Promising Swellable Floating Bupropion Tablets: Formulation, in vitro/in vivo Evaluation and Comparative Pharmacokinetic Study in Human Volunteers

摘要

Purpose: Bupropion is an antidepressant drug that facilitates weight loss. It is a highly water-soluble drug that needs multiple dosing, so it is considered a potential candidate for oral controlled-release dosage form. The aim of this research was to formulate and evaluate satiety-inducing swellable floating bupropion tablets by direct compression targeting depression associated with eating disorders. Various combinations of natural and semi-synthetic hydrogels were selected to achieve maximum swelling and remaining buoyant in the stomach. This synergistically enhances weight loss by increasing satiety. Methods: An I-optimal mixture design was conducted to establish the optimal quantitative composition of tablets. Friability, floating lag time, swelling index after 4 and 8 hours, along with the percent of bupropion released at 1 and 8 hours were selected as dependent variables. The optimized formulation was characterized by physicochemical properties, thermal stability, and chemical interaction. In vivo radiographic evaluation of gastric residence besides, the oral bioavailability relative to marketed Wellbutrinsup?/sup sustained-release tablets were investigated using human volunteers. Results: The optimized formulation (73.3 mg xanthan, 120 mg glucomannan, 8.4 mg tamarind kernel powder, 78.3 mg HPMC K15M) was achieved with the overall desirability equals 0.782. In vivo radiographic study showed that formulation was retained for 8 hours in the stomach. Compared with the marketed BUP tablets, the Csubmax/sub was almost the same with a significant increase (p =0.004) for Tsubmax/sub. Conclusion: Using combinations of these hydrogels would be promising gastroretentive delivery systems in the control of bupropion rate release with enhanced floating and swelling features.