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

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 co-amorphous 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 co-amorphous 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