Box-Behnken响应面法优化芍葛颗粒的干法制粒工艺及质量控制研究

Optimization of dry granulation process for Shaoge Granules using box-behnken response surface methodology and quality control research

关键词:  芍葛颗粒  干法制粒  响应面法  HPLC  质量控制

Key words:  Shaoge Granules  dry granulation  response surface methodology  HPLC  quality control

摘要:

[目的] 优化芍葛颗粒成型工艺，并对其质量控制进行初步研究。[方法] 采用干法制粒方法制备芍葛颗粒，以滚轮压力、送料速度、压片速度为考察因素，以成型率、吸湿率、休止角和溶化率为评价指标，采用Box-Behnken响应面法优化干法制粒工艺；以高效液相色谱（HPLC）法测定芍葛颗粒中葛根素、芍药苷、柚皮苷、1，4-二[4-（葡萄糖氧）苄基]-2-异丁基苹果酸酯的含量。[结果] 最佳条件为滚轮压力为20 kg/cm2、送料速度为31 Hz、压片速度为15 Hz，其成型率为91.83%，表明该工艺制备的颗粒成型率高；3批颗粒的平均临界相对湿度为66.55%，相对标准偏差（RSD）为0.06%；含量测定的结果表明，3批颗粒的指标成分含量均一，质量稳定可控。[结论] Box-Behnken响应面法可用于芍葛颗粒干法制粒工艺的优化，优化后的工艺稳定可行，产品质量可控。

Abstract:

[Objective] To optimize the granulation process of Shaoge Granules and conduct a preliminary study on its quality control. [Methods] Shaoge Granules were prepared by dry granulation method；roller pressure，feeding speed，and pressing speed were used as independent variables；granule yield，moisture absorption rate，angle of repose，and dissolution rate were used as response variables；Box-Behnken response surface methodology was used to optimize the dry granulation process；and the content of puerarin，paeoniflorin，naringin，and 1，4-bis[4-（glucosyloxy）benzyl]-2-isobutylmalate in Shaoge Granules was determined by high-performance liquid chromatography（HPLC）. [Results] The optimal conditions were a roller pressure of 20 kg/cm2，feeding speed of 31 Hz，and pressing speed of 15 Hz，resulting in a granule yield of 91.83%，indicating high granulation efficiency；the average critical relative humidity of the three batches of granules was 66.55%，with an RSD of 0.06%；the content determination results showed that the three batches of granules had uniform content of each index component，with stable and controllable quality. [Conclusion] Box-Behnken response surface methodology can be used to optimize the dry granulation process of Shaoge Granules，and the optimized process is stable and feasible，with controllable product quality.