Granted Patent B2

US 7,785,627 · App. 10/664,803 · Granted Aug 31, 2010

Abstract

Claims (35)

1. A once a day oral pharmaceutical tablet consisting of (a) a core; (b) a primary seal coat; (c) an immediate release pioglitazone coating; and (d) optionally an aesthetic coating wherein:

the core (a) consists of:

(i) a compressed mixture of:

(I) 50-98% of metformin hydrochloride;

(II) 0.1-40% of a binding agent;

(III) 0-20% of an absorption enhancer; and

(IV) 0-5% of a lubricant;

(ii) optionally a secondary seal coat surrounding the compressed mixture; and

(iii) a semipermeable membrane consisting essentially of:

(I) 50-99% of a polymer selected from the group consisting of ethylcellulose, cellulose esters, cellulose diesters, cellulose triesters, cellulose ethers, cellulose ester-ether, cellulose acylate, cellulose diacylate, cellulose triacylate, cellulose acetate, cellulose diacetate, cellulose triacetate, cellulose acetate propionate and cellulose acetate butyrate;

(II) 0-40% of a flux enhancer; and

(III) 0-25% of a plasticizer, said membrane having at least one passageway formed therein for release of the metformin;

the primary seal coat (b) is applied to the semipermeable membrane (iii), does not contain an active pharmaceutical ingredient and rapidly disperses or dissolves in water;

the immediate release pioglitazone coating (c) consists of:

(i) 0.1-20% based upon the total weight of the tablet of pioglitazone hydrochloride;

(ii) 0.1-30% based upon the total weight of the tablet of a binder;

(iii) 0-25% based upon the total weight of the tablet of a pore former; and

(iv) 0-20% based upon the total weight of the tablet of a surfactant;

wherein the immediate release pioglitazone coating (c) is applied to the primary seal coat (b) that is applied to the semipermeable membrane (a)(iii) of the core (a);

the tablet provides a Tmax of 8-12 hours for the metformin and a Tmax of 1-4 hours for the pioglitazone:

the tablet exhibits the following metformin dissolution profile when tested in a USP Type 2 apparatus at 75 rpms in 900 ml of simulated intestinal fluid and 37° C.:

0-15% of the metformin is released after two hours;

20-40% of the metformin is released after four hours;

45-90% of metformin is released after eight hours; and

not less than 60% of the metformin is released after twelve hours; and the tablet exhibits the following pioglitazone dissolution profile when tested in a USP apparatus Type 1 apparatus at 100 rpm in a pH 2.0 HCl-0.3M KCl buffer solution:

at least 79% of the pioglitazone is released after 20 minutes and

at least 95% of the pioglitazone is release after 30 minutes.

2. The tablet of claim 1 wherein the immediate release pioglitazone coating is applied to the primary seal coating using a solvent mixture of water and an organic solvent.

3. The tablet of claim 1 wherein the compressed mixture of the core consists of:

(I) 75-95% of metformin hydrochloride;

(II) 3-15% of a binding agent;

(III) 2-10% of an absorption enhancer; and

(IV) 0.5-1% of a lubricant.

4. The tablet of claim 1 wherein the polymer of the semipermeable membrane is cellulose acetate.

5. The tablet of claim 1 wherein the polymer of the semipermeable membrane is cellulose acetate.

Assignments (8)