Optimal thermodynamic conditions for ternary system (CO2, DMSO, ampicillin) in supercritical CO2 antisolvent process

• Optimum conditions for DMSO–CO2–ampicillin system were investigated via modeling.
• Peng–Robinson equation with linear combination of Vidal–Michelsen mixing rules was used.
• Modeling data can be used in production of ampicillin nanoparticles by GAS process.
• 95% ampicillin production occurred above 7.3, 8, 8.97 MPa at 308, 313 and 319 K.

Pharmaceutical micronization increases the dissolution rate and bioavailability absorption and thus decreases the dosage used. Conventional methods of micronization such as jet milling, spray drying and freeze drying have some drawbacks. Alternative methods, pharmaceutical micronization with supercritical fluids have recently attracted interest to overcome the shortcomings of conventional micronization methods. But the precipitation of particles in the supercritical gas antisolvent (GAS) process does not occur at arbitrary operating conditions. Thus thermodynamic models (phase equilibrium) are necessary to evaluate the suitable operating conditions in order to obtain the feasible application of GAS process. In this work the volume expansion and process conditions for the binary system (carbon dioxide (CO2) and dimethyl sulfoxide (DMSO)) and ternary system (CO2, DMSO, and ampicillin) were determined. The Peng–Robinson equation of state with linear combination of Vidal and Michelsen mixing rules (PR-LCVM) was used to model the fluid phases. The minimum pressures for ternary system at 308, 313 and 319 K were 7.3, 8, 8.97 MPa, respectively. At these operating pressures, recrystallization of the dissolved ampicillin occurred.