Résumé
The purpose of this study was to investigate the effect of key physical properties of hawthorn leaf granule on its dissolution behavior. Hawthorn leaves extract was utilized as a model drug. The extract was mixed with microcrystalline cellulose or starch with the same ratio by using different methods. Appropriate amount of lubricant and disintegrating agent was added into part of the mixed powder, and then the granules were prepared by using extrusion granulation and high shear granulation. The granules dissolution behavior was evaluated by using equilibrium dissolution quantity and dissolution rate constant of the hypericin as the indicators. Then the effect of physical properties on dissolution behavior was analyzed through the stepwise regression analysis method. The equilibrium dissolution quantity of hypericin and adsorption heat constant in hawthorn leaves were positively correlated with the monolayer adsorption capacity and negatively correlated with the moisture absorption rate constant. The dissolution rate constants were decreased with the increase of Hausner rate, monolayer adsorption capacity and adsorption heat constant, and were increased with the increase of Carr index and specific surface area. Adsorption heat constant, monolayer adsorption capacity, moisture absorption rate constant, Carr index and specific surface area were the key physical properties of hawthorn leaf granule to affect its dissolution behavior.
Résumé
OBJECTIVE: To establish the relationship between the physical parameters of granules and their dissolution behavior. METHODS: Andrographis paniculata (Burm. 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).