Title
Formulation, optimization and in vitro evaluation of a cellulose derivative-based matrix system for extended-release metformin using response surface methodology
Authors
ANIS AMTSIF, FAIZA ZERMANE, BENAMAR CHEKNANE, SALIM DJELLOULI and HOUDA DOUBA

Received November 22, 2025
Published Volume 60 Issue 5-6 May-June
Keywords metformin, extended-release, hypromellose, formulation, experimental design

Abstract
This study aimed to develop and optimize an extended-release (ER) metformin hydrochloride matrix tablet using hypromellose as the matrix-forming polymer. ER formulations of metformin are crucial as they provide stable plasma concentrations, reduce dosing frequency and gastrointestinal side effects, enhancing patient adherence and glycemic control. A D-optimal experimental design combined with response surface methodology (RSM) was used to evaluate the impact of formulation variables (povidone K30, hypromellose, and lactose monohydrate) on tablet properties, such as friability, hardness, flowability, and moisture content. The optimal formulation containing povidone K30 (3.38%), hypromellose (19.6%) and lactose monohydrate (35.01%) exhibited drug release following the Korsmeyer Peppas model, with 78% of the drug released over 8 hours, showing extendedrelease behavior. Fourier-transform infrared spectroscopy indicated no significant chemical interaction between metformin and the excipients, while X-ray diffraction showed that metformin retained its crystalline structure. DSC–TGA analysis further confirmed the stability of metformin and its compatibility with the excipients. This optimized extended-release formulation may represent a simple, cost-effective, and practical alternative for diabetes management in resource-limited settings, owing to its straightforward preparation process and the absence of requirements for specialized manufacturing technology.