### Abstract

The concept of solubility parameter, which is widely used for the screening of solvents in pharmaceutical applications, is combined with a thermodynamic theory that is able to model systems with large deviations from ideal behavior. The nonrandom hydrogen-bonding (NRHB) theory is applied to model the phase behavior of mixtures of six Pharmaceuticals (i.e., ibuprofen, ketoprofen, naproxen, benzoic acid, methyl paraben, and ethyl paraben). The pure fluid parameters of the studied Pharmaceuticals were estimated using limited available experimental (or predicted) data on sublimation pressures, liquid densities, and Hansen's solubility parameters. The complex hydrogen-bonding behavior was explicitly accounted for, while the corresponding parameters were adopted from simpler molecules of similar chemical structure or/and fitted to the aforementioned pure fluid properties. In this way, the solubility of the studied Pharmaceuticals in liquid solvents was calculated. The average root-mean-square deviation between experimental and calculated solubilities is 0.190 and 0.037 in logio units for prediction (calculations without a binary interaction parameter adjustment) and for correlation (calculations using one binary interaction parameter fitted to experimental data), respectively. In addition, using one temperature-independent binary interaction parameter the phase behavior of Pharmaceuticals in supercritical CO_{2} and ethane was satisfactorily correlated. Finally, preliminary encouraging results are shown concerning two ternary mixtures where the model is able to predict accurately the solubility of Pharmaceuticals in mixed solvents based on interaction parameters fitted to corresponding single solvent data.

Original language | English |
---|---|

Pages (from-to) | 6446-6458 |

Number of pages | 13 |

Journal | Journal of Physical Chemistry B |

Volume | 113 |

Issue number | 18 |

DOIs | |

Publication status | Published - 7 May 2009 |

Externally published | Yes |

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### ASJC Scopus subject areas

- Physical and Theoretical Chemistry
- Materials Chemistry
- Surfaces, Coatings and Films

### Cite this

*Journal of Physical Chemistry B*,

*113*(18), 6446-6458. https://doi.org/10.1021/jp807952v

**Modeling the phase behavior in mixtures of pharmaceuticals with liquid or supercritical solvents.** / Tsivintzelis, Ioannis; Economou, Ioannis; Kontogeorgis, Georgios M.

Research output: Contribution to journal › Article

*Journal of Physical Chemistry B*, vol. 113, no. 18, pp. 6446-6458. https://doi.org/10.1021/jp807952v

}

TY - JOUR

T1 - Modeling the phase behavior in mixtures of pharmaceuticals with liquid or supercritical solvents

AU - Tsivintzelis, Ioannis

AU - Economou, Ioannis

AU - Kontogeorgis, Georgios M.

PY - 2009/5/7

Y1 - 2009/5/7

N2 - The concept of solubility parameter, which is widely used for the screening of solvents in pharmaceutical applications, is combined with a thermodynamic theory that is able to model systems with large deviations from ideal behavior. The nonrandom hydrogen-bonding (NRHB) theory is applied to model the phase behavior of mixtures of six Pharmaceuticals (i.e., ibuprofen, ketoprofen, naproxen, benzoic acid, methyl paraben, and ethyl paraben). The pure fluid parameters of the studied Pharmaceuticals were estimated using limited available experimental (or predicted) data on sublimation pressures, liquid densities, and Hansen's solubility parameters. The complex hydrogen-bonding behavior was explicitly accounted for, while the corresponding parameters were adopted from simpler molecules of similar chemical structure or/and fitted to the aforementioned pure fluid properties. In this way, the solubility of the studied Pharmaceuticals in liquid solvents was calculated. The average root-mean-square deviation between experimental and calculated solubilities is 0.190 and 0.037 in logio units for prediction (calculations without a binary interaction parameter adjustment) and for correlation (calculations using one binary interaction parameter fitted to experimental data), respectively. In addition, using one temperature-independent binary interaction parameter the phase behavior of Pharmaceuticals in supercritical CO2 and ethane was satisfactorily correlated. Finally, preliminary encouraging results are shown concerning two ternary mixtures where the model is able to predict accurately the solubility of Pharmaceuticals in mixed solvents based on interaction parameters fitted to corresponding single solvent data.

AB - The concept of solubility parameter, which is widely used for the screening of solvents in pharmaceutical applications, is combined with a thermodynamic theory that is able to model systems with large deviations from ideal behavior. The nonrandom hydrogen-bonding (NRHB) theory is applied to model the phase behavior of mixtures of six Pharmaceuticals (i.e., ibuprofen, ketoprofen, naproxen, benzoic acid, methyl paraben, and ethyl paraben). The pure fluid parameters of the studied Pharmaceuticals were estimated using limited available experimental (or predicted) data on sublimation pressures, liquid densities, and Hansen's solubility parameters. The complex hydrogen-bonding behavior was explicitly accounted for, while the corresponding parameters were adopted from simpler molecules of similar chemical structure or/and fitted to the aforementioned pure fluid properties. In this way, the solubility of the studied Pharmaceuticals in liquid solvents was calculated. The average root-mean-square deviation between experimental and calculated solubilities is 0.190 and 0.037 in logio units for prediction (calculations without a binary interaction parameter adjustment) and for correlation (calculations using one binary interaction parameter fitted to experimental data), respectively. In addition, using one temperature-independent binary interaction parameter the phase behavior of Pharmaceuticals in supercritical CO2 and ethane was satisfactorily correlated. Finally, preliminary encouraging results are shown concerning two ternary mixtures where the model is able to predict accurately the solubility of Pharmaceuticals in mixed solvents based on interaction parameters fitted to corresponding single solvent data.

UR - http://www.scopus.com/inward/record.url?scp=66349123569&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66349123569&partnerID=8YFLogxK

U2 - 10.1021/jp807952v

DO - 10.1021/jp807952v

M3 - Article

VL - 113

SP - 6446

EP - 6458

JO - Journal of Physical Chemistry B Materials

JF - Journal of Physical Chemistry B Materials

SN - 1520-6106

IS - 18

ER -