In vitro Dissolution and in vivo Bioequivalence Evaluation of Two Brands of Cefuroxime Axetil Tablets

Abstract

The bioequivalence of two brands of 250 mg cefuroxime axetil (CAS 64544-07-6) tablets was evaluated by in vitro dissolution tests and in vivo bioequivalence tests. The in vitro dissolution test was performed by the paddle method following the guidance of the Korea Food and Drug Administration (KFDA). The in vivo bioequivalence study was designed to be a single dose, randomized, double-blind trial with a 1-week washout period between the doses in 26 healthy volunteers. The results of the dissolution test showed comparable and rapidly dissolving profiles of the two cefuroxime axetil tablets, which were pharmaceutically equivalent. The in vivo study was conducted to evaluate the bioequivalence of the two drug products in humans. In the in vivo bioequivalence study, the plasma samples drawn from the volunteers were analyzed utilizing a sensitive HPLC analysis method with ultraviolet detection. The evaluation of bioequivalence between test and reference products was accomplished by statistical analysis of the log transformed mean ratios of Cmax, AUC0–t and AUC0–8. The mean maximum concentration (Cmax) of the test and the reference were found to be 8.5 ± 2.0 µg/mL and 8.6 ± 2.1 µg/mL, respectively. The 90% C. I. of Cmax was 0.95 to 1.03. As for the AUC0–t and the AUC0–8, test values were 22.6 ± 5.7 µg mL−1 h, 23.5 ± 6.3 µg mL−1 h and the reference values were 25.6 ± 6.6 µg mL−1 h, 26.7 ± 6.8 µg mL−1 h, respectively. The 90% C. I. of AUC0–t was 0.83 to 0.94 and AUC0–8, 0.82 to 0.94. Consequently, all the results fulfilled the standard criteria of bioequivalence, being within the 0.80 to 1.25% range. In addition to the 90% C. I. of the parameters, a two-way ANOVA showed that there was no significant difference between the two products. Based on these statistical analyses, it is concluded that the test product is bioequivalent to the reference product.