Soft-gelatin capsule formulation

• US 8,026,393 B2
• Filed: 01/23/2007
• Issued: 09/27/2011
• Est. Priority Date: 01/24/2006
• Status: Active Grant

• Current Assignee: Sucampo GmbH (Mallinckrodt plc)
• Original Assignee: R-Tech UENO Limited (Mallinckrodt plc), Sucampo AG (Mallinckrodt plc)
• Inventors: Harada, Yasuhiro, Ueno, Ryuji, Hashitera, Yukiko, Hirata, Ryu
• Primary Examiner(s): Sullivan; Daniel
• Assistant Examiner(s): VALENROD, YEVGENY
• Application Number:
  US11/656,476
• Publication Number:
  US 20070172523A1
• Time in Patent Office: 1,708 Days
• Field of Search: None
• US Class Current: 562/504
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 9/4816 Wall or shell material
• CPC Class Codes: A61K 9/4825 Proteins, e.g. gelatin gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention discloses a soft gelatin capsule formulation of a 15-keto-prostaglandin compound, which comprises: a soft gelatin capsule shell comprising gelatin and sugar alcohol as a plasticizer, and a mixture comprising a 15-keto-prostaglandin compound and a pharmaceutically acceptable vehicle which is filled in the shell. By encapsulating the 15-keto-prostaglandin compound in the specified soft gelatin capsule shell, stability of the compound is significantly improved.

Claims

1. A soft gelatin capsule formulation of a 15-keto-prostaglandin compound, which comprises:

a soft gelatin capsule shell comprising gelatin and a sugar alcohol as a plasticizer, and

a mixture comprising a 15-keto-prostaglandin compound and a pharmaceutically acceptable vehicle, which is filled in the shell.

2. The formulation of claim 1, wherein the 15-keto-prostaglandin compound is a compound of the formula (I):

3. The formulation of claim 1, wherein the 15-keto-prostaglandin compound is a 13,14-dihydro-15-keto-prostaglandin compound.

4. The formulation of claim 1, wherein the 15-keto-prostaglandin compound is a 15-keto-16-mono or 16,16-di-halogen-prostaglandin compound.

5. The formulation of claim 1, wherein the 15-keto-prostaglandin compound is a 13,14-dihydro-15-keto-16-mono- or 16,16-di-halogen-prostaglandin compound.

6. The formulation of claim 1, wherein the 15-keto-prostaglandin compound is a 15-keto-16-mono- or 16,16-di-fluoro-prostaglandin compound.

7. The formulation of claim 1, wherein the 15-keto-prostaglandin compound is a 13,14-dihydro-15-keto-16-mono- or 16,16-di-fluoro-prostaglandin compound.

8. The formulation of claim 1, wherein the 15-keto-prostaglandin compound is a 15-keto-prostaglandin E compound.

9. The formulation of claim 1, wherein the 15-keto-prostaglandin compound is a 13,14-dihydro-15-keto-16,16-difluoro-prostaglandin E₁.

10. The formulation of claim 1, wherein the 15-keto-prostaglandin compound is a 13,14-dihydro-15-keto-16,16-difluoro-18S-methyl-prostaglandin E₁.

11. The formulation of claim 1, wherein the sugar alcohol is selected from the group consisting of sorbitol, maltitol, sugar alcohol solution derived from corn starch, hydrogenated maltose syrup and a mixture thereof.

12. The formulation of claim 1, wherein the sugar alcohol comprises sorbitol and sorbitan as its major component.

13. A method for stabilizing a 15-keto-prostaglandin compound, which comprises:

dissolving, dispersing or mixing the 15-keto-prostaglandin in a pharmaceutically acceptable vehicle to give a liquid mixture, and incorporating the liquid mixture in a soft gelatin capsule which comprises gelatin and a sugar alcohol as a plasticizer such that a soft gelatin capsule formulation of claim 1 is prepared.

14. A method for stabilizing a 15-keto-prostaglandin compound, which comprises encapsulating the compound together with a glyceride in a soft gelatin capsule shell comprising gelatin and a sugar alcohol as a plasticizer such that a soft gelatin capsule formulation of claim 1 is prepared.

15. The formulation of claim 1, wherein the pharmaceutically acceptable vehicle is a medium chain fatty acid triglyceride.

16. The method of claim 14, wherein the glyceride is a medium chain fatty acid triglyceride.

17. The formulation of claim 1, wherein the pharmaceutically acceptable vehicle is a fatty acid ester or a polyol.

18. The formulation of claim 1, wherein the pharmaceutically acceptable vehicle is glycerin or propylene glycol.

19. The formulation of claim 1, wherein the pharmaceutically acceptable vehicle is a fatty acid ester or glycerin.

20. The formulation of claim 1, wherein the pharmaceutically acceptable vehicle is a glyceride.

21. The formulation of claim 1, wherein the pharmaceutically acceptable vehicle is a fatty acid ester.

22. The formulation of claim 1, wherein the pharmaceutically acceptable vehicle is glycerin.