影响穿心莲颗粒溶出行为的关键颗粒物理特性参数研究

Role of Key Physical Parameters of Andrographis paniculata (Burm. f.) Nees Granules in Their Dissolution Behavior

目的研究颗粒的关键物理特性参数对穿心莲颗粒溶出行为的影响。方法以穿心莲提取物为模型药物,采用不同的工艺分别与微晶纤维素/淀粉按质量比1∶1混合,分别采用摇摆挤压与高速搅拌湿法制粒,后测定颗粒的溶出行为。以脱水穿心莲内酯平衡溶出量与溶出速率常数为指标评价颗粒溶出行为,并采用逐步回归分析方法研究颗粒关键物理特性参数对溶出行为的影响。结果颗粒的粒径、临界相对湿度、含水量、孔体积、密度是影响穿心莲颗粒中脱水穿心莲内酯溶出行为的关键物理特性参数。结论穿心莲颗粒中脱水穿心莲内酯的平衡溶出量与颗粒d50及临界相对湿度呈负相关,与颗粒含水量成正相关;溶出速率常数与颗粒等体积平均径D[4,3]及PV呈负相关,与振实密度成正相关。

OBJECTIVE To establish the relationship between the physical parameters of granules and their dissolution behavior. METHODS Andrographis paniculata （ Burro. f. ） Nees extract was utilized as a model drug. The extract was mixed with different excipients （MCC/soluble starch） at the ratio of 1：1 by weight using different methods. The granules were prepared by using high shear granulation and extrusion granulation methods. Then the dissolution behavior of the granules was evaluated by monitoring equilibrium dissolution quantity and dissolution rate constant. The effect of physical properties on the dissolution behavior was analyzed through stepwise regression. RESULTS Particle size, critical relative humidity （CRH）, moisture content, pore volume, and tapped density were the main factors related to the dissolution behavior of granules. CONCLUSION A higher equilibrium dissolution quantity could be obtained with higher moisture content, smaller particle size, and lower CRH. There is a positive correlation between dissolution rate constant and tapped density of granules, and a negative correlation with particle size （D[4,3] ） and pore volume （PV）.