Kinetic Study of Lornoxicam Hydrolysis

  • sawsan hasan hammodi Department of Pharmaceutical chemistry , College of pharmacy, Hawler Medical University.
  • Dana Muhammad Hamad Ameen Department of Pharmaceutical chemistry , College of pharmacy, Hawler Medical University.
Keywords: lornoxicam; NSAIDs; amide hydrolysis; kinetic study.

Abstract

Gastrointestinal tract (GIT) side effects due to the local action of lornoxicam considered the most common problem that associated with using of this analgesic drug. Masking of the enolic alcohol OH group of lornoxicam to overcoming this problem was the aim, however, applying Williamson ether synthesis led to amide hydrolysis. Therefore, the objective of this study was shifted to study the hydrolytic kinetics and the influence of different bases as a function of time and temperature in the reaction media.

The effects of all bases used in the study on the hydrolysis process of lornoxicam have been studied; NaOH was found to be the strongest followed by Na2CO3 and K2CO3. All three temperatures (25°C, 50°C and 80°C) have approximately similar effect  except  reflux condition that accelerates the hydrolysis process compare with the others. The hydrolysis process is proportional with time.

Williamson ether synthetic procedure that followed to synthesize lornoxicam prodrugs was failed despite attempting different conditions. Using bases were induced the hydrolysis process of lornoxicam. The hydrolysis rate accelerated under reflux more than other conditions. In addition, reaction time gives more hydrolysis process.

