期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 107, 期 1, 页码 121-126出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2017.07.003
关键词
amorphous; calorimetry (DSC); crystal polymorphism; glass; glass transition; materials science; mechanical activation; milling; solid state; X-ray powder diffractometry
资金
- ANR (The French National Research Agency) [ANR-14-CE16-0025-01/02]
In this paper, solid-state amorphization induced by mechanical milling is shown to be a useful tool to explore the polymorphism of drugs and their mechanism of devitrification. We show in particular how the recrystallization of amorphous chlorhexidine dihydrochloride obtained by milling reveals a complex polymorphism that involves several polymorphic forms. Two new crystalline forms are identified, one of them appearing as a highly disordered precursor state which however clearly differs from the amorphous one. Several interpretations are here proposed to describe the puzzling nature of this phase. In addition, the possibility to amorphize chlorhexidine dihydrochloride by milling allowed to determine the main physical characters of the amorphous state which cannot be obtained through the usual thermal quench of the liquid because of a strong chemical degradation occurring on melting. (c) 2018 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
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