Measurement, correlation and thermodynamic modeling of the solubility of Ketotifen fumarate (KTF) in supercritical carbon dioxide: Evaluation of PCP-SAFT equation of state

Solubility measurement of desired solid component(s) represents a primary and crucial step of feasibility study on production process of a nanoparticle drug through supercritical fluid (SCF) technology. Ketotifen fumarate (KTF) is an effective anti-histamine and anti-inflammatory drug with a wide spectrum of applications in treatment and prevention of a variety of mucosal and skin allergies. In this research, for the first time, solubility of KTF was determined experimentally in supercritical carbon dioxide (SC-CO2) at different temperatures in the range 308.2-338.2 K and different pressures in the range 120-300 bar. Obtained in mole fraction, KTF solubility was in the range of 0.211 x 10(-4) to 10.766 x 10(-4). To predict solubility of the solid solute drug in supercritical fluid, experimental data modeling was successfully accomplished by using two different groups of models, i.e. six density-based empirical models, namely Chrastil, Khansari, Bartle, Spark and Bian models, and two equations of state (EoS), namely PengRobinson (PR) and Perturbed-Chain Statistical Associating Fluid (PCP-SAFT). Results of analysis of variance (ANOVA) indicated the Peng-Robinson model as the model of choice for predicting solubility of KTF in SC-CO2. Using correlation results, the heat of drug-CO2 solvation and that of drug vaporization were approximated as 223.77 and 0.09577 kJ/mol, respectively. (C) 2017 Elsevier B.V. All rights reserved.