Diversity of felodipine solvates: Structure and physicochemical properties

Solvates of the calcium-channel blocking agent felodipine with three structurally related common organic solvents, acetone (ATN), dimethyl sulfoxide (DMSO) and acetophenone (APN), are described. A relationship between the felodipine packing arrangement in all known solvates and the van der Waals volume of the solvent molecule is established. Intermolecular interaction energies in the crystals are examined using the PIXEL approach in order to rationalize the difference between alternative molecule packing arrangements. DSC studies show that the desolvation onset temperatures of the solvates are closely comparable, despite the large difference in the boiling points of the solvent molecules. The enthalpies of formation derived from the calorimetric data for the solvates are also found to be similar, despite the difference in the van der Waals volume of the solvent molecules.This work was supported by a grant from the President of the Russian Federation no. МК- 67.2014.3 and Russian Foundation for Basic Research (project № 14-03-31001).This is the accepted manuscript. The final version is available at http://pubs.rsc.org/en/Content/ArticleLanding/2015/CE/C5CE00350D#!divAbstract

The influence of solid state information and descriptor selection on statistical models of temperature dependent aqueous solubility.

Predicting the equilibrium solubility of organic, crystalline materials at all relevant temperatures is crucial to the digital design of manufacturing unit operations in the chemical industries. The work reported in our current publication builds upon the limited number of recently published quantitative structure-property relationship studies which modelled the temperature dependence of aqueous solubility. One set of models was built to directly predict temperature dependent solubility, including for materials with no solubility data at any temperature. We propose that a modified cross-validation protocol is required to evaluate these models. Another set of models was built to predict the related enthalpy of solution term, which can be used to estimate solubility at one temperature based upon solubility data for the same material at another temperature. We investigated whether various kinds of solid state descriptors improved the models obtained with a variety of molecular descriptor combinations: lattice energies or 3D descriptors calculated from crystal structures or melting point data. We found that none of these greatly improved the best direct predictions of temperature dependent solubility or the related enthalpy of solution endpoint. This finding is surprising because the importance of the solid state contribution to both endpoints is clear. We suggest our findings may, in part, reflect limitations in the descriptors calculated from crystal structures and, more generally, the limited availability of polymorph specific data. We present curated temperature dependent solubility and enthalpy of solution datasets, integrated with molecular and crystal structures, for future investigations

Solvation and hydration characteristics of ibuprofen and acetylsalicylic acid

Ibuprofen and acetylsalicylic acid were studied by thermoanalytical methods: sublimation calorimetry, solution calorimetry, and with respect to solubility. Upon measuring the temperature dependences of the saturated vapor pressure, enthalpies of sublimation, ΔHsub0, as well as the entropies of sublimation, ΔHsub0, and their respective relative fractions in the total process were calculated. The Gibbs energy of solvation in aliphatic alcohols as well as the enthalpic and entropic fractions thereof were also studied and compared with the respective properties of model substances and other nonsteroidal antiinflammatory drugs (benzoic acid, diflunisal, flurbiprofen, ketoprofen, and naproxen). In all cases, enthalpy was found to be the driving force of the solvation process. Correlations were derived between Gibbs energy of solvation in octanol, ΔGsolvOct, and the transfer Gibbs energy from water to octanol, ΔGtr0. Influence of mutual octanol and water solubilities on the driving force of partitioning is discussed. An enthalpy-entropy-compensation effect in octanol was observed, and consequences of deviation from the general trend are also discussed