Pharmacokinetics of drug resin complexes osmotic pump tablet loaded propranolol in Beagle dogs

AIM To determine the pharmacokinetics of drug resin complexes osmotic pump tablet (DRCOPT) loaded propranolol in Beagle dogs and study the correlation between absorption in vivo and release in vitro for DRCOPT loaded propranolol.METHODS According to a two-way crossover design,six Beagle dogs were administrated with propranolol in conventional tablets and DRCOPT orally.Plasma concentration of two preparations was determined by HPLC method and pharmacokinetic parameters were calculated by DAS 2.0 software.In vitro drug release was determined by UV spectrophotometer and the correlation was studied by the test of in vitro dissolution and in vivo pharmacokinetics through Wanger-Nelson method.RESULTS The lag time of release in vitro was 2 h and accumulative release was over 90 % in 24 h.The minimal effective concentration was detected after 5 h in in vivo test.Main pharmacokinetic parameters of conventional tablet and DROPTwere as follow:t_(max) (11.0±s 1.1) and (3.0±0.6) h,t_(1/2) (6±4) and (3.2±0.6) h,c_(max)(128±11) and (750±55)μg·L~(-1),AUC_(0-∞)(2583±508) and (2708±386)μg·h·L~(-1).A good correlation in vivo and in vitro was observed.CONCLUSION The lag time of DRCOPT loaded propranolol provides possibility for time-controlled administration.Compared with conventional tablet,propranolol concentration of DRCOPT in plasma is steady and can maintain effective plasma drug concentration levels for a longer duration.