香青兰总黄酮微丸制备工艺及释药机制研究

Preparation technology of Dracocephalum moldevica total flavonoids pellets and its release mechanism

目的优化香青兰总黄酮微丸制备工艺,初步探讨其释药机制。方法采用Box-Behnken中心组合设计,以挤出速率、滚圆速率、滚圆时间为自变量,收率、脆碎度、圆整度和总评归一化值(OD)为因变量,利用响应曲面法(response surface methodology,RSM)分析自变量对因变量的影响,确定较优条件进行验证试验。通过体外溶出试验考察微丸的累积溶出率,采用扫描电镜技术观察微丸内部结构。结果香青兰总黄酮微丸最佳制备工艺条件:挤出速率36.96 Hz,滚圆速率37.18 Hz,滚圆时间5 min。在此条件下,预测值和测定值偏差绝对值均<4%,与模型拟合程度较高。微丸累积溶出度较好,采用扫描电镜可观察到微丸内部形成骨架结构。结论优化了香青兰总黄酮微丸制备工艺,该方法科学、简便、可行。微丸吸水膨胀崩解的原因是低取代羟丙基纤维素的强溶胀作用。

Objective To optimize the preparation technology of the Dracocephalum moldevica total flavonoids pellets （DMTFP）, and to study its release mechanism. Methods The Box-Behnken central composite design was used, and the extrusion speed, spheronisation speed, and spheronisation time were taken as the independent variables; The yield, friability, sphericity, and general normalized value were taken as dependent variables. The response surface methodology （RSM） was used to estimate the relationship between the dependent and independent variables, and to validate the optimal formulation. Then the dissolution behaviors of DMTFP were investigated by in vitro dissolution test. The internal structure of DMTFP was observed by scanning electron microscopy （SEM）. Results The optimal conditions were as follows： the extrusion speed was 36.96 Hz, the spheronisation speed was 37.18 Hz, and the spheronisation time was 5 rain. Under these conditions, the measured value was consistent with the predicated value with RSD 〈 4 %. The dissolution rate of DMTFP was good, and the internal structure of DMTFP was matrix type by SEM. Conclusion The preparation technology of DMTFP is optimized, which is simple and feasible. The bulge of low-substituted hydroxypropyl cellulose is the reason of disintegration of DMTFP.