A strategy of using crystal structure prediction (CSP) methods to determine which, if any, isostructural template could facilitate the first crystallization of a predicted polymorph by vapor deposition is extended to the fenamate family. Mefenamic acid (MFA) and tolfenamic acid (TFA) are used as molecules with minimal chemical differences, whereas flufenamic acid (FFA) shows greater differences in the substituents. The three crystal energy landscapes were calculated, and periodic electronic structure calculations were used to confirm the thermodynamic plausibility of possible isostructural polymorphs to experimentally obtainable crystals of the other molecules. As predicted, a new polymorph, TFA form VI, was found by sublimation onto isomorphous MFA form I, using a recently developed technique. MFA and TFA form a continuous solid solution with the structure of MFA I and TFA VI at the limits, but the isomorphous MFA/FFA solid solution does not extended to a new polymorph of FFA. The novel solid solution structure of TFA and FFA was found, and a new isomorphous polymorph TFA VII was found by sublimation onto this new solid solution template. Sublimation of TFA onto a metal surface at the early stage of deposition gave TFA form VIII. We rationalize the formation of new polymorphs of only TFA.

Presentation and applied case study of a system-wide workflow which supports rapid, systematic and efficient continuous seeded cooling crystallisation process design, with the aim to deliver a robust, consistent process with tight control of particle attributes.

A new method of inducing the crystallisation of metastable polymorphs by isomorphous templating has been developed and used to reproduce the crystallisation of CBZ-V on the surface of DHC-II. Studies of the growth of CBZ-V on DHC-II single crystals show crystals growing laterally and vertically on DHC-II surfaces without any significant face selectivity. The generality of this computationally inspired crystallisation approach is demonstrated by producing the first crystals of an entirely new polymorph of cyheptamide, which is isomorphous to both DHC-II and CBZ-V.