Investigation into Surface Effects on the Crystal Nucleation and Growth of Clotrimazole Polymorphs

被引:6
作者
Zhang, Jie [1 ,2 ]
Xu, Meixia [3 ]
Wu, Shuiqing [4 ]
Chen, Zhiguo [1 ]
Luo, Liquan [1 ]
Zi, Taotao [1 ]
Peng, Xucong [1 ]
Yang, Qiusheng [1 ]
Liu, Minzhuo [1 ]
Zeng, Zhihong [1 ]
机构
[1] Changsha Univ, Coll Biol & Chem Engn, Changsha 410022, Peoples R China
[2] China Pharmaceut Univ, Sch Pharm, Dept Pharmaceut, Nanjing 210009, Peoples R China
[3] Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Shandong, Peoples R China
[4] Cent South Univ, Xiangya Hosp 2, Dept Urol, Changsha 410011, Peoples R China
关键词
CRYSTALLIZATION; GLASSES; MELT;
D O I
10.1021/acs.cgd.3c00043
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Molecules at the surface are spatially different compared to those in the bulk and potentially influence crystallization. In this study, surface effects on crystallization behaviors of two clotrimazole (CMZ) polymorphs were inves-tigated. Form 2 of CMZ is favored to nucleate both at the surface and in the bulk. The nucleation rates of CMZ polymorphs at the surface are vastly accelerated by 5-6.5 orders of magnitude compared to their bulk nucleation rates. The surface-accelerating effect on the nucleation rates for Form 2 is relatively stronger than that for Form 1. The surface molecular structure and surface dynamics exhibit a combined effect on the enhancement of surface nucleation. The surface also enhances growth rates of the two polymorphs while exhibiting a greater accelerating effect on Form 1. The growth rates of Form 2 are higher in the bulk, while they show the opposite order at the surface, with Form 1 growing faster. The classical nucleation theory holds true in the present system both at the surface and in the bulk, and the thermodynamic barriers of the two nucleation processes are similar. This study is relevant for understanding the nucleation and growth kinetics of drug polymorphs at the surface.
引用
收藏
页码:3535 / 3543
页数:9
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