伊曲康唑/2-羟丙基环糊精共熔物及其分散片的制备与体外释药考察

Preparation of itraconazole/2-HP-β-CD solid fusion mixture and investigation of in vitro drug release

目的:提高难溶性药物伊曲康唑(ITR)的溶解度和其分散片的制备及溶出度测定。方法:选用2-羟丙基环糊精(2-HP-β-CD)为载体,采用混匀熔融骤冷法制备ITR/2-HP-β-CD共熔物,通过比较考察含相同质量伊曲康唑的原料药、ITR/2-HP-β-CD的物理混合物和其共熔物在水或人工胃液中溶出特征,确定共熔物的处方和工艺的优劣。粉末直接压片法制备其分散片,并通过考察体外释放度确定最佳处方。结果:ITR/2-HP-β-CD共熔物(1∶1)使药物在水和人工胃液中的溶解度增加了120多倍,其分散片在45m in累积释药90%以上。结论:制备的ITR/2-HP-β-CD共熔物增加药物溶解度方法可行。直接压片法制备分散片,方法操作简单,制成的分散片释药特性良好。

OBJECTIVE To prepare itraconazole（ITR）/2-HP-β-CD solid fusion mixture and its dispersible tablets, its pharmaceutical characters and solubility were simultaneously investigated. METHODS The ITR/2-HP-β-CD solid fusion mixture was prepared by melt-cold snap technology. Disperisible tablets were prepared with powder direct compression and pharmaceutical properties were investigated by dissolution test. RESULTS Dissolution measurements demonstrated that a significantly increased dissolution rate obtained with ITR/2-HP-β-CD solid fusion mixture （1 ： 1） was 72. 7 times than that of ITR powder at 45 min The ITR solubility in ITR/2-HP-β-CD solid fusion mixture was 125 times than that of ITR powder. CONCLUSION This prescription and technology of ITR/2-HP-β-CD solid fusion mixture and its dispersible tablets are reasonable and effective.