Тhe technology basis of diclofenac substance production

The basis of the production technology of the diclofenac substance, which consists of five main technological stages, is justified and proposed. The proposed technological aspects of diclofenac substance production allow obtaining the target product with a total yield of 61%. Material calculations were carried out to obtain 1 ton of the final diclofenac substance. The numbers of necessary technological equipment are selected, and a basic technological scheme for the production of diclofenac is proposed.

2
6-dichloroaniline
potassium 2-(2-iodophenyl)acetate
copper iodide
diclofenac
basics of technology
material calculations
technological calculations
thermal calculations
basic technological scheme.
  1. Skoutakis, V. A., Carter, C. A., Mickle, T. R., Smith, V. H., Arkin, C. R., Alissandratos, J., &  Petty, D. E. (1988). Review of Diclofenac and evaluation of its place in therapy as a nonsteroidal antiinflammatory agent. Drug Intelligence Clinical Pharmacy, 22(11), 850-859. https://doi.org/10.1177/106002808802201102
  2. Almansa, C., Alfón, J., de Arriba, A. F., Cavalcanti, F. L., Escamilla, I., Gómez, L. A., Miralles, A., Soliva, R., Bartrolí, J., Carceller, E., Merlos, M., & García-Rafanell, J. (2003). Synthesis and structure−activity relationship of a new series of COX-2 selective inhibitors:  1,5-diarylimidazoles. Journal of Medicinal Chemistry, 46(16), 3463-3475. https://doi.org/10.1021/jm030765s
  3. Palkar, M. B., Singhai, A. S., Ronad, P. M., Vishwanathswamy, A. H. M., Boreddy, T. S., Veerapur, V. P., Shaikh, M. S., Rane, R. A., & Karpoormath, R. (2014). Synthesis, pharmacological screening and in silico studies of new class of diclofenac analogues as a promising anti-inflammatory agents. Bioorganic & Medicinal Chemistry, 22(10), 2855-2866. https://doi.org/10.1016/j.bmc.2014.03.043
  4. Dronik, M., Stasevych, M. (2022). Analysis of the pharmaceutical market of diclofenac preparations. Scientific Foundations in Medicine and Pharmacy, 104-123. https://doi.org/10.46299/ISG.2022.MONO.MED.2.4.1
  5. Altman, R., Bosch, B., Brune, K., Patrignani, P.,  Young, C. (2015). Advances in NSAID development: Evolution of Diclofenac products using pharmaceutical technology. Drugs, 75(8), 859-877. https://doi.org/10.1007/s40265-015-0392-z
  6. Diclofenac uses, dosage & side effects. Drugs.com. (n.d.). Retrieved February 13, 2023, from https://www.drugs.com/diclofenac.html
  7. Alsaif, N. A., Bhat, M. A., Al-Omar, M. A., Al-Tuwajiri, H. M., Naglah, A. M.,  Al-Dhfyan, A. (2020). Synthesis of novel diclofenac hydrazones: Molecular docking, anti-inflammatory, analgesic, and ulcerogenic activity. Journal of Chemistry, 2020, 1-12. https://doi.org/10.1155/2020/4916726
  8. Hafeez, F., Zahoor, A. F., Ahmad, S., Ahmad, M., & Faiz, S. (2018). Recent progress in the synthesis of diclofenac based NSAIDs analogs/derivatives. Synthetic Communications, 49(3), 325-350. https://doi.org/10.1080/00397911.2018.1515367
  9. Zhenyu, W., Yongxi, H. U., Lin, G. U. O., Yingjie, R. E. N., Kunpeng, W. A. N. G., & Quan, D. I. N. G. (2019, August 23). CN110156619A Preparation method of diclofenac. https://worldwide.espacenet.com/patent/search/family/067625640/publicati...
  10. kun, Z., & Yanjie, L. (2018). Research progress of synthesis of diclofenac sodium. Topics in Chemical Material Engineering. https://doi.org/10.26480/icnmim.01.2018.276.279
  11. Vardanyan, R. S., & Hruby, V. J. (2006). Synthesis of essential drugs. Elsevier. https://doi.org/10.1016/B978-044452166-8/50036-4
  12. Mei, T.-S., Wang, D.-H., & Yu, J.-Q. (2010). Expedient drug synthesis and diversification via ortho-C−H iodination using recyclable PDI2 as the precatalyst. Organic Letters, 12(14), 3140-3143. https://doi.org/10.1021/ol1010483
  13. CAS SciFinderⁿ - Chemical Compound Database. CAS. (n.d.). Retrieved February 13, 2023, from https://www.cas.org/solutions/cas-scifinder-discovery-platform/cas-scifi...
  14.  Diclofenac. ChemSpider. (n.d.). Retrieved April 4, 2023, from http://www.chemspider.com/Chemical-Structure.2925.html
  15. U.S. National Library of Medicine. (n.d.). Diclofenac. National Center for Biotechnology Information. PubChem Compound Database. Retrieved April 4, 2023, from https://pubchem.ncbi.nlm.nih.gov/compound/Diclofenac#section=Chemical-an...
  16. Sydorov, YU.I., Chuyeshov, V.I., & Novikov, V.P. (2009). Protsesy i aparaty khimiko-farmatsevtychnoyi promyslovosti. Vinnytsya: Nova Knyha.
  17. Stasevych, M.V., Mylyanych, A.O., Strelnykov, L.S., Krutskykh, T.V., Buchkevych, I.R., Zaytsev, O.I., Huzova, I.O., Strilets, O.P., Hladukh, YE.V., & Novikov, V.P. (2018). Tekhnolohichne obladnannya biotekhnolohichnoyi i farmatsevtychnoyi promyslovosti. Lʹviv: Novyy Svit-2000.
  18. Mylyanych, A.O. (2021). Metodychni vkazivky do praktychnykh robit z kursu Ustatkuvannya ta proektuvannya farmatsevtychnykh vyrobnytstv dlya studentiv pershoho (bakalavrsʹkoho) rivnya vyshchoyi osvity spetsialʹnosti226 Farmatsiya, promyslova farmatsiya. Lviv : Vydavnytstvo NU «Lvivska politekhnika».