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用于提高溶解度和溶出度的阿瑞匹坦磷脂酰胆碱基固体分散体的设计与表征

Design and Characterization of Phosphatidylcholine-Based Solid Dispersions of Aprepitant for Enhanced Solubility and Dissolution.

作者信息

Yeo Sooho, An Jieun, Park Changhee, Kim Dohyun, Lee Jaehwi

机构信息

College of Pharmacy, Chung-Ang University, Seoul 06974, Korea.

出版信息

Pharmaceutics. 2020 Apr 29;12(5):407. doi: 10.3390/pharmaceutics12050407.

Abstract

This study aimed to improve the solubility and dissolution of aprepitant, a drug with poor aqueous solubility, using a phosphatidylcholine (PC)-based solid dispersion system. When fabricating the PC-based solid dispersion, we employed mesoporous microparticles, as an adsorbent, and disintegrants to improve the sticky nature of PC and dissolution of aprepitant, respectively. The solid dispersions were prepared by a solvent evaporation technique and characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry, and X-ray powder diffraction. The FTIR results showed that aprepitant interacted with the PC carrier by both hydrogen bonds and van der Waals forces that can also be observed in the interaction between aprepitant and polymer carriers. The solid dispersions fabricated with only PC were not sufficient to convert the crystallinity of aprepitant to an amorphous state, whereas the formulations that included adsorbent and disintegrant successfully changed that of aprepitant to an amorphous state. Both the solubility and dissolution of aprepitant were considerably enhanced in the PC-based solid dispersions containing adsorbent and disintegrant compared with those of pure aprepitant and polymer-based solid dispersions. Therefore, these results suggest that our PC-based solid dispersion system is a promising alternative to conventional formulations for poorly water-soluble drugs, such as aprepitant.

摘要

本研究旨在利用基于磷脂酰胆碱(PC)的固体分散体系统,提高阿瑞匹坦(一种水溶性差的药物)的溶解度和溶出度。在制备基于PC的固体分散体时,我们分别采用介孔微粒作为吸附剂和崩解剂,以改善PC的粘性和阿瑞匹坦的溶出度。通过溶剂蒸发技术制备固体分散体,并采用傅里叶变换红外光谱(FTIR)、差示扫描量热法和X射线粉末衍射对其进行表征。FTIR结果表明,阿瑞匹坦与PC载体通过氢键和范德华力相互作用,这在阿瑞匹坦与聚合物载体的相互作用中也能观察到。仅用PC制备的固体分散体不足以将阿瑞匹坦的结晶度转变为无定形状态,而包含吸附剂和崩解剂的制剂成功地将阿瑞匹坦的结晶度转变为无定形状态。与纯阿瑞匹坦和基于聚合物的固体分散体相比,在含有吸附剂和崩解剂的基于PC的固体分散体中,阿瑞匹坦的溶解度和溶出度均显著提高。因此,这些结果表明,我们基于PC的固体分散体系统是阿瑞匹坦等水溶性差的药物传统制剂的一种有前景的替代方案。

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