Solubility of ciprofloxacin in different solvents at several temperatures: Measurement, correlation, thermodynamics and Hansen solubility parameters

Ciprofloxacin is a commonly prescribed antibiotic drug whose solubility has not yet been completely studied. In this research, its equilibrium solubility at temperatures from T = (278.15 to 318.15) K in 13 neat solvents, namely, namely: 1,4-dioxane, polyethylene glycol (PEG) 600, PEG400, PEG300, N-methyl-2-pyrrolidone (NMP), PEG200, acetonitrile, N,N-dimethylformamide (DMF), ethanol, dimethyl sulfoxide (DMSO), methanol, ethylene glycol and water, is reported. Flask shake and UV–vis analysis were used for solubility determinations at different temperatures. Bottom solid phases were analyzed by DSC. Mole fraction solubility of ciprofloxacin (x2) increases when temperature arises in all solvents. It varies from x2 = 4.11 · 10–6 in neat water to x2 = 1.55 · 10–3 in neat PEG200 at T = 298.15 K. Solubility behavior was adequately correlated by van't Hoff, van't Hoff-Yaws and Apelblat model. From the variation of solubility with temperature the apparent thermodynamic analysis of dissolution was performed in all the solvents. Total Hildebrand solubility parameter of ciprofloxacin (δ2) was calculated based on groups’ contributions by means of both the Fedors and the Hoftyzer-van Krevelen methods as δ2 = (26.4 and 25.7) MPa1/2, respectively. Otherwise, Hansen solubility parameters and total Hildebrand solubility parameter were also determined by using the Bustamante method from experimental solubility values in 16 neat solvents obtaining δ2 = 25.2 MPa1/2. Finally, KAT-LSER model was also employed to evaluate the role of different intermolecular interactions on the dissolution of ciprofloxacin.