非洛地平固体分散体及其缓释片的制备与体外溶出 - 第三军医大学学报.doc

非洛地平固体分散体及其缓释片的制备与体外溶出度研究 丁晓莉1*，朱玉莲1，任远志1，黄华1#（1.重庆医科大学，重庆400016） 摘要 目的：制备非洛地平固体分散体及其缓释片，并研究其体外溶出度；方法：以聚乙烯吡咯烷酮为载体，采用溶剂法制备非洛地平固体分散体，比较非洛地平原料药，非洛地平与载体不同比例的物理混合物和固体分散体的溶出度；采用差示扫描量热法对分散体进行物相鉴别；以固体分散体为中间体进一步制备非洛地平缓释片，考察自制品与市售在不同介质（水，pH1.0盐酸溶液，pH4.5醋酸盐缓冲液，pH6.8磷酸盐缓冲液，1%吐温-80溶液）中的释放曲线。结果：与非洛地平原料药、非洛地平物理混合物比较，非洛地平固体分散体中药物的溶出度均有提高，且载体比例越大，药物溶出越快，药物与载体比例为1︰6时，30min内药物累积释放度达0%，为原料药的1倍，但药物与载体比例达1︰6以上时，溶出度增加不再明显；自制品与市售品的体外溶出曲线相似因子均大于50%。结论：制备非洛地平固体分散体可提高其体外溶出度，制备的缓释片与市售品的体外释放行为基本相同。 关键词 非洛地平；固体分散体；缓释片；体外溶出度；相似因子 Preparation and Dissolution in vitro of Felodopine Solid Dispersion and Sustained-release Tablets DING Xiao-li1*， ZHU Yu-lian1，REN Yuanzhi1，HUANG Hua1# (Chongqing Medical University ，Chongqing 400016) ABSTRCT OBJECTIVE： To prepare Felodipine solid dispersion(SD) and sustained-release tabletsand to study its dissolution in vitro ；METHOD：Using PVP K29/32 as carrierthe Felodipine SD was prepared by solvent method. The dissolution rates of Felodipine， Felodipne-carrier physical mixture and Felodipine carrier solid dispersion were determined. Powder differential scanning calorimetry(DSC) were used to examine the physical and chemical characteristics of the solid dispersions；Using Felodipine SD as intermediates to prepare sustained-release tablets. The in vitro release behaviors of the self-made products and commercial sustained-release tablets (Plendil) in five kinds of release medium：water， pH1.2 HCL pH4.5 acetic-ammonium acetate buffer， pH6.8 phosphate buffer and 1% Tween-80 solution were investigated. RESULTS： The solubility of Felodipine in Felodipine SD was increased in some extend， compared with raw material and Felodipine-carrier physical mixture. The higher the proportion of carrier was， the rapider the drug dissolved，when the ratio of drug and carrier was 1︰6 the drug dissolution was 80% which is 15 times of that of raw material. When the ratio of drug and carrier was above 1︰6 the increase of dissolution was no longer significant； The f2 values of the self-made pr