Solid Solubilities of Sulfonamides and Use of Rapid Expansion of Supercritical Solutions for Microparticle Production

The solubility of solid active pharmaceutical ingredients in supercritical fluids is a major thermodynamic criterion for selection and screening of microparticle generation processes. To develop an efficient method for solubility prediction, a solution model was adopted to establish the correlations of the solid solubilities of six sulfonamides in supercritical CO 2 . The model was capable of determining solubility correlations. Accordingly, it was attempted to simplify and generalize the model, yielding a predictive solution model, which provided order‐consistent solubility predictions. A case study for model extrapolation was conducted. After understanding the mechanisms underlying the solubility of sulfonamides, the rapid expansion of supercritical solutions (RESS) process was applied to produce microparticles of p ‐toluenesulfonamide, an anticancer drug. The effects of RESS process parameters were investigated.