Bioavailability and in vitro dissolution of tiopinac from solution and capsule formulations

Abstract The absorption of a 75 mg dose of tiopinac, a non-steroidal anti-inflammatory agent, given orally as: (a) a solution; (b) capsules containing milled tiopinac; (c) capsules containing coarse topinac; and (d) capsules containing the sodium salt was evaluated in human volunteers. Also, in vitro dissolution studies were performed under different conditions on the dosage forms under study. The total absorption of tiopinac was complete from all dosage forms tested; however, the absorption rate was substantially and significantly affected by the dosage form. The order of the dosage forms according to decreasing absorption rate was: (1) solution; (2) sodium tiopinac capsules; (3) milled tiopinac capsules; (4) coarse tiopinac capsules. Using maximum plasma levels to reflect absorption rate these differences were statistically significant except for the milled vs coarse capsule comparison. Time to maximum plasma levels for each formulation were also compared. Some of the plasma profiles following the capsule doses exhibited ‘double peaks’, which was especially true in the case of the milled tiopinac formulation. This phenomenon was believed to be due to several factors: (a) the fact that 3 capsules (25 mg each) were administered; (b) ‘gastric-emptying-rate’ controlled absorption; and (c) the rapid distribution and elimination kinetics of tiopinac. In vitro dissolution conditions were established that correlated in vitro dissolution rate, tiopinac particle size (specific surface area) and in vivo absorption rate for the tiopinac acid capsule formulations. The in vitro dissolution conditions required modification to correlate the dissolution rate of the acid tiopinac capsules and the sodium salt tiopinac to correspond to their in vivo absorption rates. The effects of the dissolution medium and the dissolution apparatus on in vitro dissolution were also presented and discussed.