In vitro and in vivo studies on slow release propranolol hydrochloride suppositories. Pharmacokinetic and pharmacodynamic evaluation.

Matrix-based slow release (SR) compressed propranolol HCl (25 mg) suppositories were formulated using PEG 4000 and either stearic acid or bees wax at different concentrations (5, 7.5 and 10%). In vitro studies revealed good slow release characteristics from the suppositories. Their in vivo performances--pharmacokinetics and pharmacodynamics--were evaluated in rabbits. Different pharmacokinetic parameters were determined from the plasma concentration-time profiles using a model-independent computer programme, RAMKIN. The relative bioavailability of propranolol (CAS 525-66-6) from three SR suppositories containing stearic acid, 7.5 and 10% and bees wax, 5%, was 86.4, 87.8, and 83.6% respectively. Pharmacodynamic response (beta-blockade) was assessed by determining the degree of reduction of isoprenaline-induced tachycardia at different time intervals. A minimum concentration of 40-60 ng/ml drug in plasma was maintained during 1-10 h, and there has been a minimum of about 40-50% of beta-blockade during 1-9 h post administration. A good correlation between pharmacokinetic and pharmacodynamic profiles was observed.