Impact of Process Parameters on the Quality Attributes of High-Dose Metformin Hydrochloride Film-Coated Tablets

Background/Objectives: Formulating high-dose metformin hydrochloride film-coated tablets is challenging due to the poor flowability and compressibility inherent to high drug loading. To ensure process robustness and consistent product quality, understanding the impact of manufacturing variables is crucial. This study evaluated the effects of key process parameters on the quality attributes of 1000 mg metformin hydrochloride tablets to establish optimal processing conditions for reliable production. Methods: The manufacturing process, comprising wet granulation, compression, and film coating, was investigated to evaluate the influence of key process parameters on tablet quality attributes. Granules were characterized for bulk density, tapped density, and compressibility index. Core tablets were evaluated for physical appearance, weight variation, hardness, and dissolution at a 45 min sampling point across various compression forces and tableting speeds. Film-coating efficiency was assessed based on coating quality, dissolution behavior, and stability. Favorable manufacturing conditions were empirically identified through single-variable optimization and statistical analysis. Results: Wet granulation conducted at a chopper speed of 1400 rpm for 7 min yielded granules with the lowest compressibility index (11.88%), demonstrating significantly improved flowability. Compression at a force of 10 kN and a speed of 40 rpm produced core tablets with acceptable appearance, robust hardness (7.06-7.37 kP), and complete drug release (100%). Tablet hardness was governed by a strong interaction between compression force and tableting speed (partial η² = 0.929, p < 0.001) rather than by either factor alone: at 20 kN, hardness collapsed sharply once tableting speed reached 30 rpm, coincident with mild capping, identifying this force-speed combination as a process-failure condition. For the coating process, maintaining a tablet bed surface temperature of 40 °C ensured optimal coating uniformity without compromising product quality. Dissolution profile comparison against a coated reference product in the primary dissolution medium (pH 6.8) yielded f2 similarity values above 50 for all eight core tablet conditions, and stability testing under accelerated/thermal-stress conditions (up to 65 °C) confirmed maintained dissolution, assay, and related-substance (1-cyanoguanidine) compliance for both the test and reference products. The optimized manufacturing conditions successfully produced film-coated tablets that conformed to all predetermined quality specifications. Conclusions: Manufacturing process parameters significantly influenced the quality attributes of high-dose metformin hydrochloride film-coated tablets. Proper selection and control of these processing conditions ensured consistent granule properties, optimal tablet quality, and enhanced manufacturing robustness.