抗甲方颗粒流化床制粒工艺优化及制剂质量评价研究

Study on optimization of fluidized bed granulation process for Anti-Hashimoto’s Thyroiditis Formula Granules and preparation quality evaluation

目的:优化抗甲方颗粒流化床制粒工艺,以提高制剂处方的载药量,进而对获得的颗粒剂开展质量评价研究。方法:以颗粒的制备可行性、成型率、颗粒粒径、流动性为评价指标,对流化床制粒的初始物料温度、进风温度、浓缩液密度进行单因素考察;建立HPLC方法测定颗粒中的毛蕊异黄酮苷和迷迭香酸含量,并采用《中国药典》方法对制剂开展水分、粒度和溶化性等项目检查。结果:优化后的制粒参数为初始物料温度(38±1)℃,进风温度70℃,浓缩液密度为1.24~1.26 g/cm(25℃);制得颗粒载药量为72%,较工艺优化前提高了约50%。所得制剂中毛蕊异黄酮苷和迷迭香酸含量分别为0.298 3 mg/g和0.989 5 mg/g;同时,其水分、粒度和溶化性等检查项目均符合药典要求。结论:本研究所得制剂工艺稳定可行、载药量高,相关的质量研究工作可为进一步制定制剂的质量标准奠定基础。

Objective:The fluidized bed granulation process of anti-Hashimoto’s thyroiditis Formula Granules was optimized to improve the drug loading capacity of the formulation,and then the quality evaluation of the obtained granules was carried out accordingly.Methods:Taking preparation feasibility,forming rate,particle size and fluidity of granules as evaluation indexes,the initial material temperature,inlet air temperature and concentrated solution density of fluidized bed granulation were investigated by single factor experiment. HPLC method was established for content determination of calycosin-7-O-β-D-glucoside and rosmarinic acid in the granules,and the moisture,particle size and solubility of the granules were examined by Chinese Pharmacopoeia’s methods.Results:The optimized granulation parameters were as follows:initial material temperature(38±1)℃,air inlet temperature 70℃,concentrated liquid density was1.24~1.26 g/cm~3(25 ℃). The drug loading of the obtained granules was 72%,which was about 50% higher than that before optimization.The contents of calycosin-7-O-β-D-glucoside and rosmarinic acid in the obtained preparation were 0.298 3 mg/g and 0.989 5 mg/g,respectively. Meanwhile,its moisture,particle size and solubility and other inspection items all met the requirements of Chinese Pharmacopoeia.Conclusion:The preparation process obtained in this study is stable and feasible,and the drug loading capacity is high.The related quality research can lay a foundation for further formulation of quality standard of the preparation.