Pressure drop particle precipitation from a quasi-incompressible, ternary and liquid mixture

Abstract We found a quasi-incompressible and liquid mixture of ibuprofen, water and acetone, that enables the crystallization of ibuprofen particles by decreasing the pressure from 15 MPa to ambient pressure ( ~ 0.1 MPa ) . We measured the solubility of ibuprofen in the mixture as a function of the acetone/water-ratio for pressures of 0.1 MPa , 5.5 MPa and 15 MPa and at 308 K using the cloud point method. Based on the solubilities, binodal compositions of the ternary system were modelled using the NRTL-SAC model. The solubility of the drug in the mixture increases with increasing pressure at constant acetone/water-ratio. This pressure sensitive solubility can be exploited for the crystallization of ibuprofen particles via a pressure-drop approach. A pressure-drop from 15 MPa to ambient pressure ~ 0.1 MPa can result in a supersaturation of up to 1.43 .