Phleboprotectors based on flavonoids: dosage forms, biopharmaceutical characteristics, technological features
- Authors: Stepanova E.F.1, Remezova I.P.1, Shevchenko A.M.1, Morozov A.V.1, Maltseva V.K.1
-
Affiliations:
- Pyatigorsk Medical and Pharmaceutical Institute - a branch of the Volgograd State Medical University
- Issue: Vol 8, No 6 (2020)
- Pages: 405-415
- Section: Articles
- URL: https://journals.rcsi.science/2307-9266/article/view/111659
- DOI: https://doi.org/10.19163/2307-9266-2020-8-6-405-415
- ID: 111659
Cite item
Abstract
Micronized purified flavonoid fraction (MPFF) is the original phlebotropic drug. Its marketed form (Detralex®) consists of 90% diosmin and 10% of other flavonoids. Calculated as hesperidin, it is the most widely used drug today. Diosmin and hesperidin, which are parts of the majority of venoactive drugs, are sparingly water-soluble compounds, and this feature can effect on their clinical efficacy. One of the ways to increase the solubility of these compounds leading to an increase in bioavailability, is the micronization of the active ingredients.
The aim of the investigation is a comparative determination of the dynamics and dissolution efficiency of the drugs containing bioflavonoid fractions in the dissolution test, as well as the analysis of the micronization degree and its impact on technology and biopharmaceutical parameters.
Materials and methods. A biopharmaceutical release profile was determined using HPLC. Disintegration, characteristics of the shape and size of the tablets’ particles were determined according to the methods of the State Pharmacopoeia of the XIV edition.
Results. The objects created with the use of diosmin and hesperidin, have been considered in detail. The role of technological solutions in relation to the corresponding dosage forms is notified. Detailed biopharmaceutical characteristics have been established with a choice of HPLC-based release control methodology. All the drugs in this group have a low water solubility leading to the maximum bioavailability for Detralex® which is about 1.26%; and no more than 0.2% for other analyzed models.
Conclusion. Detralex® dominates among the analyzed objects (tablets) in terms of the release rate. With regard to the overall quantitative indicators of release, the actual numbers are quite low, which is associated with the poor water solubility of the active substances.
Keywords
Full Text
##article.viewOnOriginalSite##About the authors
Eleonora F. Stepanova
Pyatigorsk Medical and Pharmaceutical Institute - a branch of the Volgograd State Medical University
Author for correspondence.
Email: efstepanova@yandex.ru
ORCID iD: 0000-0002-4082-3330
Doctor of Sciences (Pharmacy), Professor of the Department of pharmaceutical technology with a course in medical biotechnology
Russian Federation, 11, Kalinin Ave., Pyatigorsk, Russia, 357532Irina P. Remezova
Pyatigorsk Medical and Pharmaceutical Institute - a branch of the Volgograd State Medical University
Email: i.p.remezova@pmedpharm.ru
ORCID iD: 0000-0003-3456-8553
Doctor of Sciences (Pharmacy), Associate Professor of the Department of toxicological and analytical chemistry
Russian Federation, 11, Kalinin Ave., Pyatigorsk, Russia, 357532Alexander M. Shevchenko
Pyatigorsk Medical and Pharmaceutical Institute - a branch of the Volgograd State Medical University
Email: nplfarmak-50@yandex.ua
ORCID iD: 0000-0001-8373-5907
Doctor of Sciences (Pharmacy), Associate Professor, Professor of the Department of pharmaceutical technology with a course in medical biotechnology
Russian Federation, 11, Kalinin Ave., Pyatigorsk, Russia, 357532Andrey V. Morozov
Pyatigorsk Medical and Pharmaceutical Institute - a branch of the Volgograd State Medical University
Email: andrewmorozov@mail.ru
ORCID iD: 0000-0002-8553-4073
Doctor of Sciences (Pharmacy), Associate Professor of the Department of pharmaceutical chemistry
Russian Federation, 11, Kalinin Ave., Pyatigorsk, Russia, 357532Victoria K. Maltseva
Pyatigorsk Medical and Pharmaceutical Institute - a branch of the Volgograd State Medical University
Email: maltsev.tom@mail.ru
ORCID iD: 0000-0001-5886-6219
postgraduate student of the 4th year of study at the Department of pharmaceutical technology with a course in medical biotechnology
Russian Federation, 11, Kalinin Ave., Pyatigorsk, Russia, 357532References
- Bogachev VYu, Golovanova OE, Kuznetsov AN, Shekoyan AO. Bioflavonoids and their importance in angiology. Focus on diosmin. Angiology and vascular surgery. 2013;19(1):1–9. Russian
- Savelyev VS, Pokrovsky AV, Sapelkin SV, Bogachev VYu, Bogdanets LI, Zolotukhin IA. Micronized diosmin (Detralex®) in the treatment of trophic ulcers of venous etiology – European experience. Angiology and vascular surgery. 2006;12(3):53–60. Russian
- Zhukembaeva AM. Chronic venous insufficiency in varicose veins of the lower extremities: pathogenesis, treatment. Bulletin of the Kyrgyz-Russian Slavic University. 2015; 15(11):61–-64. Russian
