CONTROLLED RELEASE METFORMIN FORMULATIONS

• US 20110195119A1
• Filed: 03/21/2011
• Published: 08/11/2011
• Est. Priority Date: 03/20/1998
• Status: Active Grant

• Current Assignee: Andrx Labs LLC (Abbvie Incorporated)
• Original Assignee: Andrx Labs LLC (Abbvie Incorporated)
• Inventors: Chou, Joseph, Chen, Chih-Ming, Jan, Steve, Cheng, Xiu Xiu
• Granted Patent: US 8,475,841 B2
• Time in Patent Office: Days
• US Class Current: 424/465
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/282 Organic compounds, e.g. fats
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2886 having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

Sustained release pharmaceutical formulations comprising an antihyperglycemic drug or a pharmaceutically acceptable salt thereof are disclosed. The formulations provide therapeutic plasma levels of the antihyperglycemic drug to a human patient over a 24 hour period after administration.

Claims

1-29. -29. (canceled)

30. A method of treating a human diabetic patient with an oral solid sustained release tablet of metformin hydrochloride, comprising:

administering the sustained release tablet to the human diabetic patient once a day under fed conditions, wherein the sustained release tablet comprises (a) a homogeneous core;

(b) optionally a seal coat surrounding the core and (c) a modified polymeric membrane surrounding the seal coat if present or the core if the seal coat is not present wherein;

the core comprises;

(a)(i) 75-95% metformin hydrochloride based upon the total weight of the core

(a)(ii) 3-15% of a binder based upon the total weight of the core; and

(a)(iii) a lubricant; and

the modified polymeric membrane comprises;

(c)(i) a polymer that controls or sustains the release of the metformin from the core;

(c)(ii) a plasticizer selected from the group consisting of triacetin, acetylated monoglyceride, grape seed oil, olive oil, sesame oil, acetyltributylcitrate, acetyltriethylcitrate, glycerin sorbitol, diethyloxalate, diethylmalate, diethylfumarate, dibutylsuccinate, diethylmalonate, dioctylphthalate, dibutylsebacate, triethylcitrate, tributylcitrate, and glycerlotributyrate;

(c)(iii) a water soluble or enteric flux enhancing agent selected from the group consisting of sodium chloride, potassium chloride, sucrose, sorbitol, mannitol, polyethylene glycol, propylene glycol, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, polyvinyl alcohols, methacrylic acid copolymers and mixtures thereof; and

the metformin is released from the core by a passageway and/or pores in the modified polymeric membrane so that the oral solid sustained release tablet exhibits the following in vitro dissolution profile when tested in a USP Type 2 apparatus at 75 rpms in 900 ml of a pH 7.5 phosphate buffer and 37°

C.;

0-25% of the metformin is released after 2 hours;

10-45% of the metformin is released after 4 hours;

30-90% of the metformin is released after 8 hours;

not less than 50% of the metformin is released after 12 hours;

not less than 60% of the metformin is released after 16 hours and not less than 70% of the metformin is released after 20 hours.

31. The method as defined in claim 30 wherein the oral solid sustained release tablet exhibits the following in vitro dissolution profile when tested in a USP Type 2 apparatus at 75 rpms in 900 ml of a pH 7.5 phosphate buffer and 37°

C.;

0-15% of the metformin is released after 2 hours;

20-40% of the metformin is released after 4 hours;

45-90% of the metformin is released after 8 hours;

not less than 60% of the metformin is released after 12 hours;

not less than 70% of the metformin is released after 16 hours and

not less than 80% of the metformin is released after 20 hours.

32. The method of claim 30 wherein the oral solid sustained release tablet is administered with or after a meal.

33. The method of claim 30 wherein the oral solid sustained release tablet is administered with or after evening meal.

34. The method of claim 30 wherein the polymer of the modified release polymeric membrane is cellulose acetate.

35. The method of claim 30 wherein the oral solid sustained release tablet that does not employ an expanding polymer.

36. A method of treating a human diabetic patient with an oral solid sustained release tablet of metformin hydrochloride, comprising:

administering the sustained release tablet to the human diabetic patient once a day under fed conditions, wherein the sustained release tablet comprises (a) a homogeneous core;

(b) optionally a seal coat surrounding the core and (c) a modified polymeric membrane surrounding the seal coat if present or the core if the seal coat is not present wherein;

the core comprises;

(a)(i) 75-95% metformin hydrochloride based upon the total weight of the core

(a)(ii) 3-15% of a binder based upon the total weight of the core; and

(a)(iii) a lubricant; and

the modified polymeric membrane comprises;

(c)(i) cellulose acetate;

(c)(ii) a plasticizer selected from the group consisting of triacetin, acetylated monoglyceride, grape seed oil, olive oil, sesame oil, acetyltributylcitrate, acetyltriethylcitrate, glycerin sorbitol, diethyloxalate, diethylmalate, diethylfumarate, dibutylsuccinate, diethylmalonate, dioctylphthalate, dibutylsebacate, triethylcitrate, tributylcitrate, and glycerlotributyrate;

(c)(iii) a water soluble or enteric flux enhancing agent selected from the group consisting of sodium chloride, potassium chloride, sucrose, sorbitol, mannitol, polyethylene glycol, propylene glycol, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, polyvinyl alcohols, methacrylic acid copolymers and mixtures thereof; and

the metformin is released from the core by a passageway and/or pores in the modified polymeric membrane so that the oral solid sustained release tablet exhibits the following in vitro dissolution profile when tested in a USP Type 2 apparatus at 75 rpms in 900 ml of a pH 7.5 phosphate buffer and 37°

C.;

0-25% of the metformin is released after 2 hours;

10-45% of the metformin is released after 4 hours;

30-90% of the metformin is released after 8 hours;

not less than 50% of the metformin is released after 12 hours;

not less than 60% of the metformin is released after 16 hours and not less than 70% of the metformin is released after 20 hours.

37. The method as defined in claim 36 wherein the oral solid sustained release tablet exhibits the following in vitro dissolution profile when tested in a USP Type 2 apparatus at 75 rpms in 900 ml of a pH 7.5 phosphate buffer and 37°

C.;

0-15% of the metformin is released after 2 hours;

20-40% of the metformin is released after 4 hours;

45-90% of the metformin is released after 8 hours;

not less than 60% of the metformin is released after 12 hours;

not less than 70% of the metformin is released after 16 hours and

not less than 80% of the metformin is released after 20 hours.

38. The method of claim 36 wherein the oral solid sustained release tablet is administered with or after a meal.

39. The method of claim 36 wherein the oral solid sustained release tablet is administered with or after evening meal.

40. The method of claim 36 wherein the oral solid sustained release tablet that does not employ an expanding polymer.