Model evaluation for the prediction of solubility of active pharmaceutical ingredients (APIs) to guide solid–liquid separator design

Publication date: May 2018Source: Asian Journal of Pharmaceutical Sciences, Volume 13, Issue 3Author(s): Kuveneshan Moodley, Jürgen Rarey, Deresh RamjugernathAbstractThe assumptions and models for solubility modelling or prediction in systems using non-polar solvents, or water and complex triterpene and other active pharmaceutical ingredients as solutes aren't well studied. Furthermore, the assumptions concerning heat capacity effects (negligibility, experimental values or approximations) are explored, using non-polar solvents (benzene), or water as reference solvents, for systems with solute melting points in the range of 306–528 K and molecular weights in the range of 90–442 g/mol. New empirical estimation methods for the ΔfusCpi of APIs are presented which correlate the solute molecular masses and van der Waals surface areas with ΔfusCpi. Separate empirical parameters were required for oxygenated and non-oxygenated solutes. Subsequently, the predictive capabilities of the various approaches to solubility modelling for complex pharmaceuticals, for which data is limited, are analysed. The solute selection is based on a principal component analysis, considering molecular weights, fusion temperatures, and solubilities in a non-polar solvent, alcohol, and water, where data was available. New NRTL-SAC parameters were determined for selected steroids, by regression. The original UNIFAC, modified UNIFAC (Dortmund), COSMO-RS (OL), and COSMO-SAC activity coefficient predi...
Source: Asian Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Source Type: research