Rheological and Thermal Behavior of Choline-based Deep Eutectic Ionic Liquid and its Impact on a Poorly Soluble Drug Model

Abstract

Objective: This study was conducted to prepare a deep eutectic ionic liquid based on choline chloride and malonic acid (Maline) in diff erent molar ratios and evaluate the maline properties to designate the best ratio for solubilizing risperidone, a poorly soluble drug model. Method: Malines were prepared using choline chloride and malonic acid in 1:0.8, 1:0.9 and 1:1 molar ratios. The characterization of malines involved pH rating, rheological test and thermal behavior using DSC. In addition to estimating the interactions that occur between the choline chloride and malonic acid to form the malines theoretically using the computational prediction program Mercury and experimentally by 1H-NMR and FTIR. Results: This study shows that all malines (M1-M3) represents an acidic pH and high viscosity with a non-newtonian behavior (shear thinning property ) at low temperature while a Newtonian behavior (shear rate-independent) at high temperatures. In malines (M1-M3) thermograms, the absence of pure compounds melting point peaks with a glass transition temperature at -14○C that confi rms the DES property. FTIR and 1H-NMR results represent a hydrogen bond formation between choline chloride and malonic acid and further between maline and risperidone which is similar to the computational prediction. Maline (M1) with molar ratio of 1:1 had a preferable solubilizing eff ect on risperidone reaching 20.5 mg/mL, while in (M2) (1:0.9) reaches 13.6 mg/mL, and in (M3) reaches 11.9 mg/mL. Conclusion: Maline (M1) was chosen as the optimum molar ratio to form a deep eutectic ionic liquid that successfully enhances risperidone solubility and boosts its bioavailability.