Substantiation of an approach to determination of ketoprofen macrogol 400 esters

Authors

DOI:

https://doi.org/10.15587/2519-4852.2021.235980

Keywords:

ketoprofen, macrogol 400, ester, impurity, chromatogram, absorption spectrum, molecular mass

Abstract

The aim. The work is concerned with the substantiation of the approach to the identification and quantitative determination of ketoprofen macrogol 400 esters.

Materials and methods. Ketoprofen, macrogol 400, ketoprofen macrogol 400 ester (KM400E), as well as model cream-gels were studied by the following methods: absorption spectrophotometry ultraviolet (UV) and visible, high-performance liquid chromatography (HPLC), gas chromatography (GC), GC / mass spectrometry, nuclear magnetic resonance (NMR) spectrometry and thermogravimetry.

Results. It was found by GC and GC / mass spectrometry that the average molecular mass (Mr) of the test macrogol 400 is 383.50 and it contains oligomers with molecular masses from 150.17 to 546.65. KM400E, which is a mixture of esters of ketoprofen with macrogol oligomers, was synthesized. The formed esters were characterized by 1H NMR spectra. It was shown that the ratio of the average molecular mass of KM400E, calculated for monoesters, and the molecular mass of ketoprofen corresponds to the ratio of specific absorbances of solutions of ketoprofen and solutions of KM400E, this fact indicated the formation of monoesters. Taking into account the risk of variability of the fractional composition of macrogol 400 in different batches, it is advisable to quantify KM400E using ketoprofen reference standard (RS) and not KM400E RS. Using HPLC with diode array detection the peak of KM400E should be identified by the UV absorption spectrum with λmax≈255 nm, which is characteristic for ketoprofen, and the relative retention time (RRt) of the peak; KM400E should be quantified by the content of ketoprofen in this impurity.

During storage of model cream-gels the content of KM400E impurity is significantly lower than the content of ketoprofen propylene glycol ester (mixture of isomers).

Conclusions. The approach to the identification and quantitative determination of KM400E is substantiated. The analytical procedure for determination of KM400E impurity by HPLC with a diode array detection using ketoprofen RS was developed. Correctness of the procedure was proved by the results of the validation studies.

Author Biographies

Elena Bezuglaya, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

PhD, Senior Researcher, Head of Laboratory.