- Shaidakov EV, Tsarev OI, Bulatov VL, Grigoryan AG, Rosukhovsky DA. Efficacy and tolerability of Dioflan and Detralex in the treatment of chronic venous diseases: an open comparative international multicenter randomized prospective study. Evidence-based medicine and pharmacoeconomics. 2015;6(18):95–115. Russian
- Bogachev VYu, Golovanova OV, Kuznetsov AN, Shekoyan LO. Advisability of perioperative phleboprotection in endovascular treatment of lower in varicose disease: first initial results of the decision study. Angiology and vascular surgery. 2012;18(2):90–95. Russian
- Bogachev VYu, Boldin BV, Turkin PYu. Detralex-phlebosclerosing treatment. Results of the national multicenter follow up programme vein act prolonged-c1. Angiology and vascular surgery. 2018;24(1):102–106. Russian
- Shneur SYa, Bahno DA, Dzhumanova D. Analiz potrebitel’skih predpochtenij venotoniziruyushchih sredstv. Tverskoj medicinskij zhurnal. 2017;2:27–28. Russian
- Onishchuk AG, Levkovich AA. Lekarstvennye preparaty, primenyaemye pri varikoznom rasshirenii ven. Vestnik nauchnyh konferencij. 2019;6–2 (46):100–101. Russian
- Voronkov AV, Gamzeleva OYu. Review of modern phlebotrophic preparations based on flavonoids as perspective endothelioprotectors in the treatment of chronic diseases of the veins. Ambulatory Surgery. 2019;(1-2):27–33. doi: 10.21518/1995-1477-2019-1-2-27-33. Russian
- Akhmetzyanov RV, Bredikhin RA. Clinical efficacy of Detralex in the treatment of patients with varicose veins of the pelvis. Angiology and vascular surgery. 2018;24(2):1–6. Russian
- Coleridge-Smith P, Lok C, Ramelet AA. Venous leg ulcer: a meta-analysis of adjunctive therapy with micronized purified flavonoid fraction. European Journal of Vascular and Endovascular Surgery. 2005; 30: 198-208.
- Savelyeva MI, Sychev DA. Possibilities of pharmacokinetic modeling of venotonics on the example of bioflavonoids. Angiology and vascular surgery. 2018;24(4):76–80. Russian
- Cao R, Zhao Y, Zhou Z, Zhao X. Enhancement of the water solubility and antioxidant activity of hesperidin by chitooligosaccharide. J Sci Food Agric. 2018;98(6):2422–2427. doi: 10.1002/jsfa.8734.
- Paysant J, Sansilvestri-Morel P, Bouskela E, Verbeuren TJ. Different flavonoids present in the micronized purified flavonoid fraction (Daflon 500 mg) contribute to its anti-hyperpermeability effect in the hamster cheek pouch microcirculation. Int. Angiol. 2008;27(1):81–85.
- ZHuravleva MV, Serebrova SYu, Prokof’ev AB, Ponomarenko TM, Demchenkova EYu, Gorodeckaya GI. Modern venotonics: possibilities of clinical pharmacology and pharmacotherapy. Attending doctor. 2017;7:25.
- Zupanets I, Shebeko S, Zimin S. Comparative study of the original technology of micronization of the purified flavonoid fraction “Detralex®” and the technology of micronization of drugs D and N of Ukrainian manufacturers. Asian Journal of Pharmaceutical and Clinical Research. 2018;11:10–15.
- Korolev AV. Assessment of pharmaceutical equivalence of drugs at the stage of their registration. Khim.-farm. zhurnal. 2009;43(3):49–52. Russian
- Garner RC, Garner JV, Gregory S, Whattam M, Calam A, Leong D. Comparison of the absorption of micronized (Daflon 500 mg) and nonmicronized 14C-diosmin tablets after oral administration to healthy volunteers by accelerator mass spectrometry and liquid scintillation counting. J Pharm Sci. 2002;91(1):32–40. doi: 10.1002/jps.1168.
- Arzamastsev AP, Dorofeev VL. Equivalence of generic drugs: pharmaceutical aspects. Vedomosti NTs ESMP. 2007;1:6–11. Russian
- Belousov YuB. The issue of equivalence of original and reproduced drugs from the standpoint of a clinical pharmacologist. Vedomosti NTs ESMP. 2007;1:32–36. Russian
- Bagirova VL, Kiseleva GS, Tentsova AI. Methodical guidelines for the development of the “Dissolution” test for individual drugs. Farmateka. 1997;1:39–40. Russian
- Smekhova IE, Vainshtein VA, Ladutko YuM, Druzhininskaya OV, Turetskova NN. Disintegrants and their influence on the dissolution of substances of different classes according to the biopharmaceutical classification system. Development and registration medicines. 2018;4:62–72. Russian
- The State Pharmacopoeia of the Russian Federation. Ministry of Health of the Russian Federation. XIV ed., Vol. 2, Moscow, 2018. P. 2164–2182. OFS.1.4.1.0015.15. Dissolution for solid dosage forms. Available at: http://femb.ru/femb/pharmacopea.php (Last accessed: September 15, 2018). Russian
- Trofimov SV, Stepanova EF. Glibenclamide dosage forms: modern technologies for solving urgent issues. Development and registration of drugs. 2014;2(7):64–67. Russian
- Szeleszczuk Ł, Pisklak DM, Zielińska-Pisklak M, Wawer I. Spectroscopic and structural studies of the diosmin monohydrate and anhydrous diosmin. Int J Pharm. 2017;529(1–2):193–199. doi: 10.1016/j.ijpharm.2017.06.078.
Supplementary files
