Characterization, stability and solubility of co-amorphous systems of glibenclamide and L-arginine at different pH

Abstract

Purpose: To investigate the stability and solubility of co-amorphous systems of glibenclamide (GBC) with L-arginine (L-Arg) at different pH values. Methods: Three co-amorphous solids of GBC and L-Arg were obtained by fast solvent evaporation using 2:1, 1:1 and 1:2 stoichiometries. All co-amorphous systems were characterized by XRPD, FTIR, RAMAN and NMR-solid state as well as thermal techniques such as DSC and TGA. The stability of coamorphous systems was evaluated by indicative stability and stability in relevant physiological media was measured at different pH values. Results: The chemical characterization suggest that there was no proton transference between L-Arg and GBC indicative of co-amorphous solids. Stability studies showed that all the co-amorphous solids are unstable under humid conditions and only the co-amorphous system of GBC: L-Arg 1:2 was stable in all the pH values tested. Solubility studies at different pH values showed that the co-amorphous GBC: L-Arg 1:1 and 1:2, showed increasing solubility values even at pH < 7 (0.6468 mg/mL at pH 1.2 for coamorphous GBC: L-Arg 1:2 at the first hour) where free GBC was not soluble. Conclusion: Co-amorphous systems of GBC and L-Arg, is an interesting strategy to increase the solubility of poorly-soluble drugs at acidic pH values Keywords: Co-amorphous; Glibenclamide; L-Arginine; Solubility; Stability