Solid liquid equilibrium of an antifungal drug itraconazole in different neat solvents: Determination and correlation

Abstract

The information regarding thermodynamic parameters on solid-liquid equilibrium (SLE) of itraconazole (ITR) in different neat solvents is essential for its pharmaceutical and industrial applications. The SLE of ITR in different neat solvents had not been studied previously in literature. Hence, in this study, the SLE of ITR in various neat solvents including “water, ethanol, isopropanol (IPA), ethylene glycol (EG), propylene glycol (PG), n-butanol, ethyl acetate (EA), dimethyl sulfoxide (DMSO), polyethylene glycol-400 (PEG-400) and Transcutol®” was determined and correlated at temperatures “T=298.2K to 318.2K” and pressure “p=0.1MPa”. The experimental solubilities of ITR in mole fraction were determined by shake flask method and correlated with “Van't Hoff and Apelblat models”. The measured solubility values of ITR in mole fraction were correlated well with “Van't Hoff and Apelblat models” with root mean square deviation values of <5.0%. The mole fraction solubility values of ITR were increasing with increase in temperature in all neat solvents investigated. The solubility of ITR was obtained highest in Transcutol (9.80×10−4) followed by DMSO (8.79×10−4), PEG-400 (4.62×10−4), EA (3.35×10−4), ethanol (4.84×10−5), n-butanol (4.46×10−5), IPA (3.58×10−5), PG (2.12×10−5), EG (9.85×10−6) and water (8.12×10−8) at T=318.2K. The solubilities of ITR were obtained in similar magnitude in Transcutol and DMSO, PEG-400 and EA and ethanol, IPA and n-butanol. The results of “apparent thermodynamic analysis” showed an “endothermic and entropy-driven dissolution” of ITR in each solvent evaluated.