泮托拉唑钠肠溶固体分散体的制备及表征

采用溶剂冷冻干燥法制备泮托拉唑钠(1)肠溶固体分散体,并优化其处方工艺。运用鱼骨图分析法结合Plackett-Burman设计(PBD),以在pH 6.8介质中45 min时的累积释放率为考察指标,从肠溶载体溶液pH值、药物与肠溶载体的质量比、肠溶材料与冻干保护剂的质量比、搅拌速度、滤膜吸附作用、混合时间6个因素中筛选出关键因素,再通过Box-Behnken设计(BBD)结合响应面法对关键因素进行优化,确定1肠溶固体分散体的最佳处方工艺。结果表明,药物与肠溶载体的质量比、搅拌速度和混合时间对1肠溶固体分散体的释放行为有显著影响,且最优值分别为1∶4、370 r/min、20 min。红外光谱法、拉曼光谱法和差示扫描量热分析表明,1以无定形形式存在于载体中。基于1肠溶固体分散体的片剂与市售1肠溶片相比,在pH 6.8介质中释放的速度更快、程度更高。

Preparation and Characterization of Pantoprazole Sodium Enteric Solid Dispersion

Pantoprazole sodium(1)enteric solid dispersion was prepared by solvent freeze-drying method.Taking the cumulative release at 45 min in pH 6.8 phosphate buffer as the index,fishbone analysis method combined with Plackett-Burman design(PBD)were adopted to select the key influence factors from six factors,namely pH value of the solution of enteric carrier,mass ratio of drug to enteric carrier,mass ratio of enteric carrier to lyoprotectant,stirring speed,adsorption of filter membrane and mixing time.According to the results,a Box-Behnken design(BBD)with response surface methodology was used for further investigation.The optimal parameters were as follows:the mass ratio of drug to enteric carrier was 1∶4,stirring speed was 370 r/min,and the mixing time was 20 min.The results of infrared spectroscopy,Raman spectroscopy and differential scanning calorimetry showed that the drug existed in an amorphous form in the carrier.The self-made tablets based on the optimal enteric solid dispersion were prepared by direct compression,then the release behavior of the drug from the tablets in pH 6.8 media were investigated with the commercial enteric tablets as the control.The results showed that the self-made tablets exhibited higher rate and extent of drug release.