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 CO2. 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. A predictive solution model was developed to predict the solid solubility of sulfonamides in supercritical CO2. Microparticles of p‐toluenesulfonamide, an anticancer drug, with a mean size of 1.09 μm were successfully produced through an organic solvent‐free rapid expansion of supercritical solutions process. The effects of rapid expansion of supercritical solutions process parameters were evaluated.