title: Prediction of pharmaceutical solubility Via NRTL-SAC and COSMO-SAC.
abstract: Solid phase solubility is a fundamental parameter in the design of crystallization processes. The development and optimization of crystallization processes requires screening of numerous solvent systems for which the solubility of the compound of interest has to be measured as a function of temperature and solvent composition. Tools that quickly estimate the solubility in different solvents can be very useful in the initial phases of the solvent system selection process. In this paper, we report our experience applying two thermodynamic models in the solubility estimation of pharmaceutical compounds: the NRTL-SAC method (Chen and Song, 2004, Ind Eng Chem Res 43: 8354) which provides a correlative and predictive model from limited solubility measurements, and the COSMO-SAC (Lin and Sandler, 2002, Ind Eng Chem Res 41: 899) method which predicts solubility from ab initio calculations. These theoretical methods, coupled with rapid experimental measurement for verification, provide a powerful solubility screening protocol for the development of crystallization processes.
authors.affiliation: Merck Research Laboratories, 127 E Lincoln Ave., Rahway, New Jersey 07065, USA. Hsien_Hsin_Tung@Merck.com
authors.forename: Hsien-Hsin
authors.initials: HH
authors.lastname: Tung
authors.forename: Jose
authors.initials: J
authors.lastname: Tabora
authors.forename: Nara
authors.initials: N
authors.lastname: Variankaval
authors.forename: Daniel
authors.initials: D
authors.lastname: Bakken
authors.forename: Chau-Chyun
authors.initials: CC
authors.lastname: Chen
mesh_terms: D003460:Crystallization; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D012997:Solvents; D013696:Temperature; D013816:Thermodynamics