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

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 Wellbutrin® 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 Cmax was almost the same with a significant increase (p =0.004) for Tmax. 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.

Formulation, Characterization and Comparative Pharmacokinetic Study of Bupropion Floating Raft System as a Promising Approach for Treating Depression.

The aim of this study was to formulate, evaluate, and compare satiety-enhancing floating raft system (FRS) of bupropion as gastroretentive drug delivery systems (GRDDS) using in-situ gelling pectin and alginate. Bupropion was considered as a good candidate for such systems due to high water solubility that requires frequent dosing. Pectin and alginate could prolong satiety sensation augmenting weight loss of bupropion. A 24 full factorial design was tailored to inspect the effect of the response variables (gel-forming polymer type, calcium carbonate percentage, glyceride lipid type and percentage). Gelation lag time, floating lag time, as well as drug released percent after 1 and 8 h were selected as dependent variables. The optimal system was investigated for compatibility and bioavailability study in healthy human volunteers relative to marketed Wellbutrin® sustained release tablets. The optimal FRS (3% alginate, 2% precirol®, and 2% CaCO3) was selected. This system had an optimum viscosity that will allow a rapid sol-gel transformation in the stomach, excellent floating behavior, and controlled release profile with a comparable bioavailability. The optimal FRS would be a novel liquid GRDDS in controlling bupropion rate release especially for depression associated with eating disorders or dysphagia improving patient compliance and drug efficacy.

Content uniformity testing: suitability of different approaches for marketed low dose tablets.

CONTEXT: Content uniformity (CU) testing was developed and improved to control the effectiveness and safety of dosage units. Many modifications of compendial CU test have been introduced and several alternatives have been suggested. OBJECTIVES: This study aims to evaluate the degree of suitability of current USP CU test for low dose tablets and to compare the performance of the current test with that of the former USP27-NF22 and other alternatives for different sample sizes. METHODS: All locally marketed risperidone (RSP) tablets were analyzed using newly developed and validated isocratic UPLC method. The CU results were statistically analyzed in groups with sample sizes comparable to the USP sampling plans. RESULTS: Seven out of eleven products failed the different requirements of the former and current USP <905>chapters as well as of several alternative CU tests with several substantial deviations. CONCLUSION: The current USP <905> chapter was found to have some deficiencies that allowed such failed products to exist in the market. The dependence of compendial CU test on two-staged sampling plan and the use of arithmetic mean to calculate the reference and acceptance values were obvious shortcomings.