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.
Sastri
M S
MS
Pharmacology Section, Indian Institute of Chemical Technology, Hyderabad.
Satyanarayana
N V
NV
Krishna
D R
DR
Diwan
P V
PV
D000818:Animals; D001682:Biological Availability; D003692:Delayed-Action Preparations; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D011433:Propranolol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D013229:Stearic Acids; D013488:Suppositories; D014885:Waxes
D003692:Delayed-Action Preparations; D013229:Stearic Acids; D013488:Suppositories; D014885:Waxes; C038228:beeswax; C031183:stearic acid; D011433:Propranolol