Research Articles

Synthesis and evaluation of novel mutual prodrugs of Piroxicam

Vol. 4 No. 1 (2017) 1-4 Published January 31, 2017

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Abstract

Therapeutic efficacy of piroxicam can be improved by retarding gastrointestinal side effects by means of temporarily modification of enolic hydroxyl group chemically. The NSAIDs such as aceclofenac, ibuprofen, mefenamic acid and naproxen were selected as promoities with the aim of getting synergistic effect through these well known pharmaco-counter parts. The targeted prodrugs are synthesized successfully and confirmed by characterization. Synthesis involved chlorination of NSAIDs and coupling of this acid chloride with piroxicam through enolic hydroxyl group to get ester derivatives. Mutual prodrugs were evaluated by hydrolysis study at different pH (acidic, neutral, alkaline) using phosphate buffer. Prodrug derivatives were found to be stable at acidic and neutral pH but prone to hydrolysis at alkaline pH. Thus the objective of the presented study was to overcome the undesirable side effects of NSAIDs. Thus, current studies confirms that the mutual prodrug approach can be applied  effectively in order to  achieve the purpose of raising effectiveness of piroxicam under two lines; firstly, masking of enolic hydroxyl group through acids and converting them to esters and secondly, utilizing the known NSAIDs for achieving the synergistic effect.

References

  1. Blower, A.; Armstrong, C. Perforated duodenal ulcers. Br J Sur 1987, 74 (8), 759-759.
  2. https://doi.org/10.1002/bjs.1800740843 DOI: https://doi.org/10.1002/bjs.1800740843
  4. Pal, S.; Bindu, P.; Dubey, P. K.; Chakraborty, S.; Mukherjee, A. K. Synthesis and structure analysis of cyclodehydration product of piroxicam: A metabolite detected in dogs and monkeys. Eur J Med Chem 2009, 44 (8), 3368-3371.
  5. https://doi.org/10.1016/j.ejmech.2009.03.010 DOI: https://doi.org/10.1016/j.ejmech.2009.03.010
  7. Kawai, S.; Kojima, F.; Kusunoki, N. Recent advances in nonsteroidal anti-inflammatory drugs. Allergol Int 2005, 54 (2), 209-215.
  8. https://doi.org/10.2332/allergolint.54.209 DOI: https://doi.org/10.2332/allergolint.54.209
  10. Kean, W. F.; Buchanan, W. W. The use of NSAIDs in rheumatic disorders 2005: a global perspective. Inflammopharmacol 2005, 13 (4), 343-370.
  11. https://doi.org/10.1163/156856005774415565 DOI: https://doi.org/10.1163/156856005774415565
  13. Bhosle, D.; Bharambe, S.; Gairola, N.; Dhaneshwar, S. S. Mutual Prodrug Concept: F Mutual Prodrug Concept: Fundamentals and undamentals and Applications. Indian J Pharm Sci 2006, 286.
  15. Jayaselli, J.; Cheemala, J.; Geetha Rani, D. P.; Pal, S. Derivatization of enolic OH of piroxicam: a comparative study on esters and sulfonates. J Braz Chem Soc 2008, 19 (3), 509-515.
  16. https://doi.org/10.1590/S0103-50532008000300019 DOI: https://doi.org/10.1590/S0103-50532008000300019
  18. Redasani, V. K.; Shinde, A. B.; Surana, S. J. Anti-inflammatory and gastroprotective evaluation of prodrugs of piroxicam. Ulcers 2014, 2014, Article ID 729754. DOI: https://doi.org/10.1155/2014/729754
  20. Carty, T. J.; Marfat, A.; Moore, P. F.; Falkner, F. C.; Twomey, T. M.; Weissman, A. Ampiroxicam, an anti-inflammatory agent which is a prodrug of piroxicam. Inflammation Res 1993, 39 (3), 157-165.
  21. https://doi.org/10.1007/bf01998969 DOI: https://doi.org/10.1007/BF01998969
  23. Mahfouz, N. M.; Omar, F. A.; Aboul-Fadl, T. Cyclic amide derivatives as potential prodrugs II: N-hydroxymethylsuccinimide-/isatin esters of some NSAIDs as prodrugs with an improved therapeutic index. Eur J Med Chem 1999, 34 (7), 551-562.
  24. https://doi.org/10.1016/S0223-5234(00)80025-2 DOI: https://doi.org/10.1016/S0223-5234(00)80025-2
  25. https://doi.org/10.1016/S0223-5234(99)00236-6 DOI: https://doi.org/10.1016/S0223-5234(99)00236-6
  27. Redasani, V. K.; Bari, S. B. Synthesis and evaluation of mutual prodrugs of ibuprofen with menthol, thymol and eugenol. Eur J Med Chem 2012, 56, 134-138.
  28. https://doi.org/10.1016/j.ejmech.2012.08.030 DOI: https://doi.org/10.1016/j.ejmech.2012.08.030
  30. Omar, F. A. Cyclic amide derivatives as potential prodrugs. Synthesis and evaluation of N-hydroxymethylphthalimide esters of some non-steroidal anti-inflammatory carboxylic acid drugs. Eur J Med Chem 1998, 33 (2), 123-131.
  31. https://doi.org/10.1016/S0223-5234(98)80037-8 DOI: https://doi.org/10.1016/S0223-5234(98)80037-8
  33. Redasani, V. K.; Bari, S. B., Synthesis and evaluation of glyceride prodrugs of naproxen. Open J. Med. Chem. 2013, 3, 87-92.
  34. https://doi.org/10.4236/ojmc.2013.33011 DOI: https://doi.org/10.4236/ojmc.2013.33011

Author information

  • Vivekkumar K Redasani

    R. C. Patel Institute of Pharmaceutical Education and Research

  • Omkar C. Bhalerao

    R. C. Patel Institute of Pharmaceutical Education and Research

  • Mohan G. Kalaskar

    R. C. Patel Institute of Pharmaceutical Education and Research

  • Sanjay J. Surana

    R. C. Patel Institute of Pharmaceutical Education and Research

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Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

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Redasani, V. K.; Bhalerao, O. C.; Kalaskar, M. G.; Surana, S. J. Synthesis and Evaluation of Novel Mutual Prodrugs of Piroxicam. J Pharm Chem 2017, 4 (1), 1-4. https://doi.org/10.14805/jphchem.2017.art69.
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Received
September 15, 2016
Published
January 31, 2017
Section
Research Articles
Pages
1-4

Keywords

  • Mutual prodrugs
  • piroxicam
  • NSAIDs
  • esters
  • hydrolysis

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