Bioequivalence Studies of Itraconazole Capsules

Abstract

Objectives: To compare pharmaceutical properties and perform bioequivalence studies of two generic products with the innovative product, Sporal®.

Methods: The pharmaceutical  properties ; weight variation, content uniformity,  percent  labeled amount, and dissolution profile, of two itraconazole  generic products  (Product A and Product B) were

investigated and compared with those of the innovative itraconazole capsule, Sporal®. Two  bioequivalence

studies between product A or B with Sporal® were performed using 12 healthy Thai male volunteers for each study. A  200-mg single oral dose of itraconazole was administered immediately after breakfast. The study followed a double blind , two treatment, two period, two sequence randomized crossover design with at least a one-week wash out period between each formulation . Plasma concentrations of itraconazole were determined up to 36 hours after each dose using a validated high-performance liquid chromatography method.

Results: The itraconazole content of Product A was not uniform but no difference in  dissolution profiles between Product A and Sporal® were shown. The dissolution profile of Product B was not similar to that of Sporal®. Statistical tests were carried out as stated in the USP 25 guidelines for bioequivalence studies

and 90% confidence intervals of the log of the ratios of either Cmax or AUC<f->last between product A and Sporal ®, and product B and Sporal®were outside the standard range 0.80 - 1.25.

Conclusion: In term of unchanged itraconazole , product A and B used in the studies was not bioequivalent to Sporal ®. Bioequivalence studies with hydroxy-itraconazole, an active metabolite of itraconazole, should be performed to determine the overall therapeutic effects. Long term use in patients should also be determined to evaluate the therapeutic effects.