Soft-gelatin capsule formulation

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.

Description

Claims

1. A soft gelatin capsule formulation of a 15-keto-prostaglandin compound, which comprises: a soft gelatin capsule shell comprising gelatin and an sugar alcohol as a plasticizer, anda 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 pharmaceutically acceptable vehicle is a fatty acid ester or a polyol.

12. The formulation of claim 1, wherein the fatty acid ester is a glyceride.

13. 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.

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

15. 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.