Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Sri-Ayutthaya Road, Rajathavee, Bangkok, Thailand.
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Sri-Ayutthaya Road, Rajathavee, Bangkok, Thailand; Center of Excellence in Innovative Drug Delivery and Nanomedicine, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Eur J Pharm Biopharm. 2019 Apr;137:68-76. doi: 10.1016/j.ejpb.2019.02.004. Epub 2019 Feb 12.
The purpose of this study was to evaluate the effect of charge on the in vitro drug performances of clarithromycin nanocrystals. To prepare different charges of nanocrystals, media milling was employed with the use of different stabilizing systems. The uncharged nanocrystals were prepared from poloxamer 407. The negatively and positively charged nanocrystals were stabilized using a combination of poloxamer 407 with sodium lauryl sulfate (SLS) and cetyltrimethylammonium bromide (CTAB), respectively. After production, the particle size of the negatively and positively charged nanocrystals was smaller than that of the uncharged one. The similar particle size of variously charged clarithromycin nanocrystals was selected to determine the in vitro drug performances. Dissolution profiles of the variously charged nanocrystals were similar; however, kinetic saturation solubility profiles were different. The positively charged nanocrystals showed higher mucoadhesiveness than the uncharged and the negatively charged nanocrystals. For drug permeation through NCI-N87 and Caco-2 cell monolayers, both charged nanocrystals showed a higher drug transport than the uncharged nanocrystals. It could be concluded that incorporating charge into clarithromycin nanocrystal formulations affected the particle size reduction process as well as the nanocrystal performances. Therefore, the surface charge is one of the crucial factors for the development of nanocrystal formulations.
本研究旨在评估电荷对克拉霉素纳米晶体体外药物性能的影响。为了制备具有不同电荷的纳米晶体，使用了不同的稳定系统进行介质研磨。未带电的纳米晶体由泊洛沙姆 407 制备。带负电荷和正电荷的纳米晶体分别使用泊洛沙姆 407 与十二烷基硫酸钠（SLS）和十六烷基三甲基溴化铵（CTAB）的组合稳定。生产后，带负电荷和带正电荷的纳米晶体的粒径均小于不带电的纳米晶体。选择各种带电克拉霉素纳米晶体的相似粒径来确定体外药物性能。各种带电纳米晶体的溶解曲线相似；然而，动力学饱和溶解度曲线不同。带正电荷的纳米晶体显示出比不带电和带负电荷的纳米晶体更高的粘膜粘附性。对于通过 NCI-N87 和 Caco-2 细胞单层的药物渗透，两种带电纳米晶体都显示出比不带电纳米晶体更高的药物转运。可以得出结论，将电荷纳入克拉霉素纳米晶体配方会影响粒径减小过程以及纳米晶体性能。因此，表面电荷是纳米晶体配方开发的关键因素之一。
