title: Effect of milling conditions on solid-state amorphization of glipizide, and characterization and stability of solid forms.
abstract: In this study, the amorphization of glipizide was systematically investigated through high-energy ball milling at different temperatures. The results of solid-state amorphization through milling indicated that glipizide underwent direct crystal-to-glass transformation at 15 and 25°C and crystal-to-glass-to-crystal conversion at 35°C; hence, milling time and temperature had significant effects on the amorphization of glipizide, which should be effectively controlled to obtain totally amorphous glipizide. Solid forms of glipizide were detailedly characterized through analyses of X-ray powder diffraction, morphology, thermal curves, vibrational spectra, and solid-state nuclear magnetic resonance. The physical stability of solid forms was investigated under different levels of relative humidity (RH) at 25°C. Forms I and III are kinetically stable and do not form any new solid-state forms at various RH levels. By contrast, Form II is kinetically unstable, undergoing direct glass-to-crystal transformation when RH levels higher than 32.8%. Therefore, stability investigation indicated that Form II should be stored under relatively dry conditions to prevent rapid crystallization. High temperatures can also induce the solid-state transformation of Form II; the conversion rate increased with increasing temperature.
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Xinnuo
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Analytical &Testing Center, Sichuan University, Chengdu 610064, China.
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ma
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China. Electronic address: lihuilab@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D003460:Crystallization / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D005913:Glipizide / Q000737:chemistry*; D006358:Hot Temperature; D006813:Humidity; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D011208:Powders / Q000737:chemistry; D013816:Thermodynamics; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D011208:Powders; D005913:Glipizide
keywords: Amorphization; Glipizide; Solid forms; Solid-state transformations