Highly Soluble Ternary Amorphous Glibenclamide-Arginine-Folic Acid Formulation Using Arginine as a Coformer, and Wettability Agent Academic Article in Scopus uri icon

abstract

  • Pregnant women must take medications to treat or prevent specific health conditions that arise during the gestational period. Glibenclamide (GBC), metformin (MET), or insulin (INS) can be prescribed to treat gestational diabetes; Folic acid (FA) is also prescribed during pregnancy to prevent newborn malformations. GBC and FA have low solubility and, therefore, low bioavailability. Amino acids (AA) have been previously proven to be efficient co-formers in binary systems, enhancing drug solubility in water. In this study, highly soluble pharmaceutical ternary formulations of GBC were prepared with FA and the amino acid arginine (ARG). Although ARG has been previously reported as a co-former in GBC binary co-amorphous formulations, it has not been studied in molar ratios higher than 1:2. The results show that ARG may play a role as a co-former and wettability agent depending on its concentration. Ball milling was chosen to prepare the amorphous systems, testing different molar ratios (GBC:ARG: FA at 1:1:0.4, 1:2:0.4, and 1:10:0.4). The presence of glass transition, broad FT-IR bands, and the absence of X-ray diffraction peaks confirmed amorphization of GBC in the milled samples. Solubility results show that ARG may act as a wettability agent when present in the ratio GBC:ARG:FA 1:10:0.4, since even in the physical mixture, an enhancement of GBC solubility of 897-fold was achieved, and as a co-former since the amorphous GBC-ARG-FA formulation showed an increment of 1287-fold. The enhanced solubility of GBC in these ternary systems makes them potential formulations for simultaneously addressing health conditions through combination therapy with FA. © The Author(s) 2025.

publication date

  • January 1, 2026