枸橼酸西地那非掩味树脂复合物的制备及评价  

Preparation and evaluation of taste-masked sildenafil citrate resin complex

作　　者：张珊[1] 董阳雨 韩晓鹏[1] 秦超[1] 尹莉芳[1] ZHANG Shan;DONG Yang-yu;HAN Xiao-peng;QIN Chao;YIN Li-fang(Department of Pharmaceuties,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学药剂学教研室,南京211198

出　　处：《中国新药杂志》2018年第17期1985-1993,共9页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项资助项目(2014ZX09507004-001;2014ZX09507004-002)

摘　　要：目的:本研究通过离子交换树脂技术对枸橼酸西地那非进行掩味,并对所制备的掩味树脂复合物进行评价。方法:以载药量和药物利用率为指标,采用单因素试验筛选出最优处方工艺,然后采用扫描电子显微镜(scanning electron microscopy,SEM)等分析方法对最优处方的树脂复合物进行结构表征,通过体外溶出度试验研究其释药行为,并评价了树脂复合物的掩味效果。结果:确定的最优处方如下:离子交换树脂为Amberlite IRP-88,药物浓度为15 mg·mL^(-1),药物与树脂质量比为2∶1,制备温度为室温(25℃);SEM等结果表明,药物树脂复合物的形成改变了药物原有的结晶状态;释药机制研究结果表明,其体外释药动力学过程可用Viswanathan方程描述,属于粒扩散过程控制,溶出介质的离子种类会影响药物释放过程;健康志愿者口感评价结果表明,离子交换树脂技术可以有效掩盖药物不良口感,提高患者依从性。Objective： To prepare ion exchange resin complexes for masking the bitter taste of sildenafil citrate,and evaluate the prepared complexes. Methods： The key factors influencing the drug loading and drug availability of sildenafil citrate in the resin complexes were investigated by single-factor tests. Based on single-factor experiments,the optimal preparation conditions were determined. Results： The optimum preparation process was as follows： using Amberlite IRP-88 as the drug carriers,the drug concentration of 15 mg·m L-1,the ratio of drug and resin（ 2∶ 1）,the preparation temperature（ 25 ℃）,and the preparation time（ 6 h）. Drug resin complexes were evaluated by scanning electron microscopy（ SEM）,X-ray diffraction（ XRD） and differential scanning calorimetry（ DSC）. The results showed that the drug resin complexes change the original crystalline state of the drug. The mechanism of release in vitro was controlled by particle diffusion process according to Viswanathan equation. The drug release profiles were influenced by the type of exchange ion of the dissolution media. The results of taste evaluation of healthy volunteers showed that the resin complexes could effectively mask the bitter taste of the drug and improve the patient＇s compliance. Conclusion： The taste-masked sildenafil citrate resin complex has been prepared; it can mask the bitter taste effectively.

关 键 词：枸橼酸西地那非 离子交换树脂 药物树脂复合物 掩味 溶出度 

分 类 号：R944[医药卫生—药剂学]