Abstract
Purpose: To investigate the pharmacokinetics of of a developed metoprolol and a reference standard (Mepressor®).Methods: Metoprolol tartrate-loaded Eudragit® FS microparticles were formulated and compressed into tablets. The tablets were tested for their physicochemical properties according to United States Pharmacopoeia (USP) criteria. In vivo studies of the formulations were carried out in 28 young healthy fasting male volunteers based on a randomized open label 4×4 crossover study design with a washout period of 7 days.Results: In vitro tests showed that the developed and reference standard of metoprolol tablets met compendia (USP) requirements. Zero order release of drug was observed from all the tablets. In vivo data demonstrated that there were significant (p < 0.05) differences in tmax, Cmax, MRT, AUC0−t, and AUC0–∞ between the reference and test (developed) formulations. However, the 90 % class interval for the mean ratios of the ln-transformed Cmax, AUC0-t and AUC0-α for the reference, T1, T2, and T3 lied in the bioequivalence range (80 to 125 %) indicating bioequivalence between the compared formulations. Conclusion: It can be concluded from this single-dose study that the reference and test (developed) formulations met the predetermined criteria for bioequivalence in young healthy fasting male human subjects as the bioequivalence factor lie in the pre-determined limits for bioequivalence. Thus, the two formulations can be considered bioequivalent.Keywords: Metoprolol tartrate, Eudragit® FS, Microparticles, Bioavailability, Pharmacokinetics.
Highlights
Β-blockers, oxprenolol and metoprolol are well absorbed in the colon as well as in the small intestine
These values indicate that the method used has high repeatability and precision for metoprolol analysis
The weight variation, hardness, friability, disintegration, and dissolution for all formulations were within allowed limits of United States Pharmacopoeia (USP) [7]
Summary
Β-blockers, oxprenolol and metoprolol are well absorbed in the colon as well as in the small intestine. The mean time to reach maximum plasma concentration and mean elimination half life for metoprolol after oral dosing are 2 h and 4 h, respectively. Evaluation of the weight variation, tablet hardness, friability, disintegration and dissolution of the reference and test tablets were performed Based on these considerations, this study was designed to develop suitable metoprolol - Eudragit® FS extended and targeted release pH-dependent tablet formulations. Based on the non-compartment model approach, the values of Cmax (maximum drug concentration in plasma), tmax (time to reach peak concentration), AUC (area under the curve), Ke (elimination rate constant), t1/2 (biological half life) and MRT (mean residence time) were measured from plasma metoprolol concentration versus time profiles for each volunteer, using Microsoft Excel, 2007 [1]. Two compared formulations were considered bioequivalent if the 90% class intervals (CIs) for these ratios lie between 80 and 125 % [1]
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