Design and Evaluation of Controlled-Release Floating Metformin HCl Tablets: Influence of Binder and Granulation Process on Buoyancy

Abstract

Scope and objective: Objective of this study is to investigate how the combined effects of binder properties and granulation parameters shape the development and performance of controlled-release floating Metformin HCl tablets. It focuses on evaluating the suitability of various grades of Polyvinyl Alcohol (PVA) as granulating binders and assessing how alterations in top-spray granulation conditions influence tablet buoyancy and drug-release characteristics when Eudragit NE 30D is employed as the release-controlling coating polymer. Methodology: Granules were produced using a low-shear top-spray granulation process with PVA serving as the binder. An experimental study was designed to evaluate the influence of various PVA grades on buoyancy performance and to assess process-related effects by comparing fast and slow spray rates at different inlet temperatures using optimized PVA 40 cP. Compressed tablets were coated with Eudragit NE 30D, followed by comprehensive evaluation involving physicochemical testing, in vitro swelling and erosion studies, dissolution profiling, and in vivo buoyancy assessment. Drug-release kinetics were modeled to characterize the underlying release mechanisms. Results: Of the formulations tested, MTH3, prepared with PVA 40 cP, exhibited rapid flotation (within 30 seconds) and maintained buoyancy for more than 16 hours. Lower-viscosity PVA grades did not yield floating systems. In the process-optimization phase, MTH3 manufactured using a faster spray rate outperformed MTH4, which was produced using a slower spray rate and required approximately 90 minutes to float. MTH3 also demonstrated nearly complete drug release (~98.7%) over more than 16 hours, whereas MTH4 released only 83.3% within the same period. Release-kinetic analysis indicated that MTH3 followed Higuchi behavior, suggesting a diffusion- and erosion-driven release pattern. Dissolution similarity (F2) remained unchanged under accelerated stability conditions. Conclusions: The combination of PVA 40cP and a fast top-spray granulation rate was identified as the optimal approach for producing floating controlled-release Metformin HCl tablets. This formulation strategy resulted in tablets with rapid and prolonged buoyancy, robust sustained-release characteristics, and strong stability performance, establishing it as a promising platform for enhanced gastro-retentive drug delivery of Metformin HCl.