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J Pharm Biomed Anal. 2016 Sep 10;129:367-377. doi: 10.1016/j.jpba.2016.07.026. Epub 2016 Jul 18.

Effect of milling conditions on solid-state amorphization of glipizide, and characterization and stability of solid forms.

Author information

1
College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
2
Analytical &Testing Center, Sichuan University, Chengdu 610064, China.
3
College of Chemical Engineering, Sichuan University, Chengdu 610065, China. Electronic address: lihuilab@sina.com.

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.

KEYWORDS:

Amorphization; Glipizide; Solid forms; Solid-state transformations

PMID:
27454088
DOI:
10.1016/j.jpba.2016.07.026
[Indexed for MEDLINE]

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