Quality by design approach to the development of metformin hydrochloride granules with immediate and prolonged release
Influence of binder type on immediate and prolonged release behavior and granule characteristics
DOI:
https://doi.org/10.20450/mjcce.2026.3471Keywords:
metformin hydrochloride, Quality by Design, wet granulation, binder selection, prolonged-release granules, fluid-bed coatingAbstract
Metformin hydrochloride (MHCl) is administered at high doses and requires robust formulation strategies to balance rapid drug availability with controlled-release performance. This study applied a Quality by Design (QbD) framework to develop immediate-release (IR) and prolonged-release (PR) MHCl granules and to evaluate the impact of binder selection on product quality and release behavior. Formulations were produced via wet granulation using polyvinylpyrrolidone (PVP), gelatin, and pregelatinized starch 1500 as binders. PR granules were further coated with Eudragit® RS/RL using a fluid-bed process. Risk assessment tools (Ishikawa and FMECA) guided the identification of critical quality attributes (CQAs), critical material attributes (CMAs), and critical process parameters (CPPs). Compatibility studies confirmed the absence of drug–excipient interactions. All IR formulations demonstrated rapid dissolution (> 90% release within 5 min). Uncoated PR granules exhibited partial release control, while coated formulations showed binder-dependent differences in particle size distribution and dissolution performance. The gelatin-based PR formulation provided the most consistent release profile and the closest alignment with United States Pharmacopeia (USP) extended-release criteria, as it demonstrated low variability and minimal intermediate-point deviations. The study confirmed that binder selection was a high-impact critical material attribute for achieving robust prolonged-release MHCl granules within a QbD-driven development strategy.
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Copyright (c) 2026 Maja Todeska, Daniel Velickovski, Martina Gjorgjevska, Dragana Petrushevska , Teodora Tasevska, Lina Livrinska Trpeska, Nikola Geskovski, Katerina Goracinova, Emilija Atanasovska, Maja Simonoska Crcarevska
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