Bioequivalence study of paracetamol tablets: in vitro-in vivo correlation.

The bioequivalence of three chemically equivalent paracetamol generic Mexican products (500 mg tablets) was evaluated in 12 healthy volunteers using the American innovator product (Tylenol, McNeil, Fort Washington, PA), as the reference. Single oral doses of each product were administered at 1-week intervals using a 4 x 4 Latin square design balanced for the first residual effect. The total amount of paracetamol excreted in urine in 24 hr was taken as a measure of bioavailability. In addition, moment analysis was used to estimate in vitro mean dissolution time (MDT) from dissolution profiles obtained following the USP 23 dissolution test specified for paracetamol tablets and to estimate in vivo mean residence time (MRT) from urinary excretion data. Significant differences in the dissolution performance and in the cumulative amount of paracetamol excreted in urine up to 24 hr were observed when the data were analyzed by analysis of variance (ANOVA) (p < .05). Classical and Westlake 90% confidence limits, as well as the two-sided t test proposed by Schuirmann, and the Anderson-Hauck power analysis supported the final conclusion that only one of the three generic paracetamol products studied can be considered equivalent to the reference product Tylenol. A linear correlation between in vitro MDT and in vivo MRT was found.