(279f) Modelling the Thermodynamic Properties of Complex Organic Molecules of Pharmaceutical Interest With the SAFT-? Mie Group Contribution Approach

The accurate modelling of complex organic compounds typically present in systems of pharmaceutical interest is of great importance for the efficient design of drug processing and production. The major challenge in this case is the characterisation of these multifunctional compounds polar and apolar chemical moeties for which experimental data are often scarce. A number of correlative approaches have been presented, including work based on the PC-SAFT^[1] equation of state (EoS) and the NRTL-SAC method^[2]. Such approaches have prove successful in modelling of the solubility of active pharmaceutical ingredients (APIs) in pure and mixed solvents, though their applicability is limited since a significant amount of experimental solubility data is required for the parameterisation of the models. A way to overcome this limitation is the application of predictive thermodynamic methodologies, such as those based on activity coefficient models, e.g., COSMO-SAC^[3] and the UNIFAC^[4] methods. In this work we present the application of the group-contribution based SAFT-g EoS^[5,6] in the study of complex molecules, with a main focus on the use of the extension of the new methodology for Mie potentials^[7] to describe APIs. The advantage of using a predictive approach, such as the SAFT-g Mie EoS, is that the required parameters for the characterisation of the systems of interest are fully transferable and can thus be obtained by the study of "simpler" systems, for which experimental data is more readily available. No experimental information for the specific APIs under study are required for the parameterisation of the model. Our  SAFT-g Mie GC methodology is applied here for a range of APIs both in the study of the solubility of APIs in organic solvents and solvent mixtures, and the study of their partition coefficients in systems of solvents that form two or more liquid phases.

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[2] C.-C. Chen and P. A. Crafts, Ind. Eng. Chem. Res., 45 (2006), pp. 4816-4824

[3] C.-C. Shu and S.-T. Lin, Ind. Eng. Chem. Res., 50 (2011), pp. 142-147

[4] A. Diedrichs and J. Gmehling, Ind. Eng. Chem. Res., 50 (2011), pp. 1757-1769

[5] A. Lymperiadis, C. S. Adjiman, A. Galindo and G. Jackson, J. Chem. Phys., 127 (2007), p. 234903

[6] A. Lymperiadis, C. S. Adjiman, A. Galindo and G. Jackson, Fluid Phase Equilib., 274 (2008), pp. 85-104

[7] C. Avendano, T. Lafitte, C. S. Adjiman, A. Galindo, E. A. Muller and G. Jackson, J. Phys. Chem. B, 117 (2013), p. 2717