Editor-in-Chief : V.K. Rastogi
|Asian Journal of Physics||Vol. 31 No 2, 2022, 355-364|
Drug-drug interaction: the case of flubendazole and doxycycline hyclate investigated by Raman spectroscopy
Ilirjana Bajama, Luisa Andronie, Simona Cinta Pinzaru
This paper expands the applicability of Raman spectroscopy in veterinary field, aiming to search for spectroscopic signature of the drug-drug interaction between Rombendazole and Doxycycline hyclate, commercially available for veterinary use and prescribed in poultry with simultaneous nematodes and respiratory infections. The failure of treatment in chickens with symptoms of respiratory infections and parasitic worms, who were given the combination of Rombendazole and doxycycline hyclate triggered and motivated this study, to (1) identify the active ingredients in commercially formulated Rombendazole tablets; and (2) to investigate the Raman spectroscopy signature of the mixed, kneading product of the two drugs in solid phase, consistent with the simultaneous administration, in search for their direct molecular interaction as a possible cause of vet treatment failure. Raman spectroscopy enabled the identification of flubendazole as the genuine active ingredient of commercial Rombendazole and found changes in Raman signature of the active ingredient in spectra of solid mixtures, due to the possible interaction of flubendazole through the N atom from benzimidazole ring with the doxycycline. The high degree of overlap between the Raman spectra of the two compounds raised additional difficulties along with the co-existence of excipients, however, spectral evidence of interaction between the two solid drugs are reported. © Anita Publications. All rights reserved.
Keywords: Rombendazole, Doxycycline hyclate, Veterinary drugs, Raman Spectroscopy,
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Method: Single- anonymous; Screened for Plagiarism? Yes
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- Tondepu C, Toth R, Navin C V, Lawson L S, Rodriguez J D, Screening of unapproved drugs using portable Raman spectroscopy, Anal Chim Acta, 973(2017)75–81.
- Kiss K, Vass P, Farkas A, Hirsch E, Szabó E, Mező G, Nagy ZK, Marosi A, A solid doxycycline HP-β-CD formulation for reconstitution (iv bolus) prepared by scaled-up electrospinning, J Pharmaceutics, 586(2020)119539; doi.org/10.1016/j.ijpharm.2020.119539.
- de Araujo G L B, Ferreira F F, Bernardes C E S, Sato J A P, Gil O M, de Faria D L A, Loebenberg R, Byrn S R, Ghisleni D D M, Bou-Chacra N A, Pinto T J A, Antonio S G, Ferraz H G, Zemlyanov D, Gonçalves D S, da Piedade M E M, A New Thermodynamically Favored Flubendazole/Maleic Acid Binary Crystal Form: Structure, Energetics, and in Silico PBPK Model-Based Investigation, Crystal Growth Des, 18(2018)2377–2386.
- Mansour A M, Bakry E M E, Abdel-Ghani N T, Flubendazole Pd (II) complexes: structural studies, cytotoxicity, and quantum chemical calculations, J Iran Chem Soc, 13(2016)1429–1437.
- John Wiley & Sons, Inc. SpectraBase; SpectraBase Compound ID=1t48QnTSUk SpectraBase Spectrum ID=IspwaTQq3c4; https://spectrabase.com/spectrum/IspwaTQq3c4 (accessed 12/15/2021).
- https://www.drugs.com/international/flubendazole.html (accessed 12/15/2021)
- Mackenzie C, A report submitted to Dr Gary Weil (PI DOLF), Mi 48824, https://cpb-us-w2.wpmucdn.com/sites.wustl.edu/dist/3/1548/files/2014/12/A-review-of-flubendazole-Report.pdf, (accessed 12/15/2021).
- Sungpradit S, Sanprasert V, Chapter 4 in Molecular Advancements in Tropical Diseases Drug Discovery, Misra G, Srivastava V (eds), (Academic Press), 2020, pp 6–94.
- Bogardus J B, Blackwood R K, Solubility of doxycycline in aqueous solution, J Pharma Sci, 68(1979)188–194.
- https://ec.europa.eu/health/documents/community-register/2010/2010061476837/anx_76837_ro.pdf (accessed 12/15.2021).
- Veij M D, Vandenabeele P, Beer T D, Remon J P, Moens L, Reference database of Raman spectra of pharmaceutical excipients, J Raman Spectrosc, 40(2009)297–307.
- Lakio S, Vajna B, Farkas I, Salokangas H, Marosi G, Yliruusi J Challenges in detecting magnesium stearate distribution in tablets, AAPS PharmSciTech, 14(2013)435–444.
- Zeng Z, Tan X, Liu Y, Tian S, Zeng G, Jiang L, Liu S, Liu N, Yin Z, Frontiers in chemistry, 6(2018)8; doi.org/10.3389/fchem.2018.00080, e-collection 2018.
- Ivashchenko O, Jurga-Stop J, Coy E, Peplinska B, Pietralik Z, Jurga S, Fourier transform infrared and Raman spectroscopy studies on magnetite/Ag/antibiotic nanocomposites, Appl Surf Sci, 364(2016)400-409.
- Leypold C F, Reiher M, Brehm B, Schmitt M O, Schneider S, Matousek P, Towrie M Tetracycline and derivatives—assignment of IR and Raman spectravia DFT calculations, Phys Chem Chem Phys, 5 (2003)1149–1157.
- John Wiley & Sons, Inc. SpectraBase; SpectraBase Compound ID=1t48QnTSUk SpectraBase Spectrum ID=2VQclY24RC9, https://spectrabase.com/spectrum/2VQclY24RC9 (accessed 10/29/2021).
- Socrates G, Infrared and Raman Characteristic Group Frequencies: Tables and Charts, 3rd Edn, 2002, https://www.wiley.com/en-us/ red+and+Raman+Characteristic+Group+Frequencies%3A+Tables+and+ Charts%2C+3rd+Edition-p-9780470093078] (accessed 12/15.2021).
- Mohan S, Sundaraganesan N, Mink J, FTIR and Raman studies on benzimidazole, Spectrochim Acta, A47(1991)1111–1115.
- Vialpando M, Smulders S, Bone S, Jager C, Vodak D, Van Speybroeck M, Verheyen L, Backx K, Boeykens P, Brewster M E, Ceulemans J, Novoa de Armas H, Van Geel K, Kesselaers E, Hillewaer V, Lachau-Durand S, Meurs G, Psathas P, Van Hove B, Verreck G, Mackie C, Evaluation of three amorphous drug delivery technologies to improve the oral absorption of flubendazole, J Pharma Sci, 105(2016)2782–2793.