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氯霉素和磺胺甲噁唑固体分散体的溶出速率增强、体外评价及药物释放动力学研究。

Dissolution rate enhancement, in vitro evaluation and investigation of drug release kinetics of chloramphenicol and sulphamethoxazole solid dispersions.

机构信息

Aston Pharmacy School, Aston University, Birmingham, UK.

出版信息

Drug Dev Ind Pharm. 2013 May;39(5):704-15. doi: 10.3109/03639045.2012.689763. Epub 2012 May 29.

Abstract

Formulation of solid dispersions is one of the effective methods to increase the rate of solubilization and dissolution of poorly soluble drugs. Solid dispersions of chloramphenicol (CP) and sulphamethoxazole (SX) as model drugs were prepared by melt fusion method using polyethylene glycol 8000 (PEG 8000) as an inert carrier. The dissolution rate of CP and SX were rapid from solid dispersions with low drug and high polymer content. Characterization was performed using fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). FTIR analysis for the solid dispersions of CP and SX showed that there was no interaction between PEG 8000 and the drugs. Hyper-DSC studies revealed that CP and SX were converted into an amorphous form when formulated as solid dispersion in PEG 8000. Mathematical analysis of the release kinetics demonstrated that drug release from the various formulations followed different mechanisms. Permeability studies demonstrated that both CP and SX when formulated as solid dispersions showed enhanced permeability across Caco-2 cells and CP can be classified as well-absorbed compound when formulated as solid dispersions.

摘要

固体分散体的形成是提高难溶性药物溶出度和溶解速度的有效方法之一。以聚乙二醇 8000(PEG 8000)为惰性载体,采用熔融共融法制备了氯霉素(CP)和磺胺甲恶唑(SX)的固体分散体作为模型药物。具有低药物和高聚合物含量的固体分散体具有快速的 CP 和 SX 溶解速率。采用傅里叶变换红外光谱(FTIR)、差示扫描量热法(DSC)和扫描电子显微镜(SEM)进行了表征。CP 和 SX 固体分散体的 FTIR 分析表明,PEG 8000 与药物之间没有相互作用。高 DSC 研究表明,CP 和 SX 在 PEG 8000 中形成固体分散体时转化为无定形形式。释放动力学的数学分析表明,各种制剂中药物的释放遵循不同的机制。渗透研究表明,CP 和 SX 制成固体分散体时均可增强穿过 Caco-2 细胞的渗透性,CP 制成固体分散体时可被归类为吸收良好的化合物。

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