Relative Bioavailability Study of Succinic Acid Cocrystal Tablet and Marketed Conventional Immediate Release Tablet Formulation of Carbamazepine 200 Mg in Rabbits

A single-dose study was performed to observe the bioequivalence of the newly formulated carbamazepine-succinic cocrystal (CBZ-SUC) immediate release tablet (F1) with marketed immediate release formulation Epitol 200 mg tablet (F0). In this study on albino rabbits, the plasma levels resulting from 250 mg cocrystal equivalent to 200 mg of carbamazepine and conventional tablets 200 mg immediate release tablets were compared. An open-label, randomized 2 ◊ 2 crossover study design, with a 1-week washout period, was used. Carbamazapine (CBZ) plasma concentrations were determined by a high-performance liquid chromatography validated method using ultraviolet detection. CBZ plasma levels were measured at predose and various postdose time points up to 72 h and the following pharmacokinetic parameters were used for evaluation: area under the curve (AUC), maximum plasma drug concentration (Cmax), time to achieve Cmax (tmax), and elimination rate constant (Ke). By applying paired t-test to AUC0-72 (calculated by linear trapezoidal rule), the experimental formulation F1 was found to have statistically significant (***p < 0.05) improvement in bioavailability of CBZ. However, these statistical differences do not have practical implications and the two formulations (F0 and F1) were found to be bioequivalent as the relative bioavailability of both formulations (106.9%) falls within the acceptable FDA set range of two bioequivalent products 80-125%.