Highly Soluble Ternary Amorphous Glibenclamide-Arginine-Folic Acid Formulation Using Arginine as a Coformer, and...

Area of Science:

• Pharmaceutical Science
• Drug Delivery
• Materials Science

Background:

• Pregnant women often require medications like glibenclamide (GBC) for gestational diabetes and folic acid (FA) for preventing newborn malformations.
• GBC and FA exhibit low solubility and bioavailability, necessitating improved formulation strategies.
• Amino acids (AA) are known to enhance drug solubility as co-formers in amorphous systems.

Purpose of the Study:

• To prepare and characterize highly soluble pharmaceutical ternary formulations of glibenclamide (GBC) with folic acid (FA) and arginine (ARG).
• To investigate the role of arginine (ARG) as a co-former and wettability agent in GBC-FA ternary systems at various molar ratios.
• To assess the impact of these ternary formulations on the solubility and potential for combination therapy.

Main Methods:

• Ternary amorphous systems of GBC, FA, and ARG were prepared using ball milling at different molar ratios (1:1:0.4, 1:2:0.4, 1:10:0.4).
• Amorphization was confirmed using techniques such as differential scanning calorimetry (DSC) for glass transition, Fourier-transform infrared spectroscopy (FT-IR) for functional groups, and X-ray diffraction (XRD) for crystallinity.
• Solubility studies were conducted to quantify the enhancement achieved in the prepared formulations.

Main Results:

• Ball milling successfully produced amorphous GBC-ARG-FA systems, confirmed by the absence of XRD peaks and presence of glass transition.
• Arginine (ARG) demonstrated a dual role as a co-former and wettability agent, dependent on its concentration.
• The GBC:ARG:FA ternary formulation at a 1:10:0.4 molar ratio achieved a remarkable 897-fold solubility enhancement in the physical mixture and a 1287-fold increase in the amorphous formulation.

Conclusions:

• Ternary formulations of glibenclamide (GBC), folic acid (FA), and arginine (ARG) significantly enhance GBC solubility.
• Arginine's concentration-dependent role as a wettability agent and co-former is crucial for improving GBC bioavailability.
• These highly soluble ternary systems present a promising avenue for combination therapy in managing gestational health conditions.