Determination, correlation and prediction of the solubilities of niflumic acid, clofenamic acid and tolfenamic acid in supercritical CO2

Abstract

In this paper, the solubilities of niflumic acid, clofenamic acid and tolfenamic acid were experimentally determined and correlated with the semi-empirical models. Meanwhile, their solubilities were also correlated and estimated using the compressed gas model combined with the reference solubilities and the modified expanded liquid model combined with the group contribution method. In solubility determination, the dynamic method was adopted and the solubilities under the pressures and temperatures of 12–36MPa and 313–333K were measured. The semi-empirical models containing Teja model, Chrastil model, Bartle model and Kumar–Johnston (K–J) model were used to correlate the solubilities of these fenamate medicines and the correlation results show a good consistency with the measured solubilities. The solubilities of the three fenamate medicines in sc-CO2 were correlated and estimated using the compressed gas model. With the experimental reference solubilities known, their solubilities can be correlated and predicted satisfactorily. The average absolute relative deviations (AARD%) are 5.0% and 11.9% respectively. Using the modified expanded liquid model, the solubilities of the three fenamate medicines were correlated and the average AARD% is 9.6%. Combined with the group contribution method, this model can estimate the solubilities of the three fenamate medicines in the order of magnitude.