Sustained release formulation containing captopril and method

• US 5,433,951 A
• Filed: 10/13/1993
• Issued: 07/18/1995
• Est. Priority Date: 10/13/1993
• Status: Expired due to Fees

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Fakes, Michael G., Serajuddin, Abu T. M.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Kulkosky, Peter F.
• Application Number:
  US08/136,436
• Time in Patent Office: 643 Days
• Field of Search: 424/486, 424/501, 424/502, 424/497, 424/468, 424/502
• US Class Current: 424/486
• CPC Class Codes: A61K 31/401 Proline; Derivatives thereof, e.g. captopril
• CPC Class Codes: A61K 38/556 Angiotensin converting enzyme inhibitors
• CPC Class Codes: A61K 9/4858 Organic compounds

Abstract

A sustained release captopril formulation is provided which is in the form of a capsule containing captopril in a semi-solid matrix of at least one fatty acid glyceride and/or polyethylene glycol ester. A method of preparing such a formulation is also provided.

Claims

1. A sustained release once-a-day oral captopril formulation comprising a therapeutically effective amount of captopril and a non-aqueous semisolid matrix therefor to impart sustained release properties to the captopril, wherein the non-aqueous semisolid matrix is a fatty acid glyceride and/or a polyethylene glycol ester of a fatty acid.

2. The formulation as defined in claim 1 wherein the semisolid matrix is a long chain fatty acid glyceride and/or a polyethylene glycol ester of a long chain fatty acid.

3. The formulation as defined in claim 2 wherein the semisolid matrix is one or a mixture of long chain (C₁₂ to C₁₈) fatty acid glycerides and/or polyethylene glycol esters of (C₁₂ to C₁₈) fatty acids.

4. The formulation as defined in claim 3 wherein the semisolid matrix is a mixture of mono-, di- and/or triglycerides of C₁₂ to C₁₈ fatty acids and/or monoesters and/or diesters of polyethylene glycols of C₁₂ to C₁₈ fatty acids.

5. The formulation as defined in claim 4 wherein the semisolid matrix has a melting point within the range of from about 33°

to about 64°

C. and a hydrophilic/lipophilic value (HLB) of within the range of from about 1 to about 14.

6. The formulation as defined in, claim 5 wherein the semisolid matrix has a melting point of from about 35 to about 55 and an HLB value of from about 7 to about 14.

7. The formulation as defined in claim 6 wherein the semisolid matrix has a melting point of from about 44°

to about 53°

C. and an HLB value of from about 10 to about 14.

8. The formulation as defined in claim 7 wherein the semisolid matrix has a melting point of about 50°

C. and an HLB value of about 13, a melting point of about 53°

C. and an HLB value of about 10 or is a combination of two semisolid matrices having a melting point of about 53°

C. and an HLB value of about 10 and a melting point of about 44°

C. and an HLB value of about 14.

9. The formulation as defined in claim 1 which is administered once daily.

10. The formulation as defined in claim 1 wherein the fatty acid glyceride is a medium chain fatty acid glyceride.

11. The formulation as defined in claim 1 wherein the captopril is present in a weight ratio to the semisolid matrix within the range of from about 0.02:

1 to about 1;

1.

12. The formulation as defined in claim 1 in the form of a capsule filled with captopril and a semisolid matrix.

13. The formulation as defined in claim 1 in the form of a tablet or as beadlets contained in a capsule.

14. A once-a-day oral captopril formulation comprising a therapeutically effective amount of captopril and a semisolid matrix which is one or a mixture of long chain fatty acid glycerides and/or one or a mixture of polyethylene glycol esters of long chain fatty acids.

15. The once-a-day captopril formulation as defined in claim 14 wherein the semisolid matrix is a C₁₂ to C₁₈ fatty acid glyceride and/or a C₁₂ to C₁₈ fatty acid ester of a polyethylene glycol.

16. The once-a-day captopril formulation as defined in claim 15 wherein the C₁₂ to C₁₈ fatty acid glyceride is a mixture of mono- di- and/or triglycerides and/or a mixture of monoesters and/or diesters of polyethylene glycol and a long chain fatty acid, said mixture having a melting point within the range of from about 33°

to about 64°

C. and a hydrophilic/lipophilic balance (HLB) value of within the range of from abut 1 to about 14.

17. A method for forming a once-a-day oral captopril formulation, which comprises mixing captopril and a fatty acid glyceride and/or a fatty acid ester of a polyethylene glycol and forming the mixture into a solid dosage form.

18. The method as defined in claim 17 wherein the fatty acid glyceride is a mixture of mono-, di- and/or triglycerides and/or monoesters and/or diesters of polyethylene glycol and a long chain fatty acid, said mixture having a melting point within the range of from about 33°

to about 64°

C. and a hydrophilic/lipophilic balance (HLB) value of within the range of from about 1 to about 14.