References

ARAS NAJMADDIN HAMAD, H. A. M. 2018. Synthesis and spectroscopic study of 1,2-thiazine system incorporating various ester groups. ZANCO Journal of Pure and Applied Sciences, 30, 44-55.
BACCHI, S., PALUMBO, P., SPONTA, A. & COPPOLINO, M. F. 2012. Clinical pharmacology of non-steroidal anti-inflammatory drugs: a review. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Inflammatory and Anti-Allergy Agents), 11, 52-64.
BHAVSAR, K., GAIKWAD, P., BANKAR, V. & PAWAR, S. 2010. Development and validation of uv-spectrophotometric method for simultaneous estimation of paracetamol and lornoxicam in bulk and tablet dosage form.
FRANCO-PÉREZ, M., MOYA-HERNÁNDEZ, R., ROJAS-HERNÁNDEZ, A., GUTIÉRREZ, A. & GÓMEZ-BALDERAS, R. 2011. Tautomeric Ratio and Prototropic Equilibrium Constants of Tenoxicam, a 1H and 13C NMR Theoretical and Experimental Study. The Journal of Physical Chemistry B, 115, 13593-13598.
GOUDA, M. A., HUSSEIN, B. H. & EL-SAID SHERIF, Y. 2017. Synthesis and medicinal importance of oxicams and their analogues. Synthetic Communications, 47, 1709-1736.
HALEN, P. K., MURUMKAR, P. R., GIRIDHAR, R. & YADAV, M. R. 2009. Prodrug designing of NSAIDs. Mini reviews in medicinal chemistry, 9, 124-139.
HALLMANN, S., FINK, M. J. & MITCHELL, B. S. 2015. Williamson ether synthesis: an efficient one-step route for surface modifications of silicon nanoparticles. Journal of Experimental Nanoscience, 10, 588-598.
HOMDRUM, E.-M., LIKAR, R. & NELL, G. 2006. Xefo® rapid: a novel effective tool for pain treatment. European surgery, 38, 342-352.
IVANOVA, D., DENEVA, V., NEDELTCHEVA, D., KAMOUNAH, F. S., GERGOV, G., HANSEN, P. E., KAWAUCHI, S. & ANTONOV, L. 2015. Tautomeric transformations of piroxicam in solution: a combined experimental and theoretical study. Rsc Advances, 5, 31852-31860.
JAYASELLI, J., CHEEMALA, J., GEETHA RANI, D. & PAL, S. 2008. Derivatization of enolic OH of piroxicam: a comparative study on esters and sulfonates. Journal of the Brazilian Chemical Society, 19, 509-515.
JORNADA, D., DOS SANTOS FERNANDES, G., CHIBA, D., DE MELO, T., DOS SANTOS, J. & CHUNG, M. 2015. The prodrug approach: A successful tool for improving drug solubility. Molecules, 21, 42.
KAR, S., DAS, D. & MONDAL, A. 2016. The Analgesic Efficacy of Preoperative Lornoxicam in Prevention of Postoperative Pain after Septoplasty. J Neurol Neurophysiol, 7, 2.
MASSAH, A. R., MOSHARAFIAN, M., MOMENI, A. R., ALIYAN, H., NAGHASH, H. J. & ADIBNEJAD, M. 2007. Solvent‐Free Williamson Synthesis: An Efficient, Simple, and Convenient Method for Chemoselective Etherification of Phenols and Bisphenols. Synthetic communications, 37, 1807-1815.
MODHAVE, D. T., HANDA, T., SHAH, R. P. & SINGH, S. 2011. Stress degradation studies on lornoxicam using LC, LC–MS/TOF and LC–MSn. Journal of pharmaceutical and biomedical analysis, 56, 538-545.
MUHAMAD, S. G., ESMAIL, L. S. & HASAN, S. H. 2016. Kinetic studies of bioethanol production from wheat straw. ZANCO Journal of Pure and Applied Sciences, 28, 97-103.
NAKKA, M., NALLAPATI, S. B., REDDY, L. V., MUKKANTI, K. & PAL, S. 2011. Synthesis, characterization and anti-bacterial screening of Piroxicam based sulfonates. J. Chem. Pharm. Res, 3, 581-8.
PAVIA, D. L., LAMPMAN, G. M., KRIZ, G. S. & VYVYAN, J. A. 2008. Introduction to spectroscopy, Cengage Learning.
RAO, P. & KNAUS, E. E. 2008. Evolution of nonsteroidal anti-inflammatory drugs (NSAIDs): cyclooxygenase (COX) inhibition and beyond. Journal of Pharmacy & Pharmaceutical Sciences, 11, 81-110s.
RAWAL, N., KRØNER, K., SIMIN-GEERTSEN, M., HEJL, C. & LIKAR, R. 2010. Safety of Lornoxicam in the Treatment of Postoperative Pain. Clinical drug investigation, 30, 687-697.
REDASANI, V. K., BHALERAO, O. C., KALASKAR, M. G. & SURANA, S. J. 2017. Synthesis and evaluation of novel mutual prodrugs of Piroxicam. Journal of Pharmaceutical Chemistry, 4, 1-4.
RUSSELL, R. 2001. Non-steroidal anti-inflammatory drugs and gastrointestinal damage—problems and solutions. Postgraduate medical journal, 77, 82-88.
SHAH, D., RANA, J. P., CHHALOTIYA, U. K., BALDANIA, S. & BHATT, K. 2014. Development and validation of a liquid chromatographic method for estimation of dicyclomine hydrochloride, mefenamic acid and paracetamol in tablets. Indian journal of pharmaceutical sciences, 76, 529.
SIDDIQUI, H. L., ZIA-UR-REHMAN, M., ELSEGOOD, M. R. & WEAVER, G. W. 2010. Methyl 2-methyl-4-(oxiran-2-ylmethoxy)-2H-1, 2-benzothiazine-3-carboxylate 1, 1-dioxide. Acta Crystallographica Section E: Structure Reports Online, 66, o333-o333.
SINDHU, A., DEVESWARAN, R., BHARATH, S. & SHARON, F. 2015. Development and Validation of a HPTLC Method for the Estimation of Lornoxicam in Bulk Drug and in Tablet Dosage Form. Pharmaceutical Methods, 6, 109.
XU, S., ROUZER, C. A. & MARNETT, L. J. 2014. Oxicams, a class of nonsteroidal anti‐inflammatory drugs and beyond. IUBMB life, 66, 803-811.
Published
2020-02-25
How to Cite
hammodi, sawsan and Hamad Ameen, D. (2020) “Kinetic Study of Lornoxicam Hydrolysis”, Zanco Journal of Pure and Applied Sciences, 32(1), pp. 65-74. doi: 10.21271/zjpas.32.1.8.
Section
Biology and Medical Researches