洛伐他汀渗透泵片的制备及体外释药影响因素的考察

Lovastatin osmotic pump tablets:preparation and drug release behaviors in vitro

目的:制备洛伐他汀渗透泵片,考察片芯组成和包衣膜对药物释放行为的影响,并对处方进行优化。方法:根据不同时间药物累积释放度描述药物的释放行为,采用相异因子(f_1)、相似因子(f_2)法评价释放曲线的相似性,利用双因素的复合析因设计优化处方。结果:片芯组成(如聚氧乙烯的相对分子质量及用量,渗透压促进剂种类和增溶剂种类)和包衣膜组成(如聚乙二醇的相对分子质量及用量和衣膜增重)对洛伐他汀渗透泵片的体外释药行为有显著影响。依据最优处方制备的洛伐他汀渗透泵片符合以渗透压差为释药动力的释药模式,1～8h内呈现良好的零级释放特征(r=0．9968),其体外释药曲线与同类进口片在24h内释药行为相似(f_1=10．2,f_2= 79．5)。结论:经优化后制备的洛伐他汀渗透泵制剂释药完全,零级释放特征显著,与同类进口片释药行为相似。

Objective： To investigate optimal formulation and drug release profile of lovastatin osmotic pump tablets. Methods： The optimal formulation and drug release features were studied based on the accumulative drug release rate at different timepoints, heterogeneous factor（f1 ）and homogenous factor （f2）. Results： The major factors to influence the drug release profile in vitro included components of the core tablet, i.e. , PEO relative molecular weight and amount and types of osmotic promoting agent and solubilizer selected, and the selection of coating components, e. g. , PEG molecular weight and amount and the weight of the coating components used. The optimal in vitro drug release profiles obeyed the zeroorder release model within 1 ～ 8 hour （r = 0. 996 8） , which were coincident with the drug release profile the imported lovastatin osmotic pump tablets has （f1 = 10. 2, f2= 79.5）. Conclusion ： The lovatatin osmotic pump tablets were attainable.