Correlation of Solubility Thermodynamics of Glibenclamide with Recrystallization and In Vitro Release Profile

Abstract

The solubility of glibenclamide was evaluated in DMSO, NMP, 1,4-dioxane, PEG 400, Transcutol® HP, water, and aqueous mixtures (T = 293.15~323.15 K). It was then recrystallized to solvate and compressed into tablets, of which 30-day stability and dissolution was studied. It had a higher solubility in 1,4-dioxane, DMSO, NMP (Xexp = 2.30 × 103, 3.08 × 104, 2.90 × 104) at 323.15 K, its mixture (Xexp = 1.93 × 103, 1.89 × 104, 1.58 × 104) at 298.15 K, and 1,4-dioxane (w) + water (1−w) mixture ratio of w = 0.8 (Xexp = 3.74 × 103) at 323.15 K. Modified Apelblat (RMSD ≤ 0.519) and CNIBS/R-K model (RMSD £ 0.358) suggested good comparability with the experimental solubility. The minimum value of ΔG˚ vs ΔH˚ at 0.70 < < 0.80 suggested higher solubility at that molar concentration. Based on the solubility, it was recrystallized into the solvate, which was granulated and compressed into tablets. Among the studied solvates, the tablets of glibenclamide dioxane solvate had a higher initial (95.51%) and 30-day (93.74%) dissolution compared to glibenclamide reference (28.93%). There was no stability issue even after granulation, drying, or at pH 7.4. Thus, glibenclamide dioxane solvate could be an alternative form to improve the molecule’s properties.

Bioavailability and Antihyperglycemic Effect of Four Glibenclamide Tablets: A Comparative Study

“…However, at these pH levels, the solubility of glibenclamide is minimal. Consequently, the presence of the drug in a rapidly dissolving formula is essential to ensure complete absorption from the acidic media of the upper gastrointestinal tract [24][25][26] . In this study, Euglucon ® tablets (in micronized form) and X-brand tablets (not micronized form) were used for further studies.…”