Executive Director of Computational Chemistry and Data Science J-Star Research | Porton Ashland, Massachusetts
The screening of multicomponent crystal system (MCC) along salt-cocrystal continuum is a key method for improving physicochemical properties of active pharmaceutical ingredients (APIs). The goal of this study is to evaluate performance of the counterion screening methods and propose and validate novel approaches to virtual solvent screening for salt, cocrystal of salt, or cocrystal crystallization.
The actual performance of the ΔpKa rules for counterion selection for salt crystallization was validated using multiple screenings reports. Novel computational models for virtual solvent screening to avoid incongruent crystallization of MCCs (salt, cocrystal of salt, or cocrystal) were proposed. Using the ΔpKa>3 rule, 10 acid counterions were selected for experimental aripiprazole salt screening using 10 organic solvents. The experimental results were used to validate the proposed novel virtual solvent screen models. Proposed computational models can be easily applied to newly discovered APIs.
Learning Objectives:
The actual performance of the ΔpKa rules for counterion selection for salt crystallization.
Novel computational approaches for selection of organic solvents for salt, cocrystal of salt, or cocrystal crystallization.
New salt and cocrystal of salt forms of aripiprazole which were found by the combined computational and experimental screening