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两性霉素B球形无定形固体分散体的制备与表征

Preparation and Characterization of Spherical Amorphous Solid Dispersion with Amphotericin B.

作者信息

Mehenni Lyes, Lahiani-Skiba Malika, Ladam Guy, Hallouard François, Skiba Mohamed

机构信息

Normandy UNIV, UNIROUEN, Laboratory of Pharmaceutical & Biopharmaceutical Technology, Inserm U1239, DC2N, UFR of Health, 22 Boulevard Gambetta, 76183 Rouen CEDEX, France.

Normandy UNIV, UNIROUEN, CNRS, PBS (UMR 6270), 55 rue Saint-Germain, 27000 Evreux, France.

出版信息

Pharmaceutics. 2018 Nov 16;10(4):235. doi: 10.3390/pharmaceutics10040235.

Abstract

In the present study, new polymer microspheres of amphotericin B (AmB) were prepared by a spray drying technique using cyclodextrin polymers (Poly-CD) to improve the solubility and dissolution of AmB, to prevent in vivo toxic AmB aggregations. Formulations were characterized through scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermal analysis, Raman spectroscopy, particle size, drug purity test and in vitro release studies. The analysis indicated that the chemical structure of AmB remained unchanged in the amorphous solid dispersion, but the structure was changed from crystalline to amorphous. AmB was completely release from such optimized formulations in dissolution media in 40 min. This work may contribute to a new generation of spherical amorphous solid dispersion using a cyclodextrin polymer, which has implications for the possibility of drug development for oral utilization or as powder aerosols for pulmonary administration.

摘要

在本研究中,采用喷雾干燥技术,使用环糊精聚合物(聚环糊精)制备了新型两性霉素B(AmB)聚合物微球,以提高AmB的溶解度和溶出度,防止体内有毒的AmB聚集。通过扫描电子显微镜(SEM)、傅里叶变换红外光谱(FT-IR)、差示扫描量热法(DSC)、热分析、拉曼光谱、粒径、药物纯度测试和体外释放研究对制剂进行了表征。分析表明,AmB的化学结构在无定形固体分散体中保持不变,但结构从结晶态变为无定形态。在40分钟内,AmB从这种优化制剂中在溶出介质中完全释放。这项工作可能有助于开发新一代使用环糊精聚合物的球形无定形固体分散体,这对于口服利用或作为肺部给药的粉末气雾剂进行药物开发具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/281e/6320868/401b148c6e6a/pharmaceutics-10-00235-g001.jpg

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