文献类型：期刊文献

中文题名：厄洛替尼固体分散体稳定化载体研究

英文题名：Stabilized Carriers of Erlotinib Amorphous Solid Dispersions

作者：宁尚琦[1];贾舒宇[1];景秋芳[1];任福正[1]

机构：[1]华东理工大学上海市新药设计重点实验室,上海200237

年份：2023

卷号：49

期号：1

起止页码：69

中文期刊名：华东理工大学学报（自然科学版）

外文期刊名：Journal of East China University of Science and Technology

收录：Scopus;北大核心:【北大核心2020】；CSCD:【CSCD_E2023_2024】；

基金：上海市新药设计重点实验室项目(17DZ2271000)。

语种：中文

中文关键词：厄洛替尼;固体分散体;载体;稳定性;羟丙甲基纤维素

外文关键词：erlotinib;solid dispersions;carrier;stability;HPMC

摘要：固体分散体(SDs)是提高难溶性药物溶出度的主要技术之一,它能保持长期物理稳定性的关键是选择合适载体。采用溶剂挥发法,选用6种聚合物为载体,制备厄洛替尼(ERL)SDs;通过Flory-Huggins相互作用参数χ与反溶剂显微观察评估了聚合物与ERL的相容性及对ERL结晶的影响,同时利用聚焦光束反射测量仪(FBRM)在线分析了聚合物对结晶过程的调控作用机制;对不同比例SDs的固态性质进行表征,并测定了样品的无定型状态。结果表明,优选出的羟丙甲基纤维素能长期保持SDs中药物的无定型态,相互作用参数χ计算、反溶剂显微观察及FBRM分析3种方法联合应用有助于快速选择最适载体。
Solid dispersions(SDs) is one of the main technologies to improve the dissolution of poorly soluble drugs in drug research and development. However, supersaturated high-energy amorphous state drug in SDs is often associated with a tendency to recrystallize during long term storage. The carrier of SDs plays a key role in maintaining the amorphous state of the drugs. Traditionally, screening of carrier in the development process is a time-consuming process. The effects of polymer carriers on the long-term physical stability of the amorphous state of Erlotinib(ERL) in SDs were studied. ERL SDs were prepared with different ratios of hydroxypropyl methylcellulose(HPMC),hydroxypropyl methylcellulose acetate succinate(HPMCAS), polyvinylpyrrolidone(PVP), poly(vinylpyrrolidone-covinyl-acetate)(PVP/VA), Eudragit, and Soluplus by solvent evaporation method. On the basis of the Flory-Huggins interaction parameter(χ) and anti-solvent microscopic observations, the compatibility of the polymer with ERL and polymer’s influence on the crystallization of ERL were predicted. Focused Beam Reflectance Measurement(FBRM)system was used to analyze the morphological effect of the polymer on the crystallization process. Then the amorphous state formed by different proportions of SDs were characterized by powder X-ray diffraction(PXRD), differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FT-IR). The physical stability of amorphous state of SDs in accelerated test condition were determined by PXRD. The results indicate that HPMC is a suitable carrier for the preparation of ERL amorphous SDs. The combination of the interaction parameter χ, anti-solvent microscopic observation and FBRM analysis is an effective way for the selection of a suitable carrier for amorphous SDs. The understanding of the impact of polymers on amorphous SDs would be beneficial for the rapid development of poorly soluble drugs.