Polymorphs and Amorphous State of Glipizide: Preparation and Solid-State Transformations.

Abstract

The solid-state diversity of active pharmaceutical ingredients can provide theoretical guidance for the production and storage of drugs. In this study, three solid forms of glipizide were obtained through various methods, and the solid-state transformations were extensively investigated. Form I could be prepared using evaporative crystallization, cooling crystallization, anti-solvent crystallization, and solvent-mediated slurry conversion experiments (SSCE). Form II was produced by milling. Form III was obtained by milling and SSCE. The results of solid-state transformations indicated that Form I transformed to II during neat milling at 25°C. In contrast, solvent inhibited the solid-state transformations of Form I under liquid-assisted milling. Forms II and III remained invariable under neat milling at 25°C, and solid-state transformation of Form III also did not occur in the liquid-assisted milling. In SSCE, the solvent's nature and its temperature significantly influenced the solid-state conversion of amorphous glipizide. Form II converted to either Form I or III in water above 50°C, and only transformed into Form I at 25°C. However, the solid-state transformation did not occur when pure Form I or III was stirred in water. Form II also converted to Form I in the organic solvents SSCE at different temperatures.