Modeling and Comparison of Dissolution.pdfVIP

Dissolution Technologies | MAY 2009 41 Modeling and Comparison of Dissolution Profiles of Diltiazem Modified-Release Formulations D. Samaha, R. Shehayeb, and S. Kyriacos1 Department of Pharmaceutical Sciences, School of Pharmacy, Lebanese American University, P.O. Box 36, Byblos, Lebanon e-mail: soula.boustani@.lb 1Corresponding author. ABSTRACT Generic drugs offer a cost-effective alternative to brand-name products. However, the main concern with modified-release formulations is the substitution of one product for another. Accordingly, the first objective of this study was to assess the interchangeability of the available diltiazem extended-release (ER) products on the basis of their in vitro dissolution characteristics using USP Apparatus 2 and 3. The second objective was to compare dissolution profiles in simulated fasted and fed states and determine whether there is a change in the mechanism of drug release. Dissolution profiles characterized using Apparatus 2 or 3 under fasted conditions were similar. However, Apparatus 3 testing provided a more discriminating and comprehensive evaluation of the drug release performance of ER products. Testing using Apparatus 3 in the fed state highlighted some difference in dissolution profiles, suggesting a food effect on drug release. This implies that, depending on the targeted concentration, a patient should be instructed whether to take the medication in fasted or fed state. The study therefore shows the necessity of testing the products in both fasted and fed states to determine their similarity and therapeutic interchangeability. Apparatus 3 testing was also more accurate in determining the release mechanism than the Apparatus 2 method. No change in the mechanism of drug release between fasted and fed state was observed. INTRODUCTION Diltiazem is an orally administered, nondihydropyri-dine calcium-channel blocker that is used for the treatment of hypertension and atrial fibrillation. According to the Bio