Development, characterization and pharmacodynamic evaluation of refined liquisolid system of glimepiride for bioequivalent tablet

Objective: This study explores the potential of a refined liquisolid system (RLS) for formulating glimepiride tablets, evaluating its drug release profile and pharmacodynamic effects in mice compared to the reference brand, Amaryl®.Background: Glimepiride, a third-generation sulfonylurea, is a weakly acidic hypoglycemic drug that falls under Class II in the Biopharmaceutical Classification System (BCS). Despite its effectiveness, glimepiride exhibits low solubility and high permeability, leading to inconsistent therapeutic outcomes. Materials and methods: The RLS formulations of glimepiride tablets were developed using 12 different combinations, incorporating Avicel PH 102 or Neusilin as adsorbents, propylene glycol or dimethyl sulfoxide as solvents, and croscarmellose sodium as a disintegrant. Various ratios of excipients to the active ingredient were evaluated, and the tablets were produced through direct compression. The formulations underwent dissolution testing in three simulated gastrointestinal fluids (pH 1.2, 4.5, and 6.8), two biorelevant media, and pharmacodynamic evaluation in normoglycemic mice. The similarity factor (f2) was employed to compare the dissolution profiles of the formulations with the innovator brand. Additionally, the area under the curve (AUC₀–₁₁ hours) and the mean maximum percentage reduction in blood glucose levels (%RBGL) of the RLS formulations were statistically compared to those of the reference. Results: The optimal glimepiride tablets were formulated using dimethyl sulfoxide as the solvent and either Avicel PH 102 or Neusilin as adsorbents. These RLS tablets demonstrated dissolution profiles closely matching those of the reference product, with similarity factor (f2) values exceeding 50. Furthermore, there was no statistically significant variation in %RBGL between the RLS tablets and the reference product (p > 0.05). Importantly, the glimepiride in the RLS formulation transitioned into an amorphous state. Conclusions: The RLS formulations offer a viable alternative for the industrial production of glimepiride tablets, providing a comparable therapeutic performance to the reference brand while potentially addressing solubility challenges.