SOLUBILITIES OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS IN SUPERCRITICAL CARBON DIOXIDE

摘要

To develop micronization technique for pharmaceutical materials with the rapid expansion of supercritical solution (RESS) method, we need the solubility data of the substances of interest in supercritical fluids. In the present study, the solubility data of two fluorinated and non-steroidal anti-inflammatory drugs (NSAIDs) (flufenamic acid, CAS No. 530-78-9 and niflumic aicd, CAS No. 4394-00-7) in supercritical carbon dioxide were measured with a semi-flow type phase equilibrium apparatus at temperatures ranging from 313.2 K to 353.2 K and pressures up to 31 MPa. The solubilities can be as high as 2.13×10~(-4) and 2.09×10~(-5) in mole fraction for flufenamic acid and niflumic acid, respectively, at their highest equilibrium temperature and pressure. The saturated solubility data were correlated with the Charstil and the Mendez-Santiago-Teja equations. The Chrastil model fitted the experimental data to about within the experimental uncertainty. The correlated results of the Mendez-Santiago-Teja model endorsed the consistency of the solubility data over the entire experimental conditions. The results of this study are useful in the development of micronization process with the RESS method for these two pharmaceutical substances.