Comparative in vitro Dissolution and in vivo Bioequivalence of 2 Pentoxifylline Sustained Release Formulations

Abstract

Pentoxifylline is a xanthine derivative that is indicated for the treatment of patients with intermittent claudication on the basis of chronic occlusive arterial disease of the limbs. In the present study, prior to the in vivo study, an in vitro comparative dissolution test was performed by the paddle method for 2 oral sustained release pentoxifylline tablets (400 mg) following the bioequivalence guidance of FDA. Metrics of peak exposure (C-max) and total exposure to 24h (AUC(24)) were compared using a randomized, single oral, open-label, 2-period, 2-sequence, 2 treatments crossover study in 24 healthy male volunteers under fasted conditions. After an overnight fast, the volunteers received 400 mg pentoxifylline and the blood samples were collected over a 24-h period following drug administration. Plasma drug concentrations were measured by a reverse-phase HPLC method with ultraviolet detection. In vitro dissolution tests requirements were met by both formulations. Observed exposure metrics for test and reference products were 140.6 +/- 51.5 and 132.6 +/- 48.5 ng/ml for C-max and 986.4 +/- 350.7 and 1035.8 +/- 350.3 ng.h/ml for AUC(0-24) respectively. The confidence intervals (90%) around ratios (test/reference) of least squares means derived from logarithmic transformed exposure metrics were 0.9912-1.1564% for C-max and 0.8886-1.0535% for AUC(0-24). Therefore it can be concluded that both products are bioequivalent in terms of peak and total exposure and therefore interchangeable.