反溶剂共沉淀技术制备氟苯尼考固体分散体

本文旨在通过制备氟苯尼考无定形固体分散体（amorphous solid dispersion，ASD）提高其溶解度和生物利用度。选用醋酸羟丙基甲基纤维素琥珀酸酯（hydroxypropyl methyl cellulose acetate succinate，HPMCAS-MF）为载体，利用反溶剂共沉淀法制备氟苯尼考无定形固体分散体，利用X-射线衍射、热分析及扫描电镜对ASD进行表征，并通过测定溶出度和药物代谢动力学对其体内外释药进行研究。结果显示，当氟苯尼考与载体的比例为5：5时形成固体分散体，该固体分散体无氟苯尼考的晶体衍射峰，无氟苯尼考的特定熔点峰，扫描电镜结果未见氟苯尼考ASD表面光滑的晶体形态，而是显示疏松多孔结构，表面积增大，且使氟苯尼考的饱和溶解度提高了4.8倍，相对生物利用度提高了约37.2%，该固体分散体在3个月内稳定性良好。综上表明，利用共沉淀法制备的新型氟苯尼考固体分散体稳定性良好，可有效提高氟苯尼考溶解度和生物利用度。

Preparation of Florfenicol Solid Dispersion by Antisolvent Co-precipitation Technology

This article aims to prepare florfenicol amorphous solid dispersion (ASD) to improve its solubility and bioavailability. The florfenicol ASD was prepared by antisolvent coprecipitation method with hydroxypropyl methyl cellulose acetate succinate (HPMCAS-MF) as carrier. The ASD was characterized by X-ray diffraction, thermal analysis and scanning electron microscopy. The in vitro and in vivo release of florfenicol was studied by dissolution and pharmacokinetics. When the ratio of florfenicol to carrier was 5:5, a solid dispersion was formed. The results showed that there was no crystal diffraction peak of florfenicol and no specific melting point peak of florfenicol. The SEM results showed that the surface of florfenicol ASD was loose and porous, and increased the surface area, and the saturated solubility of florfenicol increased by 4.8 times, and the relative bioavailability increased by 37.2%, and no drug crystal peak appeared in the solid dispersion within 3 months. The results showed that the new solid dispersion of florfenicol prepared by co-precipitation method has good stability and could effectively improve the solubility and bioavailability of florfenicol.