Affiliation:
1. College of Biological and Chemical Engineering, Changsha University, Changsha 410022, China
2. Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
3. Yantai Key Laboratory of Nanomedicine and Advanced Preparations, Yantai Institute of Materia Medica, Shandong 264000, China
Abstract
Clotrimazole (CMZ) is a classical antifungal drug for studying crystallization. In this study, a new CMZ polymorph (Form 2) was discovered during the process of nucleation and growth rate determination in the melt. High-quality single crystals were grown from melt microdroplets to determine the crystal structure by x-ray diffraction. Form 2 is metastable and exhibits a disordered structure. The crystal nucleation and growth kinetics of the two CMZ polymorphs were systematically measured. Form 2 nucleates and grows faster than the existing form (Form 1). The maximum nucleation rate of Forms 1 and 2 was observed at 50 °C (1.07 Tg). The summary of the maximum nucleation rate temperature of CMZ and the other six organic compounds indicates that nucleation near Tg in the supercooled liquid is a useful approach to discovering new polymorphs. This study is relevant for the discovering new drug polymorphs through an understanding of nucleation and growth kinetics during melt crystallization.
Funder
Natural Science Foundation of Hunan Province
Science and Technology Bureau, Changsha
Natural Science Foundation of Jiangsu Province
National Natural Science Foundation of China
Outstanding Youth Fund of Jiangsu Province of China
Program of State Key Laboratory of Natural Medicines-China Pharmaceutical University
Scientific Research Fund of Hunan Provincial Education Department
Key R&D Program of Hunan Province, China
Subject
Physical and Theoretical Chemistry,General Physics and Astronomy
Cited by
2 articles.
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