Laboratory of Technology and Analysis of Medicinal Products

Igor Zinchenko, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

PhD, Junior Researcher

Laboratory of Technology and Analysis of Medicinal Products

Nikolay Lyapunov, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

Doctor of Pharmaceutical Sciences, Professor, Leading Researcher

Laboratory of Technology and Analysis of Medicinal Products

Hanna Vlasenko, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

PhD, Junior Researcher

Department of Luminescent Materials and Dyes

Vladimir Musatov, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

PhD, Senior Researcher

Department of Organic and Bioorganic Chemistry

References

  1. Derry, S., Wiffen, P. J., Kalso, E. A., Bell, R. F., Aldington, D., Phillips, T. et. al. (2017). Topical analgesics for acute and chronic pain in adults – an overview of Cochrane Reviews. Cochrane Database of Systematic Reviews, 5. doi: http://doi.org/10.1002/14651858.cd008609.pub2
  2. Zeng, C., Wei, J., Persson, M. S. M., Sarmanova, A., Doherty, M., Xie, D. et. al. (2018). Relative efficacy and safety of topical non-steroidal anti-inflammatory drugs for osteoarthritis: a systematic review and network meta-analysis of randomised controlled trials and observational studies. British Journal of Sports Medicine, 52 (10), 642–650. doi: http://doi.org/10.1136/bjsports-2017-098043
  3. Rother, M., Conaghan, P. G. (2013). A Randomized, Double-blind, Phase III Trial in Moderate Osteoarthritis Knee Pain Comparing Topical Ketoprofen Gel with Ketoprofen-free Gel. The Journal of Rheumatology, 40 (10), 1742–1748. doi: http://doi.org/10.3899/jrheum.130192
  4. Sarzi-Puttini, P., Atzeni, F., Lanata, L., Bagnasco, M. (2013). Efficacy of ketoprofen vs. ibuprofen and diclofenac: a systematic review of the literature and meta-analysis. Clinical and Experimental Rheumatology, 31 (5), 731–738.
  5. Davishnia, N. V. (2016). Eksperymentalne obgruntuvannia kombinovanoho zastosuvannia hliukozaminu z ketoprofenom u formi krem-heliu pry osteoartryti. Kharkiv, 20.
  6. Lyapunov, N. A., Zinchenko, I. A., Bezuglaya, E. P., Lysokobilka, A. A. (2019). Effect of the Ketoprofen Distribution in Cream-gels on the Formation of the Impurities. Drug Development & Registration, 8 (2), 55–64. doi: http://doi.org/10.33380/2305-2066-2019-8-2-55-64
  7. Buckingham, R. (Ed.) (2020). Martindale: The Complete Drug Reference. London: Pharmaceutical Press, 4912.
  8. Patil, S. J., Shirote, P. J. (2012). Synthesis and evaluation of carrier linked prodrug of ketoprofen with glucosamine. Journal of Pharmacy Research, 5, 954–957. Available at: http://jprsolutions.info/files/final-file-57de8ca6e160e8.65433122.pdf
  9. The European Pharmacopoeia (2019). European Directorate for the Quality of Medicines & HealthCare of the Council of Europe. Strasbourg, 5224.
  10. British Pharmacopoeia (2020). London: The Stationery Office. Available at: https://www.pharmacopoeia.com/
  11. The United States Pharmacopoeia, 41 – NF 36 (2018). The United States Pharmacopoeial Convention. Rockville. Available at: https://www.worldcat.org/title/united-states-pharmacopeia-2018-usp-41-the-national-formulary-nf-36/oclc/1013752699
  12. Derzhavna Farmakopeia Ukrainy. Vol. 1 (2015). Kharkiv: Derzhavne pidpryiemstvo «Ukrainskyi naukovyi farmakopeinyi tsentr yakosti likarskykh zasobiv», 1128.
  13. Dhokchawle, B., Tauro, S., Bhandari, A. (2015). Ester Prodrugs of Ketoprofen: Synthesis, Hydrolysis Kinetics and Pharmacological Evaluation. Drug Research, 66 (1), 46–50. doi: http://doi.org/10.1055/s-0035-1548908
  14. Redasani, V. K., Bari, S. B. (2012). Synthesis and evaluation of mutual prodrugs of ibuprofen with menthol, thymol and eugenol. European Journal of Medicinal Chemistry, 56, 134–138. doi: http://doi.org/10.1016/j.ejmech.2012.08.030
  15. Chawla, G., Ranjan, C., Kumar, J., A. Siddiqui, A. (2017). Chemical Modifications of Ketoprofen (NSAID) in Search of Better Lead Compounds: A Review of Literature From 2004-2016. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 15 (3), 154–177. doi: http://doi.org/10.2174/1871523016666170217094722
  16. Choi, H.-K., Chun, M.-K., Lee, S. H., Jang, M. H., Kim, H. D., Jung, C. S., Oh, S. Y. (2007). In vitro and in vivo study of poly(ethylene glycol) conjugated ketoprofen to extend the duration of action. International Journal of Pharmaceutics, 341 (1-2), 50–57. doi: http://doi.org/10.1016/j.ijpharm.2007.03.045
  17. Note for Guidance on Impurities in New Drug Products (2006). СРМР/ICH/2738/99 (ICH Topic Q3В (R2)). Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-3-b-r2-impurities-new-drug-products-step-5_en.pdf
  18. Muro, S. (Ed.) (2016). Drug Delivery Across Physiological Barriers. Pan Stanford Reference, 426. doi: http://doi.org/10.1201/b19907
  19. Alkilani, A., McCrudden, M. T., Donnelly, R. (2015). Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the Stratum Corneum. Pharmaceutics, 7 (4), 438–470. doi: http://doi.org/10.3390/pharmaceutics7040438
  20. Bezuglaya, E. P., Zinchenko, I. A., Lyapunov, N. A., Stolper, Yu. M. (2019). Pat. No. 2685436 C1 RU. Transdermalniy preparat dlya lecheniya i profilaktiki bolezney sustavov i myagkikh tkaney. MPK: A61K 31/7008, A61K 31/192, A61K 31/351, A61K 47/10, A61P 19/02. declareted: 22.06.2018; published: 18.04.2019, No. 11.
  21. Zinchenko, I. A., Lyapunov, N. A., Bezuglaya, E. P. (2017). Study of the formation of ketoprofen impurities in model solutions. Farmakom, 4, 16–22.
  22. Sheskey, P. J., Hancock, B. C., Moss, G. P., Goldfarb, D. J. (Ed.) (2020). Handbook of Pharmaceutical Excipients, Ninth edition. London: Pharm. Press, 1296.
  23. Lyapunov, A. N. (2015). Solubility study of meloxicam and meloxicam trometamol in some non-aqueous solvents and mixed solvents. Farmakom, 2, 41–48.
  24. Note for Guidance on Pharmaceutical Development, Part I (2009). EMEA/CHMP/167068/2004 (ICH Topic Q 8 (R2) Pharmaceutical Development).
  25. LGC standards. Available at: https://www.lgcstandards.com
  26. TLC standards. Available at: https://www.tlcstandards.com
  27. Onigbinde, A., Nicol, G., Munson, B. (2001). Gas Chromatography/Mass Spectrometry of Polyethylene Glycol Oligomers. European Journal of Mass Spectrometry, 7 (3), 279–291. doi: http://doi.org/10.1255/ejms.438
  28. Lyapunov, N. A., Zinchenko, I. A., Bezuglaya, E. P. (2018). Identification and assay of the ketoprofen esters. Belgorod State University Scientific Bulletin Medicine Pharmacy, 41 (3), 473–483. doi: http://doi.org/10.18413/2075-4728-2018-41-3-473-483
  29. Note for Guidance on Validation of Analytical Procedures: Text and Methodology, Step 5 (1995). CPMP/ICH/381/95 (ICH Topic Q 2 (R1) Validation of Analytical Procedures: Text and Methodology).

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Published

2021-06-30

How to Cite

Bezuglaya, E., Zinchenko, I., Lyapunov, N., Vlasenko, H., & Musatov, V. (2021). Substantiation of an approach to determination of ketoprofen macrogol 400 esters. ScienceRise: Pharmaceutical Science, (3(31), 51–63. https://doi.org/10.15587/2519-4852.2021.235980

Issue

No. 3(31) (2021)

Section

Pharmaceutical Science

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Copyright (c) 2021 Elena Bezuglaya, Igor Zinchenko, Nikolay Lyapunov, Hanna Vlasenko, Vladimir Musatov

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