JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2020, 69(1):24-32 | DOI: 10.36290/csf.2020.003

Double-coated pellets with semipermeable ethylcellulose coating for detection of cholinesterase inhibitors

Jiří Zeman1, Sylvie Pavloková1, David Vetchý1,*, Vladimír Pitschmann2
1 Department of Pharmaceutics, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic
2 Oritest Ltd., Prague, Czech Republic, Faculty of Biomedical Engineering, Czech Technical University, in Prague, Kladno, Czech Republic

Currently, nerve agents are often used in terrorist attacks or assassinations. In such cases, it is necessary to detect them quickly, accurately and easily right in the field. Detection tubes, which are small devices containing pellets with immobilized cholinesterase and detection reagents, meet these conditions. Their detection mechanism is based on a highly sensitive enzymatic Ellman reaction, when in the absence of cholinesterase inhibitors the pellets develop a visible yellow color, whereas in their presence the carriers retain the original color. The rate of reaction, its sensitivity and the distinct color transition are the key points of the research. In this experiment, double-coated pellets were prepared. The first coating contained the butyrylcholinesterase immobilized in hypromellose, while the second coating consisted of ethylcellulose and triethyl citrate. Based on the properties of such carriers, samples containing lactose dispersed in the ethylcellulose coating were also prepared, which was expected to have an effect on increasing the permeability of the coating and hence the detection rate and color intensity. In addition to selected physicochemical properties, carriers were evaluated for enzyme activity, sensitivity and color transition intensity. Samples showing the best properties were subjected to a 24-months stability test at three different temperatures and humidity.

Keywords: ethylcellulose; pellets; cholinesterase; detection tube; nerve agent
Grants and funding:

This work was supported by ITA FaF/Vetchý/ITA2019 VFU Brno.

Received: September 27, 2019; Accepted: October 19, 2019; Published: January 1, 2020  Show citation

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Zeman J, Pavloková S, Vetchý D, Pitschmann V. Double-coated pellets with semipermeable ethylcellulose coating for detection of cholinesterase inhibitors. Čes. slov. farm. 2020;69(1):24-32. doi: 10.36290/csf.2020.003.
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References

