø Film coating of tablets.

In the present invention efforts are made to obtain drug release from the tablets (all three strengths) imitate the release of drug from the relevant doses of the two single entity formulations are co administered.