Display options
Cite
Ranjan S, Devarapalli R, Kundu S, et al. Isomorphism: 'molecular similarity to crystal structure similarity' in multicomponent forms of analgesic drugs tolfenamic and mefenamic acid. IUCrJ. 2020;7:173-183doi: 10.1107/S205225251901604X.
Ranjan, S., Devarapalli, R., Kundu, S., Saha, S., Deolka, S., Vangala, V. R., & Reddy, C. M. (2020). Isomorphism: 'molecular similarity to crystal structure similarity' in multicomponent forms of analgesic drugs tolfenamic and mefenamic acid. IUCrJ, 7173-183. https://doi.org/10.1107/S205225251901604X
Ranjan, Subham, et al. "Isomorphism: 'molecular similarity to crystal structure similarity' in multicomponent forms of analgesic drugs tolfenamic and mefenamic acid." IUCrJ vol. 7 (2020): 173-183. doi: https://doi.org/10.1107/S205225251901604X
Ranjan S, Devarapalli R, Kundu S, Saha S, Deolka S, Vangala VR, Reddy CM. Isomorphism: 'molecular similarity to crystal structure similarity' in multicomponent forms of analgesic drugs tolfenamic and mefenamic acid. IUCrJ. 2020 Jan 07;7:173-183. doi: 10.1107/S205225251901604X. eCollection 2020 Mar 01. PMID: 32148846; PMCID: PMC7055380.
Copy Download .nbib Format: NLM
Share it on

IUCrJ. 2020 Jan 07;7:173-183. doi: 10.1107/S205225251901604X. eCollection 2020 Mar 01.

Isomorphism: 'molecular similarity to crystal structure similarity' in multicomponent forms of analgesic drugs tolfenamic and mefenamic acid.

IUCrJ

Subham Ranjan, Ramesh Devarapalli, Sudeshna Kundu, Subhankar Saha, Shubham Deolka, Venu R Vangala, C Malla Reddy

Affiliations

  1. Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER), Kolkata, Mohanpur Campus, Mohanpur 741 246, India.
  2. Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835 215, India.
  3. Centre for Pharmaceutical Engineering Science, School of Pharmacy and Medical Sciences, University of Bradford, Richmond Road, Bradford BD7 1DP, UK.

PMID: 32148846 PMCID: PMC7055380 DOI: 10.1107/S205225251901604X

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-di-methyl-amino-pyridine (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 di-methyl-formamide (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.

© Ranjan et al. 2020.

Keywords: co-crystals; crystal engineering; isomorphism; polymorphism

References

  1. Chemistry. 2017 Apr 6;23(20):4936-4943 - PubMed
  2. Chemistry. 2006 Mar 1;12(8):2222-34 - PubMed
  3. Chem Commun (Camb). 2002 Jun 21;(12):1304-5 - PubMed
  4. IUCrJ. 2013 Oct 01;1(Pt 1):8-18 - PubMed
  5. Pharm Res. 2006 Oct;23(10):2375-80 - PubMed
  6. Acta Crystallogr A Found Adv. 2015 Jan;71(Pt 1):3-8 - PubMed
  7. Pharm Res. 2001 Jun;18(6):859-66 - PubMed
  8. J Am Chem Soc. 2018 May 23;140(20):6361-6373 - PubMed
  9. Acta Crystallogr B Struct Sci Cryst Eng Mater. 2016 Dec 1;72(Pt 6):836-845 - PubMed
  10. J Am Chem Soc. 2009 Apr 8;131(13):4554-5 - PubMed
  11. Acta Crystallogr B. 2004 Oct;60(Pt 5):547-58 - PubMed
  12. Acta Crystallogr C Struct Chem. 2015 Jan;71(Pt 1):3-8 - PubMed
  13. Chem Commun (Camb). 2006 May 28;(20):2123-5 - PubMed
  14. Acc Chem Res. 2018 Nov 20;51(11):2957-2967 - PubMed
  15. Annu Rev Phys Chem. 2015 Apr;66:21-42 - PubMed
  16. Angew Chem Int Ed Engl. 2013 Jun 17;52(25):6468-71 - PubMed
  17. Chem Commun (Camb). 2018 Jun 14;54(49):6348-6351 - PubMed
  18. J Am Chem Soc. 2016 Oct 19;138(41):13561-13567 - PubMed
  19. Drug Discov Today. 2008 Mar;13(5-6):198-210 - PubMed
  20. Acta Crystallogr A. 2008 Jan;64(Pt 1):112-22 - PubMed
  21. Acta Crystallogr B. 1999 Dec 1;55(Pt 6):1099-1108 - PubMed
  22. Chemistry. 2009;15(6):1508-15 - PubMed
  23. J Am Chem Soc. 2017 Feb 8;139(5):1975-1983 - PubMed

Publication Types