A predictive method for the solubility of drug in supercritical carbon dioxide

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• 作者：Li-Hsin Wang ; Shiang-Tai Lin
• 关键词：Peng&ndash ; Robinson equation of state ; COSMO-SAC ; Solubility ; Solvation free energy ; A priori prediction
• 刊名：The Journal of Supercritical Fluids
• 出版年：January, 2014
• 年：2014
• 卷：85
• 期：Complete
• 页码：81-88
• 全文大小：983 K

文摘

We present a predictive approach for the solubility of drug in supercritical CO₂. The fugacity of drug in the solid phase is estimated from its melting temperature and heat of fusion, and the fugacity of the drug in its hypothetical liquid state. The fugacity of the drug is calculated from the Peng-Robinson (PR) EOS. Temperature and composition dependence of the interaction parameters a(T,x) and b(x) of the PR EOS are obtained from the quantum mechanics-based, COSMO-SAC solvation model. As a consequence, the method does not require input of experimental data of the mixture. The average logarithmic deviation (ALD-x) in predicted solubility of 46 drugs in subcritical and supercritical carbon dioxide (T = 293.15-473 K, P = 8.5-50 MPa, and 1160 solubility data ranging from 10^鈭? to 10^鈭?) was found to be 0.81 (a factor of 5.3). The same method was also examined for solid solubility in a variety of solvents (60 solids including 34 different solvents (with different polarities) and 190 drug-solvent pairs) at ambient pressure. The ALD-x was found to be slightly better (0.58 or a factor of 2.89). The proposed method, the PR + COSMOSAC EOS, is thus a useful tool for a priori prediction of solid solubility in scCO₂, as well as for other solvents.