In vivo performance of wax matrix granules prepared by a twin-screw compounding extruder

The in vivo performance of wax matrix granules (WMGs) prepared by a twin-sc rew compounding extruder was evaluated in fasted beagle dogs. in vitro diss olution behavior of the model drug, diclofenac sodium (DS), from WMGs was s trongly influenced by pH in a dissolution medium due to its solubility (DS is soluble in pH 6.8 and insoluble in pH 1.2 and 4.0) and was independent o f paddle rotation rate (50, 100, and 200 rpm) of the dissolution apparatus. Pharmacokinetics parameters such as mean residence time (MRT) showed a sus tained action of WMGs in beagle dogs; however the transit time of WMGs in t he small intestine is found to control total drug absorption. Furthermore, the values of the area under the curve (AUC) of the plasma concentration-ti me curve and the maximum concentration C-max significantly decreased with d ecreases in hydroxypropylcellulose (HPC) content in WMGs. Good correlation between one in vitro dissolution parameter (mean dissolution time, MDT) and two in vivo parameters (AUC(12) and MRT) suggested that it would be possib le to design WMGs with a desired in vivo performance by controlling HPC con tent.