Optimization of Preparation Process and Pharmacokinetics of APAP Double-Release Pellet Capsules

Abstract

In order to develop a kind of APAP double-release pellet capsules, which was prepared with the manual filling method, the immediate and sustained release pellets of a certain proportion were prepared by the fluidized bed coating and the extrusion spheroidization process, respectively. It was founded that both the prepared immediate-release pellets and sustained-release pellets had smooth and round surfaces. The particle size distribution ranged evenly from 16 to 35 mesh. Response surface plots showed that the optimal preparation prescription for immediate-release pellets were that ethanol concentration (X1) 70%, APAP 20%, MCC (X2) 40%, PVP K30 (X3) 20%, and sucrose pellet core 20%; and the optimal preparation prescription for sustained-release pellets were that HPMC concentration (X*3) 6.5%, APAP 30%, EC (X*1) 20%, MCC (X*2) 40%, PVP K30 4%, and lactose 6%. The results of pharmacokinetic analysis revealed that, after the APAP double-release pellet was orally administered, compared with that of conventional tablets, the plasma APAP levels in the blood circulation dramatically rose to significant peaks as a result of the quick and slow release of APAP from the capsules, which significantly prolonged the effective time of drugs in blood. Finally, immediate and sustained antipyretic-analgesic effects were obtained.