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Arzneimittelforschung 2012; 62(07): 335-339
DOI: 10.1055/s-0032-1312600
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

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

P. Zakeri-Milani
1   Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
2   Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
,
S. Ghanbarzadeh
3   Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4   Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
,
H. Valizadeh
1   Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
5   Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
› Author Affiliations
Further Information

Publication History

received 07 January 2012

accepted 20 April 2012

Publication Date:
30 May 2012 (online)

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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 (Cmax) and total exposure to 24 h (AUC24) 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 Cmax and 986.4±350.7and 1 035.8±350.3 ng.h/ml for AUC0–24 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 Cmax and 0.8886–1.0535% for AUC0–24. Therefore it can be concluded that both products are bioequivalent in terms of peak and total exposure and therefore interchangeable.

Key words

pentoxifylline - dissolution - bioavailability - bioequivalence
 

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