Loading...
Isomorphism: 'Molecular similarity to crystal structure similarity' in multicomponent forms of analgesic drugs tolfenamic and mefenamic acid
Ranjan, S. Devarapalli, R. Kundu, S. Saha, S. Deolka, S. Vangala, Venu R. Reddy, C.M.
Ranjan, S.
Devarapalli, R.
Kundu, S.
Saha, S.
Deolka, S.
Vangala, Venu R.
Reddy, C.M.
Publication Date
2020-03
End of Embargo
Supervisor
Rights
(c) 2020 The Authors. This is an Open Access article distributed under the Creative Commons CC-BY license (https://creativecommons.org/licenses/by/4.0/)
Peer-Reviewed
Yes
Open Access status
openAccess
Accepted for publication
2019-11-28
Institution
Department
Awarded
Embargo end date
Collections
Additional title
Abstract
The non-steroidal anti-inflammatory drugs mefenamic acid (MFA) and
tolfenamic acid (TFA) have a close resemblance in their molecular scaffold,
whereby a methyl group in MFA is substituted by a chloro group in TFA. The
present study demonstrates the isomorphous nature of these compounds in a
series of their multicomponent solids. Furthermore, the unique nature of MFA
and TFA has been demonstrated while excavating their alternate solid forms in
that, by varying the drug (MFA or TFA) to coformer [4-dimethylaminopyridine
(DMAP)] stoichiometric ratio, both drugs have produced three different types
of multicomponent crystals, viz. salt (1:1; API to coformer ratio), salt hydrate
(1:1:1) and cocrystal salt (2:1). Interestingly, as anticipated from the close
similarity of TFA and MFA structures, these multicomponent solids have shown
an isomorphous relation. A thorough characterization and structural investigation of the new multicomponent forms of MFA and TFA revealed their
similarity in terms of space group and structural packing with isomorphic nature
among the pairs. Herein, the experimental results are generalized in a broader
perspective for predictably identifying any possible new forms of comparable
compounds by mapping their crystal structure landscapes. The utility of such an
approach is evident from the identification of polymorph VI of TFA from
hetero-seeding with isomorphous MFA form I from acetone–methanol (1:1)
solution. That aside, a pseudopolymorph of TFA with dimethylformamide
(DMF) was obtained, which also has some structural similarity to that of the
solvate MFA:DMF. These new isostructural pairs are discussed in the context of
solid form screening using structural landscape similarity
Version
Published version
Citation
Ranjan S, Devarapalli R, Kundu S et al (2020) Isomorphism: 'Molecular similarity to crystal structure similarity' in multicomponent forms of analgesic drugs tolfenamic and mefenamic acid. IUCrJ. 7(2): 173-183.
Link to publisher’s version
Link to published version
Link to Version of Record
Type
Article