Biopharmaceutical evaluation of 'Osmosin'.

'Osmosin' is an osmotically-controlled oral drug delivery system which presents a saturated solution of sodium indomethacin trihydrate (105.4 mg), equivalent to 85 mg indomethacin, to the gastro-intestinal tract at a constant rate of 7 mg per hour, with a release time of 10 to 12 hours. Drug delivery is not influenced by pH or gastro-intestinal motility. The bioavailability and functionality of 'Osmosin' have been studied after single-dose and after repeated administrations in man. Its performance was compared to that after intravenous administration and various capsule regimens of indomethacin. In both studies, comparable urinary excretion and renal clearance for all oral regimens indicated that like amounts of drug were available for absorption from 'Osmosin' and 'Indocid' capsules. This comparability was verified by the fact that indomethacin is 85% bioavailable from 'Osmosin' compared to intravenous or oral regimens (75 mg given as one dose of 3 X 25 mg capsules or 25 mg 3-times). Drug is absorbed at a constant rate for about 4 hours after 'Osmosin' administration. Indomethacin plasma profiles on an 'Osmosin' 12-hourly regimen were different from typical indomethacin capsule regimens (25 mg at 0, 4, 8 hours; 75 mg at 12 hours or 50 mg at 0, 4 and 14 hours daily). Indomethacin plasma levels from 'Osmosin' were more uniform and sustained, demonstrating more even distribution of drug with time. The constant-rate delivery of sodium indomethacin trihydrate to the gastro-intestinal tract from 'Osmosin' controls the rate of drug absorption, prolongs the effective half-life of drug in plasma, does not inhibit the efficiency of absorption, but does significantly decrease the extremes in plasma level fluctuation noted with conventional dosage forms.