Pharmacokinetic and Bioequivalence of Mirtazapine Orally Disintegrating Tablets: A Randomized, Crossover Study.

The study aimed to assess the bioequivalence of a new generic orally disintegrating tablet (ODT) formulation containing mirtazapine 30 mg with the reference formulation, and to support biowaiver for an additional 15 mg strength. Fifty-five healthy Malaysian males completed an open-label, balanced, randomized, 2-treatment, 2-period, single oral dose study with a 14-day washout period under fasting conditions. Each participant received a single 30 mg dose of mirtazapine test or reference ODT. Plasma concentrations of mirtazapine up to 72 h post-dose were quantified using a validated high-performance liquid chromatography-tandem mass spectrometry detection method following a liquid-liquid extraction. Non-compartmental analysis was used to derive the pharmacokinetic parameters, which were then compared between the test and reference formulations using a multivariate analysis of variance. The pharmacokinetic parameters of the test formulation were not statistically different from the reference formulation. The 90% confidence intervals of mirtazapine for AUC0-72 and Cmax concentration were within 80%-125% based on the bioequivalence acceptance range criteria. The test and reference formulations of mirtazapine 30 mg ODT are bioequivalent and well tolerated under fasting conditions. These findings support the extrapolation of bioequivalence and the justification of a biowaiver for the additional mirtazapine ODT 15 mg strength.