Since allantoin is an active ingredient in skin creams production for skin wounds treatment and skin cares, its solubility was studied in supercritical CO2 as a clean and efficient technique. Two significant independent variables involving pressure (200–500 bar) and temperature (30–60 ◦C) effect on the allantoin solubility with using ethanol (as a polar cosolvent) were studied. Therefore, Central Composite Design (CCD) under Response Surface Methodology (RSM) was applied to design the experiments. 13 experiments with their operating conditions were proposed by the software. According to the experiments, the optimum solubility of allantoin (0.003745) was found at pressure of 202 bar and temperature of 51 ◦C while the maximum solubility (0.003677) was experimentally obtained at pressure of 200 bar and temperature of 60 ◦C in supercritical CO2. Furthermore, Mohsen-Nia-Modarress-Mansoori (MMM) equation of state, which is a proper equation for the biological molecules’ solubility prediction, was applied to find the allantoin solubility, thermodynamically. According to the calculated errors, a good agreement between experimental and modeled data was found. Finally, the binary coefficients were reported.
