Development of carrier-free nanocrystals of poorly water-soluble drugs by exploring metastable zone of nucleation

作     者：Xiaoting Ren Jianping Qi Wei Wu Zongning Yin Tonglri Li Yi Lu 

作者机构：Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of Pharmacy Sichuan University Department of Pharmaceutics School of Pharmacy Fudan University Department of Industrial and Physical Pharmacy College of Pharmacy Purdue University 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2019年第9卷第1期

页      面：118-127页

核心收录：

学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the Natural Science Foundation of Shanghai (16ZR1403500) 

主　　题：Nanocrystals Metastable zone Nucleation Sonication Dissolution Paclitaxel 

摘      要：There has been increasing interest in research and development of nanocrystals for the delivery of poorly water-soluble drugs that can be directly produced from solution. Compared with traditional carrier-based or encapsulation designs, drug nanocrystals circumvent possible side-effects due to carrier polymers and poor stability issues associated with encapsulation. The production of carrier-free nanocrystals requires careful control of nucleation and thus a thorough understanding of the relevant solution s metastable zone. A solution may stay supersaturated without forming any nuclei and become metastable. The maximal degree of supersaturation is known as the metastable zone width. When nucleation is triggered directly from the metastable zone, it helps to produce homogeneous nuclei leading to uniform nanocrystals. Herein, we report a study in which the solubility and metastable limit of paclitaxel(PTX) in ethanol aqueous solution were measured at 40 °C. A wide range of metastable compositions were studied to prepare carrier-free PTX nanocrystals with particle size smaller than250 nm and PDI less than 0.25. Compared with the raw material, dissolution rate of PTX nanocrystals was significantly increased. The study enables production of high-quality drug nanocrystals for treating patients.