Abstract
The crystal and molecular structures of vardenafil (free, unprotonated base), vardenafil dihydrate and the hydrochloride salts, vardenafil monohydrochloride trihydrate and vardenafil dihydrochloride hexahydrate, were determined by single-crystal X-ray diffraction. The crystal structure of vardenafil monohydrochloride trihydrate is in good agreement with the published crystal structure obtained by powder diffraction using synchrotron radiation. This work shows that the crystal structure of anhydrous vardenafil free base is very similar to the crystal structure of sildenafil free base.
Acknowledgment
The authors would like to thank Dr. Steve Cook for reviewing the article and for his valuable comments.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
References
1. Rotella, D. Nat. Rev. Drug Discov. 2002, 1, 674–682; https://doi.org/10.1038/nrd893.Search in Google Scholar PubMed
2. Levitra® Drug Product Insert. Available at https://gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Brands/LEVITRA/pdf/LEVITRA_PI.PDF (accessed year 2020).Search in Google Scholar
3. Wheatly, A., Kaduk, J., Gindhart, A., Blanton, T. Powder Diffr. 2018, 33, 319–326.10.1017/S0885715618000696Search in Google Scholar
4. Szramka, R., Drygas, J., Szulc, M., Rynkiewicz, R. The Methods for Manufacturing of Vardenafil and its Salts. Pub. No.: US 2016/0311827 A1, October 27, 2016.Search in Google Scholar
5. Sajja, E., Koppera, R., Revu, S., Vajrala, V., Kanumathi, V. Polymorphic Forms of Vardenafil. Pub. No.: US 2007/0197535 A1, August 23, 2007.Search in Google Scholar
6. Niewohner, U., Es-Sayed, M., Haning, H., Schlemmer, K., Keldenich, J., Bischoff, E., Perzborn, E., Dembowsky, K., Serno, P., Nowakowski, M. 2-Phenyl Substituted Imidazotriazinones as Phosphodiesterase Inhibitors. Patent No.: US 6,362,178 B1, March 26, 2002.Search in Google Scholar
7. Jayaraman, R., Panchasara, D., Prajapati, B., Shah, P., Shah, A. Novel Crystalline Form of Vardenafil Base. IN3769MU2013 (A), July 31, 2015.Search in Google Scholar
8. Groom, C. R., Bruno, I. J., Lightfoot, M. P., Ward, S. C. Acta Crystallogr. 2016, B72, 171–179; https://doi.org/10.1107/s2052520616003954.Search in Google Scholar
9. Cambridge Structural Database (CSD) (Version 5.41, November 2019; CSD Release 2020.1); The Cambridge Crystallographic Data Centre (CCDC): Cambridge (U.K.), 2020. A list of the CSD Refcodes and the bibliographic information of these structure determinations is given as Supporting Information available online.Search in Google Scholar
10. Sheldrick, G. M. Shelxl-97, Program for the Refinement of Crystal Structures; University of Göttingen: Göttingen (Germany), 1997.Search in Google Scholar
11. Serno, P., Grunenberg, A., Ohn, A., Bellinghausen, R., Vollers, E., Henck, J.-O. Medicaments Containing Vardenafil Hydrochloride Trihydrate. US 8,273,876 B2, September 25, 2012.Search in Google Scholar
12. Stepanovs, D., Mishnev, A. Z. Naturforsch. 2012, 67b, 491–494; https://doi.org/10.5560/znb.2012-0073.Search in Google Scholar
13. Barbas, R., Font-Bardia, M., Prohens, R. Cryst. Growth Des. 2018, 18, 3740–3746; https://doi.org/10.1021/acs.cgd.8b00683.Search in Google Scholar
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/znb-2020-0083).
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