Mechanically Induced Amorphization of Diaqua-bis(Omeprazolate)-Magnesium Dihydrate
Mechanically Induced Amorphization of Diaqua-bis(Omeprazolate)-Magnesium Dihydrate
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DOI：
10.1021/acs.cgd.0c00770
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发表时间：
2020-09-02
影响因子：
3.8
通讯作者：
Hassanpour, Ali
中科院分区：
文献类型：
--
作者：
Abouhakim, Hanane;Quayle, Michael J.;Hassanpour, Ali
The influence of milling diaqua-bis(omeprazolate)magnesium dihydrate (DABOMD), an active pharmaceutical ingredient (API), was investigated. DABOMD was processed in a planetary ball mill at different milling times, from 1 to 300 min. The milling process resulted in a prominent comminution (size reduction) and amorphization of the API. DABOMD amorphization was identified with various characterization techniques including thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, and attenuated total reflection-Fourier transform infrared spectroscopy. The solid-solid crystalline to amorphous phase transformation is driven by compression, shear stresses, and heat generated in the planetary ball mill. This leads to distortion and breakage of hydrogen bonds, release of water molecules from the crystalline lattice of DABOMD and the accumulation of defects, and eventually a collapse of the crystalline order. Model fitting of the kinetics of comminution and the amorphization of DABOMD revealed a series of events: a rapid comminution at the start of milling driven by crystal cleavage of DABOMD, followed by partial amorphization, which is driven by rapid water diffusion, and subsequently, a slow steady comminution and amorphization.
