当归破壁粉制备工艺优化及物理指纹图谱评价研究

Optimization of preparation process and evaluation of physical fingerprint of Angelicae Sinensis Radix cellwall broken powder

目的优选当归破壁粉的制备工艺,并进行质量评价。方法建立当归中5种活性成分阿魏酸、洋川芎内酯I、阿魏酸松柏酯、藁本内酯和丁烯基苯酞的HPLC测定方法;采用Box-Behnken响应面设计法对粉碎时间、粉碎温度和投料量进行考察,以当归破壁粉的粒径分布(D90,累计粒度分布数达到90%时所对应的粒径)和5种活性成分含量值作为响应值来构建响应面模型,在D90<45μm前提下,对5种活性成分含量做最大值求算,确定最优的当归破壁粉制备工艺参数;以D90、不均匀系数、粒径分布宽度、松装密度、振实密度、颗粒间孔隙度、卡尔指数、比表面积、孔体积、豪斯纳比、休止角、干燥失重和吸湿性13个物理指标构建当归破壁粉的物理指纹图谱,评价最优工艺制备的3批当归破壁粉的相似度。结果5种活性成分HPLC测定方法的精密度、重复性和稳定性等方法学考察结果符合指导原则要求。Box-Behnken响应面优选的工艺参数为粉碎时间35 min、粉碎温度−10℃,投料量580 g。最优工艺制备的3批当归破壁粉5种活性成分含量和响应面拟合结果之间的RSD值均小于3%,物理指纹图谱相似度均在0.994以上。结论Box-Behnken优选的当归破壁粉制备工艺方法在保留活性成分尤其是挥发性成分含量方面具有明显优势,物理指纹图谱作为评价中药粉体物理属性质量一致性的工具有较好的实际效果,两者结合应用有助于实现更高的中药破壁粉生产质量控制水平。

Objective To optimize the preparation process of Angelicae Sinensis Radix cellwall broken powder(ASR CBP)and evaluate the physical quality of powder.Methods A HPLC method was established for the determination of five active constituents(ferulic acid,senkyunolide I,coniferyl ferulate,ligustilide and n-butylidenephthalide)of ASR.The Box-Behnken response surface design method was used.The pulverization time,pulverization temperature and sampling capacity in the pulverization process were investigated.The particle size distribution(D90)of the broken wall powder of ASR and the five active ingredients content were used as the response value to construct the response surface model.Under the premise of D90<45μm,the maximum value of the five active ingredients was calculated to optimize the superfine grinding process parameters.A total of 13 physical indicators of D90,coefficient of nonuniformity,particle size distribution width,bulk density,tap density,interparticle porosity,Karl index,specific surface area,pore volume,Hausner ratio,angle of repose,loss on drying and hygroscopicity were used to establish the physical fingerprint of ASR CBP.The similarity evaluation method was used to evaluate the similarity of different batches of ASR CBP.Results The methodological results of the HPLC method for the determination of the five active ingredients were in accordance with the guidelines.Results of response surface method showed the optimized preparing parameters of ASR CBP technology as follows:35 min of pulverization time,−10℃of pulverization temperature,and 580 g of sampling capacity.The RSD values between the content and the response surface fitting results of five active ingredients of three batches of cellwall broken powder prepared by the optimal process were all less than 3%.The similarity of the three batches of the optimal process of ASR CBP was above 99.4%.Conclusion Box-Behnken optimized preparation method of ASR CBP has obvious advantages in retaining the content of active ingredients,especially volatile components.Physical fingerprinting has good practical effects as a tool to evaluate the consistency of physical properties of Chinese material medica powder.The combination of applications helps to achieve a higher quality control level of Chinese medicine cellwall broken powder production.