Design of captopril sustained-release preparation with oily semisolid matrix intended for use in human subjects

Abstract A captopril sustained-release dosage form using oily semisolid matrix (OSSM) has been studied to develop a formulation useful in human treatment. Four OSSMs which had different in vitro dissolution rates were administered to human subjects. The resulting bioavailabilities revealed that the best OSSM suitable for humans had a faster in vitro dissolution rate than that for dogs. Another series of administrations of OSSM also showed that formulated ascorbic acid improved the bioavailability of OSSM, and that the bioavailability was sufficient for a sustained-release dosage form so long as the amount of ascorbic acid in the OSSM was more than 5 times that of the captopril by weight. Pharmacokinetic analysis was performed based on plasma concentrations of captopril in humans ( n = 8) after a single oral administration of conventional tablets or OSSM reformulated for humans. Calculated areas under the curve ( AUC s, 0-∞ h) of plasma captopril concentration were 250.5 for conventional tablets and 283.5 (ng·h/ml) for OSSM. The mean residence times (MRTs) obtained by both formulations were 1.75 h and 3.59 h, respectively. The duration time in which plasma captopril concentration stayed above 50% inhibitory concentration of angiotensin converting enzyme activity was calculated. Total duration time (TDT) per day of conventional tablets (12.5 mg) taken 3 times daily was calculated to be 10.95 h. The TDT of OSSM was 17.00 h when the OSSM (18.75 mg of captopril) was administered twice a day at 12-h intervals. Consequently, OSSM dosed twice a day is expected to show a greater efficiency than conventional tablets taken 3 times daily.