A rational coformer screening methodology was adopted to identify new multicomponent solid preformulations of the 2-aryl propionate class of nonsteroidal anti-inflammatory drugs. The coformer screening was performed using a modified molecular electrostatic potential based site−pair interaction energy computations used in conjunction with the free energy of cocrystal formation calculations to attain better predictability. The computational results were validated against the available experimental data and used for optimizing the cocrystal screening methodology for the drug zaltoprofen. A new polymorph and three new cocrystal forms of zaltoprofen were reported in the study, which exhibits up to four times enhancement in the drug solubility than that of the marketed form. We also report one new salt and two new cocrystals of (+)-ibuprofen, a drug from the same 2-aryl propionate family. In hindsight, we propose incorporating secondary heteromeric interactions formed by homo/heterodimer in the calculations of site−pair interaction energy differences for improving the predictability of the molecular electrostatic potential (MESP) based screening.

Computational studies of hydrogen-bonded cationic species observed in the synephrine salts point towards the stabilizing nature of hydrogen bonds and highlights their contribution in reducing destabilization caused by coulombic repulsion.

A structural landscape approach can be advantageous in the identification and assessment of the most probable polymorphs of a given compound. However, the experimental realization of these putative polymorphs remains a challenging endeavor. In this report, we present the utilization of a structural landscape study in the identification and characterization of a new polymorph (form III) of 4nitrobenzoic acid, which was obtained after 38 years. The reported polymorph was first predicted from the crystal structure prediction computation, then validated by the fluoro substitution method, and finally realized experimentally by utilizing the information deduced from the landscape study. Additionally, the role of crystallizing solvent in promoting the crystal growth of the new polymorph was studied using the Fourier transform infrared and fluorescence spectroscopic data, which sheds some light on the polymorph selection in the solution.