Solubility improvement of atorvastatin using deep eutectic solvents.

Abstract

Deep eutectic solvents (DESs) in pharmaceutical investigations are still largely unknown in terms of safety, environmental acceptability, and practical use. The investigation focus is primarily of attempts to improve solubility is examined using the co-crystallization approach, which follows similar principles to the production of eutectic mixtures. We will look into the eutectic mixture interaction between selected coformers (nicotinamide [NA], isonicotinamide, and citric acid as acceptors of hydrogen bond and atorvastatin calcium trihydrate [ATCH] as donors of hydrogen bond in the DES system, assisted by propylene glycol [PG]). The study found that the optimum interaction in the DES system for ATCH is using NA in PG as a carrier, with evaluation by polarization microscopy, Fourier transform infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC), verifying that the drug and the DES components have formed H-bonds. H-bond interactions had been recognized through FT-IR and DSC, revealing that the DESs with NA coformer can increase ATCH solubility, as shown in the phase diagram. The increase in solubility was fairly considerable, allowing ATCH to dissolve at high concentrations in DESs, with a solubility of 0.158 ± 0.098 mg/mL compared to 0.000597 ± 0.003 mg/mL in water. Thus, it is obtainable to conclude that among the selected coformers, the DES system with the potential for improving the solubility of ATCH is DESs with NA coformer assisted by PG.