Toward Physics-Based Solubility Computation for Pharmaceuticals to Rival Informatics
Daniel J. Fowles, David Scott Palmer, Rui Guo, Sarah L. Price, John B. O. Mitchell
Abstract
method leads to accurate estimates of sublimation free energy. Combining these with hydration free energies obtained from either molecular dynamics free-energy perturbation simulations or density functional theory calculations, solubilities comparable to both experiment and informatics predictions are obtained. The application to coronene, succinic acid, and the pharmaceutical desloratadine shows how the methods must be adapted for the adoption of different conformations in different phases. The approach has the flexibility to extend to applications that cannot be covered by informatics methods.
Topics & Concepts
Sublimation (psychology)Statistical physicsPiecewiseComputationCheminformaticsPhononChemistryThermodynamicsPhysicsComputer scienceComputational chemistryAlgorithmQuantum mechanicsMathematicsPsychotherapistMathematical analysisPsychologyComputational Drug Discovery MethodsCrystallography and molecular interactionsCrystallization and Solubility Studies