title: Benzoic Acid and Chlorobenzoic Acids: Thermodynamic Study of the Pure Compounds and Binary Mixtures With Water.
abstract: Benzoic acid is a model compound for drug substances in pharmaceutical research. Process design requires information about thermodynamic phase behavior of benzoic acid and its mixtures with water and organic solvents. This work addresses phase equilibria that determine stability and solubility. In this work, Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) was used to model the phase behavior of aqueous and organic solutions containing benzoic acid and chlorobenzoic acids. Absolute vapor pressures of benzoic acid and 2-, 3-, and 4-chlorobenzoic acid from literature and from our own measurements were used to determine pure-component PC-SAFT parameters. Two binary interaction parameters between water and/or benzoic acid were used to model vapor-liquid and liquid-liquid equilibria of water and/or benzoic acid between 280 and 413 K. The PC-SAFT parameters and 1 binary interaction parameter were used to model aqueous solubility of the chlorobenzoic acids. Additionally, solubility of benzoic acid in organic solvents was predicted without using binary parameters. All results showed that pure-component parameters for benzoic acid and for the chlorobenzoic acids allowed for satisfying modeling phase equilibria. The modeling approach established in this work is a further step to screen solubility and to predict the whole phase region of mixtures containing pharmaceuticals.
authors.affiliation: Laboratory of Thermodynamics, Department BCI, Technische Universität Dortmund, D-44227 Dortmund, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reschke
authors.affiliation: Nikolaev Institute of Inorganic Chemistry of Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
authors.forename: Kseniya V
authors.initials: KV
authors.lastname: Zherikova
authors.affiliation: Department of Physical Chemistry, University of Rostock, D-18059 Rostock, Germany; Department of Science and Technology of Life, Light and Matter, University of Rostock, D-18059 Rostock, Germany; Department of Physical Chemistry, Kazan Federal University, 420008 Kazan, Russia.
authors.forename: Sergey P
authors.initials: SP
authors.lastname: Verevkin
authors.affiliation: Laboratory of Thermodynamics, Department BCI, Technische Universität Dortmund, D-44227 Dortmund, Germany. Electronic address: christoph.held@bci.tu-dortmund.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Held
mesh_terms: D019817:Benzoic Acid / Q000737:chemistry*; D002723:Chlorobenzoates / Q000737:chemistry*; D004355:Drug Stability; D009930:Organic Chemicals / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D002723:Chlorobenzoates; D009930:Organic Chemicals; D012997:Solvents; D014867:Water; D019817:Benzoic Acid
keywords: activity coefficient; drug interactions; physicochemical properties; poorly water-soluble drugs; solubility; stability; statistical thermodynamics; thermodynamics