基于质量源于设计理念结合模糊层次分析法-熵权法优化羟丙甲基纤维素改善栀子水提物可压性研究

Improving compactibility of Gardeniae Fructus extract by HPMC based on systematic optimization with QbD concept and FAHP-entropy weight method

目的探究改性工艺及参数对栀子水提物可压性的影响,并对工艺进行优化。方法以羟丙甲基纤维素(HPMC E2)为改性剂,考察流化包裹、共喷雾干燥、高剪切等粒子修饰技术对栀子水提物可压性的影响,筛选修饰技术;基于质量源于设计(quality by design,QbD)理念结合模糊层次分析法(fuzzy analytics hierarchy process,FAHP)-熵权法对关键质量属性进行综合赋权得到总评归一值(overall desirability,OD),以其作为评价指标对改性工艺参数进行优化设计。结果相比于其他修饰技术,流化包裹改性效果最佳,可显著改善栀子水提物压缩成型性和流动性;工艺参数影响研究结果显示,OD值与进风温度和进料速度呈正相关,与改性剂质量浓度呈负相关,各因素影响程度顺序为进风温度>进料速度>改性剂质量浓度;单因素与响应面优化得到的最佳参数为进风温度70℃,进料速度11 r/min,改性剂质量浓度12%,最优条件所得实测值与预测值RSD<5%;经过系统优化后栀子水提物片剂抗张强度>2 MPa、休止角<40°,达到片剂生产要求。结论改性工艺和工艺参数对可压性改善效果有显著影响,且优选的改性工艺具有较好的可行性和可靠性,为可压性差的中药片剂的工业化生产提供参考依据。

Objective To investigate the effects of the modification technique and process parameters on the compactibility of Gardeniae Fructus extract,and optimizate the detailed process parameters.Methods Hydroxypropyl methylcellulose(HPMC E2)was adopted as the modifier to explore the performance of different modification techniques on the compactibility of Gardeniae Fructus extract such as fluidized coating,spray drying and high shear,etc,and screened out the most suitable modification techniques.The overall desirability(OD)was obtained by comprehensively weighted the critical quality attributes based on the concept of quality by design(QbD)combined with fuzzy analytics hierarchy process(FAHP)-entropy weighting method,and the obtained OD was adopted for optimization the modification process parameters.Results Among the three modification methods,fluidized coating method show the best modification effect with the obviously improved compactibility and fluidity;The OD value was positively correlated with inlet air temperature and feeding rate,and negatively correlated with modifier concentration,and the detailed order of different process parameters on the OD value as follows:air inlet temperature>feeding rate>modifier concentration;After optimization by single factor experiment and response surface method,the optimized condition were as follows:air inlet temperature of 70℃,feeding rate of 11 r/min,modifier concentration of 12%,with the RSD between measured and predicted value less than 5%.After optimization,the tensile strength(>2 MPa)and flowability(<40°)of the Gardeniae Fructus extract tablets met the requirements of tablet production.Conclusion The modification technique and process parameters had a significant effect for improving the compactibility of extracts,and the preferred techniques owned the excellent feasibility and reliability,which provided a reference basis for the industrial production of Chinese medicine tablets with poor compactibility.