基于关键质量属性的L18-Hunter设计法优化穿心莲颗粒干法制粒处方与工艺

Optimization of Dry Granulation Formulation and Process of Andrographis Herba Granules by L18-Hunter Design Based on Critical Quality Attributes

目的:考察干法制粒处方和工艺参数对穿心莲颗粒关键质量属性的影响,确定最优工艺条件。方法:采用L18-Hunter试验设计,考察了填充剂种类、用量,干法制粒工艺参数送料速度、滚轮转速和滚轮压力对颗粒一次成型率、溶化性和脆碎度影响,并优化了干法制粒条件。结果:影响颗粒一次成型率的关键参数为填充剂种类、送料速度和滚轮压力;影响溶化性的关键参数为填充剂用量和送料速度;影响颗粒脆碎度的关键参数为填充剂种类和滚轮压力。最优的制粒处方和工艺条件为:采用40%的乳糖为填充剂,送料速度为50 r/min、滚轮转速为6 r/min、滚轮压力为12 MPa,验证试验结果表明模型具有较高的精确度和预测能力。结论:采用L18-Hunter试验设计优化穿心莲颗粒干法制粒具有较好的可行性,模型预测能力强。研究提升了对干法制粒的理解,为该产品的产业化发展提供了技术和理论支持。

Objective ：To explore the effect of the formulation and process conditions on the critical quality attributes of Androgra- phis Herba granules, and to determine the optinmm process condition for dry granulation. Methods ： Type and amount of fillers, the process parameters of dry granulation such as feeding rate, rolling wheel rate and pressure were explored by L18-Hunter design, these variables were screened for their impacts on granules critical quality attributes of shaping rate at one time, dissolution time and friability. Moreover,the parameters dry granulation were optimized and validated by the statistical model. Results ：The results of the sta- tistical model showed that type of filler, feeding rate and rolling wheel pressure were the key variables which had significant impact on the shaping rate at one time. The amount of fillers and feeding rate were the significant factors which affected the dissolution time, and the type of fillers and rolling wheel pressure were the most important variables for friability of granule. Furthermore, the optimum parameters were as follows,40% lactose was used as filler, feeding rate at 50 r/min, rolling wheel rate at 6 r/min, the pressure was 12 MPa. Validated experiments showed that the model showed good prediction ability and accuracy. Conclusion：It is feasible to use L18- Hunter design to optimize the dry granulation of Andrographis Herba extract. This study has enhanced the understanding of the dry gran- ulation and provides technical and theoretical support for the industrial development of the product.