(261h) A Predictive Model to the Drug Solubility in Supercritical Carbon Dioxide

In this research, we examined the prediction of drug solubility in supercritical carbon dioxide from a predictive Peng-Robison plus COSMOSAC equation of state (PR+COSMOSAC EOS). The melting temperature, T_m and enthalpy, H_m, of the solid drug and the critical properties (Tc,Pc) and acentric factor for fluid are needed for the solubility predictions. The average logrithmetic deviations (ALD-x) in predicted solubility of 46 drugs in subcritical and supercritical carbon dioxide (T= 293.15 K~473K, P= 8.5MPa~50MPa, and 1150 solubility data ranging from 10^-7~10^-2) is found to be 1.14(1280%). The prediction inaccuracy can be significantly reduced to 0.75(462%) when introducing an additional correction to the dispersion energy for aromatic and ring structures. The stability of predicted solubility is further examined by the calculation of solid-liquid-vapor three-phase coexisting curve. To test the generality of the predictive method, the solid solubility in a variety of solvents (60 solids including 34 different solvents (with different polarities) and 190 drug-solvent pairs) at ambient pressure was also examined. The ALD-x was found to be 0.59(2890%) which is comparable to other prediction model, ex: COSMO-SAC (0.68,379%). The solid sublimation pressure was also examined. The ALD-x for the 32 solids (10 aromatic rings, 16 rings with polar functional group and 6 linear compounds) is 0.70(401%) which shows significantly improvement from the original PR+COSMOSAC EOS (1.30,1895%). The modified PR+COSMOSAC EOS is thus a useful tool for a priori prediction of solid solubility in scCO2, as well as for other solvents and other solid physical properties.