PHARMACEUTICAL COMPOSITIONS THAT INHIBIT DISPROPORTIONATION

摘要

Pharmaceutical formulations comprising solid pharmaceutically acceptable organic acids, such as maleic acid or tartaric acid, that inhibit the disproportionation of pharmaceutically acceptable acid salts of active pharmaceutical ingredients, and methods of manufacturing such pharmaceutical compositions. The pharmaceutically acceptable acid salt of the active pharmaceutical ingredient has a pKa of less than about 6.0, and wherein the solid pharmaceutically acceptable organic acid has a pKa of less than about 4.0 and an aqueous solubility in the range of about 500 to about 2000 milligrams per milliliter. A pharmaceutical formulation comprising a pharmaceutical acceptable acid salt of pioglitazone, a solid pharmaceutically acceptable organic acid selected from the group consisting of maleic acid or tartaric acid, and an excipient that promotes disproportionation, wherein the ratio by weight of the solid pharmaceutically acceptable organic acid to excipient is from about 1:6 to about 1:1.

主权项

1. A pharmaceutical formulation comprising:
(1) a pharmaceutically acceptable acid salt of an active pharmaceutical ingredient, and (2) a solid pharmaceutically acceptable organic acid in a sufficient amount to reduce disproportionation,
wherein the pharmaceutically acceptable acid salt of the active pharmaceutical ingredient has a pKa of less than about 6.0, andwherein the solid pharmaceutically acceptable organic acid has a pKa of less than about 4.0 and an aqueous solubility in the range of about 500 to about 2000 milligrams per milliliter.