Physical property of troglitazone, an equal mixture of four stereoisomers

Troglitazone, an oral antidiabetic agent, is an equal mixture of four stereoisomers involving two chiral centers. In the present study, the physical property of troglitazone were investigated. The solid state of troglitazone drug substance is characterized as a simple physical mixture of two diastereomers, as shown by the two endothermic peaks caused by the melting of the RR/SS and the RS/SR forms by differential scanning calorimetry (DSC). In addition, the powder X-ray diffraction pattern includes peaks resulting from both the RR/SS and the RS/SR forms. The water adsorption of troglitazone drug substance is due to the presence of the RR/SS diastereomer, which adsorbs water as a monohydrate. The solubility of troglitazone and the diastereomers were increased and the solubility ratios of the stereoisomers were changed by quenching. Troglitazone was proved to be stable against heat and humidity by the ratio of the stereoisomers and from the solid state form indicated by the DSC results.