Strategic Formulation and Optimization of A Hydrodynamically Balanced Oral Delivery System for Sustained Antidiabetic Therapy

Abstract

The present study aimed to develop and evaluate a hydrodynamically balanced gastroretentive drug delivery system of Buformin to improve therapeutic efficacy in the management of Type 2 Diabetes. A 2⁴ factorial design was employed to optimize the formulation variables, including Hydroxypropyl Methylcellulose (HPMC K4M), Hydroxyethyl Cellulose (HEC), hydrophobic fatty base (Cetyl Alcohol), and effervescent agent Sodium Bicarbonate (NaHCO₃).A total of sixteen formulations were prepared during the optimization phase and categorized into six groups (Group I–VI) for systematic analysis, with formulation variables varied at different levels. The independent variables (HPMC K4M, HEC, Cetyl Alcohol, and NaHCO₃) were evaluated for their effects on drug release and floating behavior.Pre-compression parameters such as angle of repose, bulk density, compressibility index, and Hausner’s ratio were assessed to determine flow properties. Post-compression evaluation included thickness, hardness, friability, swelling index, floating lag time, total floating duration, and in vitro drug release.Among the formulations, the angle of repose ranged from 15.23° (F15) to 30.15° (F12). Bulk density was highest in F8 and lowest in F4. Carr’s index was highest in F2 and lowest in F6, indicating superior compressibility characteristics in formulations with lower values. Friability was highest in F9, whereas hardness was highest in F8 and lowest in F15. Swelling behavior varied significantly among formulations, with F10 exhibiting the highest swelling index (42.16), indicating superior matrix hydration and retardation capability.Floating characteristics were evaluated using 400 mL of 0.1N HCl. In vitro dissolution studies were performed in 0.1N HCl buffer (pH 1.2), and drug release was analyzed at 235 nm using UV spectrophotometry. The results demonstrated that formulation variables significantly influenced tablet buoyancy, swelling behavior, and drug release profile.The main effects of variables A, B, C, and D were determined by evaluating the average response resulting from variation of one independent variable from low to high level while keeping others constant. Interaction effects including AB, AC, AD, BC, BD, CD, ABC, ABD, ACD, BCD, and ABCD were also analyzed to understand the combined influence of multiple variables on dependent responses. Factorial analysis confirmed that polymer concentration, hydrophobic matrix content, and effervescent agent levels played crucial roles in optimizing gastroretentive performance and sustained drug release. The optimized formulation demonstrated desirable floating behavior, prolonged gastric retention potential, and controlled drug release, suggesting that the developed hydrodynamically balanced gastroretentive system of Buformin may serve as a promising approach for improved management of Type II Diabetes Mellitus.