蒿甲醚pH依赖型固体分散体处方研究

Study on the Formulation of Artemether p H-Dependent Solid Dispersion

目的:为了提高蒿甲醚的溶出度,通过处方筛选,将蒿甲醚制备成pH依赖型固体分散体。方法:采用喷雾干燥法,以醋酸羟丙甲纤维素琥珀酸酯(HPMCAS-HF)、羟丙基甲基纤维素邻苯二甲酸酯(HP-55)、Eudragit S100为载体,分别制备蒿甲醚固体分散体,以溶出度和稳定性为指标筛选出最佳载体;再用筛选出的最佳载体以不同比例制备蒿甲醚固体分散体,以溶出度为指标筛选出最佳比例。并以粒度检查、电子扫描显微镜(SEM)观察、X射线粉末衍射法分析(XRD)及溶出度测定等,对筛选出的最佳处方进行质量评价。结果:蒿甲醚pH依赖型固体分散体最佳处方为蒿甲醚∶HPMCAS-HF=1∶1,具有较好的pH依赖释药性能和稳定性,质量评价符合设计要求。结论:本方法制备的蒿甲醚固体分散体达到了pH依赖性释药要求,适合制备成结直肠定位释药制剂。

Objective: In order to improve the dissolution of artemether and make the drug release with pH-dependent properties, the best formulation was explored with artemether prepared into a pH-dependent solid dispersion using a carrier material dissolved at specific pH. Methods: Spray drying was used to prepare artemether solid dispersions with hydroxypropyl methylcellulose acetate succinate(HPMCAS-HF),hydroxypropyl methylcellulose phthalate(HP-55) or Eudragit S100, the optimal carrier was selected with the dissolution and stability as indicators;then the optimal carrier was used to prepare the solid dispersion of artemether in a best proportion with the dissolution ratio as the indicator. Particle size examination,scanning electron microscopy(SEM), X-ray powder diffraction analysis(XRD) and dissolution were used to evaluate the quality of the best formulation. Results: The best prescription for artemether pH-dependent solid dispersion was artemether: HPMCAS-HF =1 ∶1, with good pH-dependent drug release properties and stability, and the quality evaluation met the design requirements. Conclusion: The artemether solid dispersion prepared by this method can achieve the requirement of pH-dependent drug release and is suitable for further preparation of colorectal drug delivery preparations.