Investigation of COSMO-SAC model for solubility and cocrystal formation of pharmaceutical compounds

Abstract

In this study, a predictive model named COSMO-SAC was investigated in solid/liquid equilibria for pharmaceutical compounds. The examined properties were the solubility of drug in the pure and mixed solvents, octanol/water partition coefficient, and cocrystal formation. The results of the original COSMO-SAC model (COSMO-SAC (2002)) was compared with a semi-predictive model named Flory–Huggins model and a revised version of the COSMO-SAC (COSMO-SAC (2010)). The results indicated the acceptable accuracy of the COSMO-SAC (2002) in the considered scope. The results emphasized on the suitability of the COSMO-SAC model for simple molecules containing C, H, and O by covalent and hydrogen bonding interactions. Applicability of the COSMO-SAC for more complicated molecules made of various functional groups such as COO and COOH doubly requires more modification in the COSMO-SAC.

A predictive PC-SAFT EOS based on COSMO for pharmaceutical compounds

“…The root-mean-square-error (RMSE) based on logarithmic scale for the predictive PC-SAFT EOS was 1.435. The calculated RMSE for the predictive PC-SAFT EOS was less than the reported RMSE (4.389) for COSMO-SAC by Mahmoudabadi and Pazuki 16 . The RMSEs for COSMO-RS model was 1.412.…”

“…The predictive PC-SAFT EOS was of object in the current study. The COSMO-SAC results were derived from Mahmoudabadi and Pazuki 16 . The COSMO-RS results were obtained in this study utilizing COSMOtherm software.…”

“…Furthermore, default atomic radii inputs to software based on COSMO calculations have certain uncertainty and also the flexibility to justify their values in an approach similar to that suggested by Van Nhu et al 23

Figure 5 . (a) Parity plot of experimental solubility data (mole fraction) in pure solvents compared to calculated solubility data (mole fraction) from predictive PC-SAFT EOS results (b) Parity plot of experimental solubility data (mole fraction) in pure solvents compared to calculated solubility data (mole fraction) from COSMO-SAC model 16 .

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“…In Eq. 24 , the sigma distribution is computed based on the method outlined by Mahmoudabadi and Pazuki 16 . The default values of the mentioned constants were reported in Klamt et al 35 .…”

“…The activity coefficient models based on COSMO, such as COSMO-RS 5 – 7 and COSMO-SAC 8 , have been known as successful tools in thermodynamic scope. Studies by Tung et al 9 , Zhou et al 10 , Paese et al 11 , Xavier et al 12 , Bouillot et al 13 , Shu and Lin 14 , Buggert et al 15 , and Mahmoudabadi and Pazuki 16 are some examples. Despite the remarkable characteristic of COSMO-based model, the vapor–liquid equilibria in COSMO-based model are computed by ideal gas assumption for vapor phase.…”