马来酸卡比沙明药物树脂复合物的制备优化及评价

摘要

目的 制备马来酸卡比沙明药物树脂复合物,筛选最佳制备条件,并考察其理化性质、药物释放及掩味效果.方法 动态法制备复合物,响应面法优化筛选药液流速、质量浓度及洗脱时间对药物利用率(DA)和树脂载药量(DL)的影响.用差示扫描量热法(DSC)及傅里叶变换红外光谱(FTIR)分析其形成机理,并考察其释放及掩味效果.结果 通过Box-Behnken响应面法进行优化后选择药液质量浓度为7.97 mg·mL -1,药液流速为1.35 mL·min-1,洗脱时间为114.38 min,得到实际药物利用率为85.75%,树脂载药量为1.035 g·g -1.经DSC与FTIR进行理化性质分析表明复合物为无定型态.模拟胃肠道释放实验证明其仅在消化道离子丰富的环境中释放,且苦味实验证明其掩味效果明显.结论 动态法制备药物树脂复合物能够满足实际生产中高药物利用率和高载药量的要求,同时优化的药物树脂复合物掩味效果明显,能提高药物顺应性.%Objective To optimize the process variables in the preparation of carbinomaxine maleate drug resin complex and to evalu-ate the physicochemical properties,drug release and in vivo taste masking effect.Methods Drug resin complex was prepared using column process.The experimental design was conducted to study the effect of drug concentration,drug flow rate and elution time on drug availability(DA)and drug loading efficiency(DL).Physicochemical characterization studies were proceeded including dif-ferential scanning calorimetry(DSC)and Fourier transform infrared spectroscopy(FTIR).Results The optimal reaction conditions included 7.97 mg·mL -1drug concentration and 1.35 mL·min-1drug flow rate and 114.38 min elution time which led to the op-timum DA of 85.75% and DL of 1.035 g·g -1.Physicochemical characterization of DSC and FTIR showed amorphous nature of resinates.Drug release profiles manifested that resinates only got released in an ion-rich environment(stomach or intestine)when taken into the body.In vivo taste evaluation demonstrated a sound taste-masking effect.Conclusion The optimized column process successfully improved the drug availability and the drug loading efficiency.Drug resin complex effectively masked unpleasant taste and improved the patient compliance.