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

The bioequivalence of three chemically equivalent paracetamol generic Mexic an products (500 mg tablets) was evaluated in 12 healthy volunteers using t he American innovator product (Tylenol, McNeil, Fort Washington, PA), as th e 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 tak en as a measure of bioavailability. In addition, moment analysis was used t o estimate in vitro mean dissolution time (MDT) from dissolution profiles o btained following the USP 23 dissolution test specified for paracetamol tab lets and to estimate in vivo mean residence time (MRT) from urinary excreti on data. significant differences in the dissolution performance and in the cumulative amount of paracetamol excreted in urine up to 24 hr were observe d when the data were analyzed by analysis of variance (ANOVA) (p < .05). Cl assical and Westlake 90% confidence limits, as well as the two-sided t test proposed by Schuirmann, and the Anderson-Hauck power analysis supported th e final conclusion that only one of the three generic paracetamol products studied can be considered equivalent to the reference product Tylenol. A li near correlation between in vitro MDT and in vivo MRT was found.