微粉化增溶技术在残黄片工艺中的应用

Application of Ultrafine Powder Solubilization Technology in Process of Canhuang Tablets

目的:考察微粉化残黄片的体外溶出度及退黄药效作用,优选微粉化残黄片的超微粉粒度。方法:以小檗碱为指标,采用HPLC测定不同粉碎粒度的微粉残黄片在不同时间段的小檗碱溶出量,计算累计溶出度,观察溶出情况;采用4%ANIT造成大鼠高黄疸模型,按给药方案给药,股动脉取血,测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)、直接胆红素(DBIL)、谷氨酰转肽酶(γ-GT)等血清生化指标,评价不同粉碎粒度的微粉残黄片的退黄效果。以体外溶出及退黄效果综合优选微粉化残黄片的超微粉粒度。结果:随粉碎目数的增加,黄连中小檗碱的累计溶出率增加,200目和300目60 min时累计溶出率可分别达94.86%,96.18%;在退黄效果方面,200目残黄片可显著降低ALT,AST和γ-GT,且作用强于100,150,300目的残黄片,在降低ALT和γ-GT作用上甚至优于对照药熊去氧胆酸片。综合残黄片的外观性状及生产实际,确定最佳微粉粒度200目。结论:以体外溶出及退黄效果综合优选微粉化残黄片的超微粉粒度是一种简便、可行的试验设计方法,可推广应用。

Objective： To optimize particle size of ultrafine powder by investigating in vitro dissolution and receding jaundice effect of micronized Canhuang tablets（MCHP）.Method： With berberine as index,release of berberine from MCHP with different crush size in different time periods was determined by HPLC,calculated cumulative dissolution,and then observed dissolution.At the same time,rats jaundice model was caused by 4% ANTI,after administered in accordance with dosing regimen,the femoral artery blood was collected for determining serum biochemical markers,such as ALT,AST,TBIL,DBIL and γ-GT,receding jaundice effect of MCHP with different grinding particle size was evaluated.Superfine powder particle size of MCHP was optimized by Comprehensive evaluating in vitro dissolution and receding jaundice effect.Result： With increasing of pulverized mesh,cumulative dissolution of berberine increased,cumulative dissolution of 200,300 mesh was 94.86%,96.18% at 60 min,respectively.For receding jaundice effect,Canhuang tablets with 200 mesh could significantly reduce ALT,AST and γ-GT,which was stronger than those of Canhuang tablets with 100,150 and 300 mesh,furthermore,that of 200 mesh was superior to control drug ursodeoxycholic acid tablets in reducing ALT and γ-GT.Comprehensive appearance of tablets and actual production,200 mesh was determined as optimum crush size.Conclusion： It was a feasible and convenient method to optimize ultrafine powder particle size of MCHP by combining in vitro dissolution and receding jaundice effect.