  1. Kaduszkiewicz H., Zimmermann T., Beck-Bornholdt H.-P., van den Bussche H. Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials. BMJ 2005; 331, 321-327. Go to original source... Go to PubMed...
  2. Berrih-Aknin S., Frenkian-Cuvelier M., Eymard B. Diagnostic and clinical classification of autoimmune myasthenia gravis. J. Autoimmun. 2014; 48, 143-148. Go to original source... Go to PubMed...
  3. Pagano G., Rengo G., Pasqualetti G., Femminella G. D., Monzani F., Ferrara N., Tagliati M. Cholinesterase inhibitors for Parkinson's disease: a systematic review and meta-analysis. J. Neurol. Neurosurg. Psychiatry 2015; 86, 767-773. Go to original source... Go to PubMed...
  4. Almasieh M., MacIntyre J. N., Pouliot M., Casanova C., Vaucher E., Kelly M. E. M., di Polo A. Acetylcholinesterase inhibition promotes retinal vasoprotection and increases ocular blood flow in experimental glaucoma. Investig. Opthalmology Vis. Sci. 2013; 54, 3171-3183. Go to original source... Go to PubMed...
  5. Colović M. B., Krstić D. Z., Lazarević-Pašti T. D., Bondžić A. M., Vasić V. M. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr. Neuropharmacol. 2013; 11, 315-335. Go to original source... Go to PubMed...
  6. Teixeira H., Proença P., Alvarenga M., Oliveira M., Marques E. P., Vieira D. N. Pesticide intoxications in the centre of Portugal: three years analysis. Forensic Sci. Int. 2004; 143, 199-204. Go to original source... Go to PubMed...
  7. Chauhan S., Chauhan S., D'Cruz R., Faruqi S., Singh K. K., Varma S., Singh M., Karthik V. Chemical warfare agents. Environ. Toxicol. Pharmacol. 2008; 26, 113-122. Go to original source... Go to PubMed...
  8. Vale J. A., Marrs T. C., Maynard R. L. Novichok: a murderous nerve agent attack in the UK. Clin. Toxicol. 2018; 56, 1093-1097. Go to original source... Go to PubMed...
  9. Petroianu G., Toomes L. M., Petroianu A., Bergler W., Rüfer R. Control of blood pressure, heart rate and haematocrit during high-dose intravenous paraoxon exposure in mini pigs. J. Appl. Toxicol. 1998; 18, 293-298. Go to original source...
  10. Petroianu G. Organophosphate poisoning: the lesser-known face of a toxidrome. Eur. J. Emerg. Med. 2005; 12, 102-103. Go to original source... Go to PubMed...
  11. Balali-Mood M., Balali-Mood K. Neurotoxic disorders of organophosphorus compounds and their managements. Arch. Iran. Med. 2008; 11, 65-89.
  12. Lincová D., Farghali H. Základní a aplikovaná farmakologie. Praha: Galén 2007.
  13. Bajgar J. Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv. Clin. Chem. 2004; 38, 151-216. Go to original source... Go to PubMed...
  14. Zeman J., Vetchý D., Franc A., Pitschmann V. Methods of enzymes immobilization and their use for optical (colorimetric) detection of cholinesterase inhibitors. Chem. Listy 2018; 112, 434-439.
  15. Ellman G. L., Courtney K. D., Andres V., Featherstone R. M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1961; 7, 88-95. Go to original source... Go to PubMed...
  16. Oritest. Oritest Ltd.: http://www.oritest.cz/wp-content/uploads/2017/12/Tubes-CWA-brochure-2012.pdf, cited 26 September, 2019.
  17. Zeman J., Vetchý D., Franc A., Pavloková S., Pitschmann V. Matějovský L. The development of a butyrylcholinesterase porous pellet for innovative detection of cholinesterase inhibitors. Eur. J. Pharm. Sci. 2017; 109, 548-555. Go to original source... Go to PubMed...
  18. Zeman J., Vetchý D., Pavloková S., Franc A., Pitschmann V., Dominik M., Urbanová M., Šeděnková I. Tubes for detection of cholinesterase inhibitors - unique effects of Neusilin on the stability of butyrylcholinesterase-impregnated carriers. Enzyme Microb. Technol. 2019; 128, 26-33. Go to original source... Go to PubMed...
  19. Vysloužil J., Vetchý D., Zeman J., Farsa O., Franc A., Gajdziok J., Vysloužil J., Ficeriová K., Kulich P., Kobliha Z., Pitschmann V. Pellet patented technology for fast and distinct visual detection of cholinesterase inhibitors in liquids. J. Pharm. Biomed. Anal. 2018; 161, 206-213. Go to original source... Go to PubMed...
  20. Vetchý D., Leštinová H., Tušarová I. Methods of pharmaceutical technology in preparation of pellets for detection of acetylcholinesterase inhibitors. Čes. slov. Farm. 2012; 61, 234-239.
  21. Pohanka M., Vlček V., Žďárová-Karasová J., Kuča K., Cabal J. Colorimetric detectors based on acetylcholinesterase and its construction. Vojen. Zdrav. Listy 2010; 79, 9-14.
  22. Pitschmann V., Matějovský L., Vetchý D., Kobliha Z. Enzymatic determination of anticholinesterases using a composite carrier. Anal. Lett. 2016; 49, 2418-2426. Go to original source...
  23. Gelman C, Kramer D. N. US3049411 (A) 1962.
  24. Nisha S., Arun K. S., Gobi N. A review on methods, application and properties of immobilized enzyme. Chem. Sci. Rev. Lett. 2012; 1, 148-155.
  25. Vetchý D., Pitschmann V., Vetchá M., Kašparovský T., Matějovský L. Preparation and evaluation of carriers for detection of cholinesterase inhibitors. Neuroendocrinol. Lett. 2015; 36, 95-99.
  26. Vetchý D., Franc A., Gajdziok J., Vysloužil J., Pitschmann V., Matějovský L. CZ306803 (B6) 2017.
  27. Kato T., Unno K., Goto A. Ethylcellulose microcapsules for selective drug delivery. Methods Enzymol. 1985; 112, 139-150. Go to original source... Go to PubMed...
  28. Siepmann F., Siepmann J., Walther M., MacRae R. J., Bodmeier R. Polymer blends for controlled release coatings. J. Control. Release 2008; 125, 1-15. Go to original source... Go to PubMed...
  29. WHO. Stability testing of active pharmaceutical ingredients and finished pharmaceutical products. WHO Tech. Rep. Ser. 2009; 87-130.
  30. Sienkiewicz G., Pereira R., Rudnic E. M., Lausier J. M., Rhodes C. T. Spheronization of Theophylline-Avicel combinations using a fluidized-bed rotogranulation technique. Drug Dev. Ind. Pharm. 1997; 23, 173-182. Go to original source...
  31. Lecomte F., Siepmann J., Walther M., MacRae R. J., Bod-meier R. Polymer blends used for the aqueous coating of solid dosage forms: importance of the type of plasticizer. J. Control. Release 2004; 99, 1-13. Go to original source... Go to PubMed...
  32. Rekhi G. S., Jambhekar S. S. Ethylcellulose - a polymer review. Drug Dev. Ind. Pharm. 1995; 21, 61-77. Go to original source...
  33. Mokrzycki W. S., Tatol M. Color difference Delta E - a survey. Mach. Graph. Vis. 2011; 20, 383-411.
  34. Perera D. Y. Physical ageing of organic coatings. Prog. Org. Coatings 2003; 47, 61-76. Go to original source...
  35. Heng P. W. S., Chan L. W., Ong K. T. Influence of storage conditions and type of plasticizers on ethylcellulose and acrylate films from aqueous dispersions. J. Pharm. Pharm. Sci. 2003; 7 (6), 334-344.
  36. Rabišková M. Technological parameters of drug microforms, their importance and methods of their determination. Čes. slov. Farm. 1996; 45, 177-179.
  37. Deasy P. B, Law M. F. L. Use of extrusion-spheronization to develop an improved oral dosage form of indomethacin. Int. J. Pharm. 1997; 148, 201-209. Go to original source...




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