Bioequivalence Study of Paracetamol Tablets: In Vitro-In Vivo Correlation

Abstract

The bioequivalence of three chemically equivalent paracetamolgeneric Mexican products (500 mg tablets) was evaluated in 12 healthy volunteersusing the American innovator product (Tylenol, McNeil, Fort Washington, PA),as the reference. Single oral doses of each product were administered at 1-weekintervals using a 4 × 4 Latin square design balanced for the first residualeffect. The total amount of paracetamol excreted in urine in 24 hr was takenas a measure of bioavailability. In addition, moment analysis was used toestimate in vitro mean dissolution time (MDT) from dissolution profiles obtainedfollowing the USP 23 dissolution test specified for paracetamol tablets andto estimate in vivo mean residence time (MRT) from urinary excretion data.Significant differences in the dissolution performance and in the cumulativeamount of paracetamol excreted in urine up to 24 hr were observed when thedata 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-Hauckpower analysis supported the final conclusion that only one of the three genericparacetamol products studied can be considered equivalent to the referenceproduct Tylenol. A linear correlation between in vitro MDT and in vivo MRTwas found.