Penicillins' Solubility in Supercritical Carbon Dioxide: Modeling by Cubic Equations of States Revisited

Development of processes using green solvents as supercritical fluids (SCFs) depends on the accuracy of modeling and predicting phase equilibrium which is of considerable importance to exploit the use of SCF process at the level of pharmaceutical industries. Solid-Fluid equilibrium modeling is associated to many drawbacks when compressed gas-based models as cubic equations of states (cEoSs) are used. The unavailability of experimental values of solute's sublimation pressure presents one of the major obstacles to the solubility modeling with this type of models, and thus, its estimation is essential and inevitable. This work is an attempt to address a question regarding "accurate estimated value" of sublimation pressure of two antibiotics Penicillin G (benzyl penicillin) and Penicillin V (phenoxymethyl penicillin). Toward that, first, cEoSs are provided as the thermodynamics modeling framework and fundamental approach. Second, a discussion and a review of some literature results are given. Third, results are invoked to present a criticism analysis that comes from the use of modified form of Peng-Robinson (PR) equation of states. Finally, considerable improvement of modeling results by using a new sublimation pressure is shown.