Solubility of cinnarizine in natural deep eutectic solvent (camphor + menthol) and correlation with different solubility models

Abstract

The objectives of the current investigation are (1) to determine the cinnarizine's equilibrium solubility values in four-different molar ratios of camphor and menthol-based natural deep eutectic solvents (NADES) (1:0.65, 1:0.97, 1:1.47 & 1:2.25) at 0.1 MPa atmospheric pressure and five-diverse temperature conditions [T = (298.15, 300.65, 303.15, 305.65 & 308.15) K], (2) to validate the experimentally obtained cinnarizine's solubility values with various empirical and local composition models and (3) to determine the thermodynamic properties of cinnarizine solubility in camphor and menthol-based NADES. In a preliminary pilot study, the solubility of cinnarizine was checked in different NADES-forming excipients such as camphor, capric acid, lauric acid, menthol and thymol at various molar ratios. At 1:0.97 molar ratio of camphor and menthol, the mole fraction solubility value of drug was augmented up to 4.6847 × 10−3 at 298.15 K in comparison to the other tested NADES-forming excipients. The highest cinnarizine's mole fraction solubility was obtained in 1:0.97 molar ratio of camphor and menthol NADES at 308.15 K with a value of 19.5207 × 10−3, while the lowest value (1.8 × 10−3) was obtained in 1:0.67 ratio of camphor and menthol NADES at 298.15 K. Solubility correlation results show that the modified Jouyban-Acree model was best-fitted as it was obtained with the lowest absolute average deviation percent and absolute relative deviation percent values. The findings of dissolution thermodynamic of cinnarizine in NADESs composed of camphor and menthol indicate that the cinnarizine dissolution in camphor and menthol-based NADESs is enthalpy-driven. Eutecticity could be of an effective strategy to overcome cinnarizine's obstacle during drug delivery system development.