Solid-state variation of troglitazone drug substance by using a different recrystallization method.

Abstract

Rapid and slow crystallization methods (A and B) were applied for troglitazone, an equal mixture of four stereoisomers. Differences in the powder x-ray diffractometry patterns and hygroscopic patterns were observed among the samples crystallized by these methods, suggesting that troglitazone has solid-state variation. In this article, troglitazone recrystallized by method A was evaluated to clarify its structural characteristics and physical property. The crystal structure of predried troglitazone recrystallized by method A was proved to be a dihydrate. By drying, it changed reversibly to an anhydrate, which is the same structure as the RS/SR form, keeping the same enantiomer ratio. The solubility of the troglitazone by method A higher than that by method B at all enantiomer levels. But making the troglitazone amorphous equalized the enantiomeric solubilities of the substances by both methods as well as increased the intrinsic solubilities. Troglitazone by both methods was proved to be stable and retained the ratio of the stereoisomers.