Study on sustained-release morphine sulfate suppository made of different bases in vitro release and its pharmacokinetics / 中国药学杂志

ABSTRACT

A series of sustained-release morphine sulfate suppositories were prepared with two kinds of different bases according the qualified formulations (r2 > 0.9). The best formulation was determined by melting point, drug release in vitro and rectal administration in rabbits. A self-made device was used to evaluate drug release in vitro. The 3p97 program was used to calculate the pharmacokinetic parameters of morphine sulfate suppositories. Comparative studies on characteristics in vitro release and in vivo pharmacokinetics of sustained-release morphine sulfate suppositories were carried out. Drug release pattern in vitro was best described by zero-order kinetics and in vivo profile was demonstrated to fit single compartment model. When r2 > 0.95, the plasma concentration in vivo shown a platform. The MRTs of F4 and P4 were 16.72 and 9.19 h, which shown that the poloxamer-based morphine sulfate suppository F4 had better sustained-release performance. The pharmacokinetics pharmerers were t1/2(ke) =7.225 h, tpeak =5.107 h, ρmax = 1141 ng · mL-1, AUC =22817 ng · h · mL-1. The prepared poloxamer-based suppository of morphine sulfate F4 exhibits sustained-release profile in vivo, which has the value of industrialization. Copyright 2012 by the Chinese Pharmaceutical Association.