Jia Shuyu, Ning Shangqi, Leng Yuting, Jing Qiufang, Xu Zhongyu, Ren Fuzheng
Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Polymers (Basel). 2022 Mar 19;14(6):1241. doi: 10.3390/polym14061241.
Microparticles (MPs) and amorphous solid dispersions (SDs) are effective methods to improve the dissolution of insoluble drugs. However, stability is a concern for these two high-energy systems, resulting from high surface area and amorphous polymorph, respectively. As an amphiphilic polymer, Soluplus (SOL) is usually used as a carrier in SDs. In this study, erlotinib microparticles (ERL MPs) and erlotinib solid dispersions (ERL SDs) were prepared with SOL by bottom-up technology and solvent evaporation. The solid-state properties of ERL MPs and ERL SDs were characterized by Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Scanning Electron Microscopy (SEM). The ERL MPs existed in a metastable crystal form A while the ERL SDs existed in an amorphous state. Fourier transform infrared spectroscopy (FT-IR) showed that there was a hydrogen bond interaction between the N-H group of ERL and the carbonyl group of SOL in ERL MPs and SDs. The dissolution profiles of ERL SDs and ERL MPs were improved significantly. ERL MPs showed better stability than ERL SDs in accelerated stability test. The discrepant stabilizing effects of polymer SOL in two systems may provide effective ideas for solubilization of insoluble drugs and the stability of drugs after recrystallization.
微粒（MPs）和无定形固体分散体（SDs）是提高难溶性药物溶出度的有效方法。然而，由于这两种体系分别具有高比表面积和无定形多晶型，稳定性是它们需要关注的问题。作为一种两亲性聚合物，聚乙烯己内酰胺（SOL）通常用作固体分散体的载体。在本研究中，采用自下而上技术和溶剂蒸发法，以SOL制备了厄洛替尼微粒（ERL MPs）和厄洛替尼固体分散体（ERL SDs）。通过差示扫描量热法（DSC）、粉末X射线衍射（PXRD）和扫描电子显微镜（SEM）对ERL MPs和ERL SDs的固态性质进行了表征。ERL MPs以亚稳晶型A存在，而ERL SDs以无定形状态存在。傅里叶变换红外光谱（FT-IR）表明，在ERL MPs和SDs中，ERL的N-H基团与SOL的羰基之间存在氢键相互作用。ERL SDs和ERL MPs的溶出曲线均有显著改善。在加速稳定性试验中，ERL MPs表现出比ERL SDs更好的稳定性。聚合物SOL在两种体系中不同的稳定作用可能为难溶性药物的增溶和药物重结晶后的稳定性提供有效的思路。
