环孢素固体分散体的制备及溶出研究

目的: 提高难溶性药物环孢素(CsA)的溶出速率.方法: 选择聚乙二醇(PEG4000)和聚乙烯吡咯烷酮(PVPK30)两种载体,分别以溶剂熔融法和溶剂法制备CsA固体分散体;建立HPLC法检测固体分散体的体外溶出度,并考察不同载体、不同比例及溶出介质、桨法转速对CsA溶出速率的影响.对溶出度结果用Weibull分布模型进行拟合,计算体外溶出参数T50和Td,并进行方差分析.结果: 使用HPLC法测定CsA的体外溶出量准确、稳定、可靠、载体无干扰.制备成的固体分散体能显著提高CsA的体外溶出速率,PVPK30载体的固体分散体的溶出速率明显快于PEG4000载体的固体分散体.溶出介质对药物溶出没有明显影响.结论: CsA: PVPK30为1: 6的固体分散体具有良好的体外速释作用.

Study on Preparation and Dissolution of Ciclosporin Solid Disperser in vitro

Objective: To enhanced the dissolution of ciclosporin. Method: Solid dispersion systems of CsA in PEG4000 or PVP K30 were prepared in various weight ratios by solvent melting method or solvent evaporation method. A HPLC method for determination of CsA in media was established. The effects of carriers'ratios, different dissolution media and rotational speeds on dissolution rate were studied. T 50 and T d were calculated with Weibull model. Levels of statistical significance were assessed by the method of ANOVA. Result: HPLC method was accurated and reliable and no interference from carriers. The dissolution rates in vitro of CsA solid dispersion as obviously raised, and PVP K30 was a better carrier in increasing the dissolution rate compared with PEG4000.Drug release was not influenced by the used dissolution media. Conclusion: The solid disperser of CsA PVP in the proportion of 1 to 6 showed a obvious rapid release effect in vitro .