Case, DH;
Srirambhatla, VK;
Guo, R;
Watson, RE;
Price, LS;
Polyzois, H;
Cockcroft, JK;
... Price, SL; + view all
(2018)
Successful computationally-directed templating of metastable pharmaceutical polymorphs.
Crystal Growth and Design
, 18
(9)
pp. 5322-5331.
10.1021/acs.cgd.8b00765.
Preview |
Text
Case_Successful.pdf - Published Version Download (4MB) | Preview |
Preview |
Text (Supporting information)
Price_FenematesSupporting InformationRevFin.pdf - Published Version Download (2MB) | Preview |
Abstract
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 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.
| Type: | Article |
|---|---|
| Title: | Successful computationally-directed templating of metastable pharmaceutical polymorphs |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acs.cgd.8b00765 |
| Publisher version: | http://dx.doi.org/10.1021/acs.cgd.8b00765 |
| Language: | English |
| Additional information: | This is an open access article published under a Creative Commons Attribution (CC-BY) License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10055976 |
Archive Staff Only
 |
View Item |
