Salts and Cocrystals of the Antidiabetic Drugs Gliclazide, Tolbutamide, and Glipizide: Solubility Enhancements through Drug–Coformer Interactions

Abstract

Gliclazide (GCZ), tolbutamide (TOL), and glipizide (GPZ) are BCS class II antidiabetic drugs with poor aqueous solubility. Multicomponent solid forms, salts, and cocrystals of GCZ were obtained upon liquid assisted grinding with coformers of catechol, resorcinol, p-toluenesulfonic acid, and piperazine. The solubility of TOL was also modified by salt formation with piperazine (PPZ). The multicomponent solids were characterized by single crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermal gravimetric analysis and further subjected to solubility studies. The cocrystals/salts, in all cases, showed improvements in the solubility and dissolution rates compared to the parent active pharmaceutical ingredients. GCZ–PPZ and TOL–PPZ(I) showed 6.6 and 80 and fold enhancements respectively in the solubility. The reasons for the improved solubility of the cocrystals/salts in terms of drug–coformer interactions are discussed.