DEVELOPMENT AND PHARMACOKINETIC STUDY OF THE ORIGINAL DOSAGE FORM  GLICLAZIDE SUSPENSION

DOI: https://doi.org/10.29296/25877313-2020-12-05
Issue: 
12
Year: 
2020

S.E. Storozhenko Senior Lecturer, Department of Pharmaceutical Technology and Pharmacognosy with Postgraduate Education Course, Krasnoyarsk State Medical University named after Professor V.F. Voino-Yasenetsky (Krasnoyarsk) E-mail: panisher-13@mail.ru V.A. Kutyakov Ph.D. (Biol.), Associate Professor, Department of Biological Chemistry with a Course in Medical, Pharmaceutical and Toxicological Chemistry, Krasnoyarsk State Medical University named after Professor V.F. Voino-Yasenetsky; Forensic Chemist KGBUZ «Krasnoyarsk Regional Bureau of Forensic Medicine» (Krasnoyarsk) E-mail: victor-koutjakov@yandex.ru E.F. Stepanova Dr.Sc. (Pharm.), Professor, Department of Pharmaceutical Technology with a Course in Medical Biotechnology, Pyatigorsk Medical and Pharmaceutical Institute - branch of the Volgograd State Medical University (Pyatigorsk) E-mail: efstepanova@mail.ru O.F. Veselova Ph.D. (Med.), Head of the Department of Pharmacology and Pharmaceutical Consulting with a Course of Postgraduate Education, Krasnoyarsk State Medical University named after Professor V.F. Voino-Yasenetsky (Krasnoyarsk) E-mail: veselovaof@mail.ru

Relevance: one of the most common forms of diabetes mellitus (DM) is type 2 diabetes mellitus. A personalized approach to diabetes therapy pre-supposes adequate glycemic control and the availability of original drugs with various pharmacokinetic parameters, incl. bioavailability. One of these dosage forms is a suspension that meets a number of good manufacturing practice (GMP) requirements and has several advantages over other dos-age forms. Purpose of the work: to study the bioavailability of Gliclazidum from a suspension in comparison with a tablet dosage form. Material and methods: the study of the bioavailability of Gliclazidum from the suspension and tablets was carried out on male Vistar rats weighing 190-200 grams. The animals were injected with the developed suspension of Gliclazidum and the reference drug - tablets "Diabeton MV" ("ServierRus", Russia, active ingredient - Gliclazidum). Form of administration of drugs - intragastrically at the rate of 60 mg / kg of body weight of animals. Blood sampling was carried out at intervals from 2 to 24 hours after drug administration. Extraction of Gliclazidum from blood plasma was carried out with dichloromethane at a pH of 9.5, the extract was dried, dissolved in 100 μl of methanol, and the solution was analyzed by liquid chromatography. The Gliclazidum content was calculated using the internal standard method. A calibration graph was preliminarily constructed, where a "blank" (not contain-ing gliclazide and anecaine - internal standard) blood plasma was used. The study was carried out on a liquid microcolumn chromatograph "Milichrom - A02" with a UV spectrophotometric detector. Results: it was found that the concentration of Gliclazidum after 2, 4 hours, as well as its residual concentration in the blood plasma of rats 12 and 24 hours after administration of the suspension is higher than after administration of tablets. The data obtained indicate a higher bioavailability of the drug from the suspension compared to the tableted dosage form. Conclusions: a higher bioavailability of Gliclazidum from a suspension than from tablets has been experimentally established, which confirms the feasibility of its medical use.

Keywords: 
suspension of gliclazide
pharmacokinetics of gliclazide
determination of gliclazide in blood plasma

References: 
  1. Dedov I.I., Shestakova M.V., Vikulova O.K., Zheleznjakova A.V., Isakov M.A. Caharnyj diabet v rossijskoj federacii: rasprostranennost', zabolevaemost', smertnost', parametry uglevodnogo obmena i struktura saharosnizhajushhej terapii po dannym federal'nogo registra saharnogo diabeta, status 2017 g. Saharnyj diabet. 2018; 3: 144–159.
  2. Shestakova M.V., Suhareva O.Ju. Diagnostika i vybor metoda lechenija saharnogo diabeta 2 tipa. Klinicheskaja farmakologija i terapija. 2018; 27(2): 3–9.
  3. Feng W., Gao C., Bi Y., et al. Randomized trial comparing the effects of gliclazide, liraglutide, and metform in on diabetes withnon-alcoholic fatty liver disease. J. Diabetes. 2017; 9(8):800–809.
  4. Singh A.K., Singh R. Is gliclazide a sulfonylurea with difference? A review in 2016. Expert Rev. Clin. Pharmacol. 2016; 9(6): 839–851.
  5. Demidova T.Ju. Proizvodnye sul'fonilmocheviny v svete dokazatel'noj mediciny i algoritmov upravlenija saharnym diabetom 2 tipa. Terapija. 2016; 4(8):
  6. 65–74.
  7. Pavec N.R., Dzhavahjan M.A. Analiz nomenklatury lekarstvennyh preparatov, primenjaemyh pri saharnom diabete. Voprosy biologicheskoj, medicinskoj i farmacevticheskoj himii. 2020; 23 (6): 10–15.
  8. Pantjuhin A.V., Petrov A.Ju., Pantjuhina E.V. Metodologicheskie jetapy razrabotki farmacevticheskih suspenzij. Fundamental'nye issledovanija. 2012; 4:
  9. 415–419.
  10. Storozhenko S.E., Stepanova Je.F., Larionova I.A., Potkina N.A., Malahova L.V. Razrabotka innovacionnyh lekarstvennyh form dlja lechenija saharnogo diabeta: preparaty gliklazida, mikrobiologicheskie issledovanija. Sovremennye problemy nauki i obrazovanija. 2019; 4: 55–63.
  11. Storozhenko S.E., Stepanova Je.F., Veselova O.F., Slivkin A.I., Morozov A.V., Savel'eva E.E. Innovacionnye lekarstvennye formy gliklazida – suspenzija i transdermal'nyj plastyr': opredelenie saharosnizhajushhej aktivnosti. Vestnik VGU. Serija: himija. biologija. Farmacija. 2020; 1: 105–110.
  12. Belolipeckaja V.G., Suhanov Ja.V. Farmakokineticheskie issledovanija i prakticheskaja medicin. Racional'naja farmakoterapija v kardiologii. 2005; 2: 43–47.