In Vitro and In Vivo Evaluation of Carbamazepine Sustained Release Tablets

Abstract

Background: The objective of this study was to design sustained release tablet of Carbamazepine, one of the drugs of choice for the treatment of epilepsy. Carbamazepine exhibit poor bioavailability and has a narrow therapeutic index. That means fluctuation in the drug concentration in blood pose serious risk of toxicity. This problem can be solved by a well-designed sustained release delivery systems that reduces the frequency and maintains a more uniform drug concentration in blood circulation and target tissue cells that avoid fluctuation in drug concentration in blood, exhibited after intermittent administrationMaterials and Methods: The tablets were prepared by well-established wet granulation method using natural gums, i.e., xanthan and guar gum as sustaining material. Before compression, the derived properties of granules were evaluated, for instance, angle of repose, bulk density, compressibility index and drug content. Subsequently, the granules were compressed into tablets using conventional rotary compression machine. The tablets were tested for friability, hardness, thickness, weight variation and content uniformity. The in vitro drug release from the tablet was studied using USP Apparatus II (Paddle Apparatus). Moreover, the pharmacokinetic studies were performed in rabbits.Results: Wet granulation method proved to be an effective method for preparation of sustained release Carbamazepine tablets. The granules exhibited good rheological properties. For instance, the angle of repose for all the formulations was found bellow 30º, which indicate good flow property of the granules. Moreover, the compressibility Index of the formulations ranges from 15.26 to 19.54 % for the formulations; which also confirm the optimum flow properties. The pharmaco-technical parameters of the tablets were in acceptable range. The dissolution studies revealed that drug to gum ratio, 1:2, for both the gums, i.e., Guar gum and Xanthan gum provided a distinctive sustain release of Carbamazepine up to 24 hours. The formulations. Moreover, all the formulations exhibited non-Fickian (Anomalous) release, i.e., combination of both diffusion and erosion controlled-drug release.Conclusions: The successful formulations G3 and X3 also qualified the accelerated stability testing and there were no significant changes in the physical appearance as well as in the amount of carbamazepine release even after adverse storage conditions.