Comprehensive study for the development of rectal suppositories with diosmin and hesperidin




suppositories, diosmin, hesperidin, hemorrhoids, biphasic-type system, pharmacological activity, release profile, technological parameters, quantitative determination


The aim. To conduct a comprehensive study of biphasic-type suppositories that contain diosmin and hesperidin.

Materials and methods. Samples of biphasic-type suppositories with a mass of 4.0 were objects of the study. Pharmacological, technological and analytical research methods were used to directly or indirectly analyze the strength and completeness of the drug activity. Thus, in this work we combined the study of the specificity of the pharmacological action of the drug, experimental verification of the quantitative content of API, analysis of the structural properties of suppositories and study of the profile of the release of active pharmaceutical ingredients.

Results. Therefore, based on the obtained data, the most effective dose was 75 mg / kg (in terms of a human dose of 300 mg per suppository). The drug in the selected dose showed a significant therapeutic effect, which significantly exceeded that of the test sample at a lower dose and the reference agent. According to the results of technological studies, it was determined that all samples of suppositories had satisfactory structural and mechanical properties. Studies of the histological structure of the mucous membrane of rats proved that there is a positive effect of treatment with suppositories with diosmin and hesperidin due to the improvement of the normal condition of the mucous membrane, the absence of edema and ulcerative defect. Research of the release profile of active pharmaceutical ingredients showed that the best percentage of release is characteristic of sample 2 (99.8 %)

Conclusions. Therefore, suppositories with diosmin and hesperidin in therapeutically dose of 75 mg/kg of animal weight can be used for further research and will be of interest in the treatment of hemorrhoids of both acute and chronic forms

Author Biographies

Yelyzaveta Borko, National University of Pharmacy

Postgraduate Student

Department of Industrial Technology of Drugs

Inna Kovalevska, National University of Pharmacy

Doctor of Pharmaceutical Sciences, Associate Professor

Department of Industrial Technology of Drugs

Volodymyr Grudko, National University of Pharmacy

PhD, Assistant Professor

Department of Pharmaceutical Chemistry

Nadiia Kononenko, National University of Pharmacy

Doctor of Pharmaceutical Sciences, Professor, Head of Department

Department Normal and pathological physiology

Mariia Velya, National University of Pharmacy

Postgraduate Student

Department of Industrial Technology of Drugs


  1. Lohsiriwat, V. (2012). Hemorrhoids: From basic pathophysiology to clinical management. World Journal of Gastroenterology, 18 (17), 2009–2017. doi:
  2. Sanchez, C., Chinn, B. (2011). Hemorrhoids. Clinics in Colon and Rectal Surgery, 24(01), 5–13. doi:
  3. Cirocco, W. C. (2018). Reprint of: Why are hemorrhoids symptomatic? the pathophysiology and etiology of hemorrhoids. Seminars in Colon and Rectal Surgery, 29 (4), 160–166. doi:
  4. Havaldar, V. D., Yadav, A. V., Dias, R. J., Mali, K. K., Ghorpade, V. S., Salunkhe, N. H. (2015). Rectal suppository as an effective alternative for oral administration. Research Journal of Pharmacy and Technology, 8 (6), 759–766. doi:
  5. Hermann, J., Hermann, T. (2020). Bioavailability of drugs from suppositories in clinical practice after 1995. Acta Poloniae Pharmaceutica – Drug Research, 77 (3), 417–421. doi:
  6. Purohit, T. J., Hanning, S. M., Wu, Z. (2018). Advances in rectal drug delivery systems. Pharmaceutical Development and Technology, 23 (10), 942–952. doi:
  7. Yarnykh, T. G., Tolochko, E. V., Chushenko, V. N. (2011). Drug synthesis methods and manufacturing technology. Pharmaceutical Chemistry Journal, 44 (10), 551–556. doi:
  8. Gladukh, I., Podorozhna, M. (2021). Study of structural and mechanical properties of sodium alginate gels. EUREKA: Health Sciences, 2, 82–89. doi:
  9. Borko, Y., Kovalevska, I. (2019). Studies of physico-chemical and pharmaco-technological parameters of bioflavonoids diosmin and hesperidin. ScienceRise: Pharmaceutical Science, 5 (21), 42–46. doi:
  10. Ye. Borko, I. Kovalevska, O. Ruban. (2019). The Marketing Research of the Pharmaceutical Market of Ukraine about the Prospects of Creation a New Medical Form. Herald of the Economic Sciences of Ukraine, 2 (37), 137–142. doi:
  11. Corsale, I., Carrieri, P., Martellucci, J., Piccolomini, A., Verre, L., Rigutini, M., Panicucci, S. (2018). Flavonoid mixture (diosmin, troxerutin, rutin, hesperidin, quercetin) in the treatment of I–III degree hemorroidal disease: a double-blind multicenter prospective comparative study. International Journal of Colorectal Disease, 33 (11), 1595–1600. doi:
  12. Giannini, I., Amato, A., Basso, L., Tricomi, N., Marranci, M., Pecorella, G. et. al. (2015). Flavonoids mixture (diosmin, troxerutin, hesperidin) in the treatment of acute hemorrhoidal disease: a prospective, randomized, triple-blind, controlled trial. Techniques in Coloproctology, 19 (6), 339–345. doi:
  13. Karetová, D., Suchopár, J., Bultas, J. (2020). Diosmin/hesperidin: a cooperating tandem, or is diosmin crucial and hesperidin an inactive ingredient only? Vnitřní Lékařství, 66 (2), 97–103. doi:
  14. Zhang, Z. (2019). The Effectiveness of Combined Drug Delivery Systems. Journal of Drug Delivery and Therapeutics, 9 (1-s), 377–380. doi:
  15. Purohit, T. J., Hanning, S. M., Wu, Z. (2018). Advances in rectal drug delivery systems. Pharmaceutical Development and Technology, 23 (10), 942–952. doi:
  16. Salova, V. G., Kozlova, Z. M., Odintsova, E. B. (2019). Development of the Optimal Diphilic Emulsion Compositions for Phytoextract Suppositories. Pharmaceutical Chemistry Journal, 52 (12), 996–1000. doi:
  17. Fatmi, S., Taouzinet, L., Lahiani-Skiba, M., Skiba, M., Iguer-Ouada, M. (2021). New Formulation and Evaluation of Camptothecin Encapsulated and/or Dispersed Suppository. Anti-Cancer Agents in Medicinal Chemistry, 21 (9), 1183–1190. doi:
  18. Shelke, O., Kulkarni, A. (2019). Formulation, Development and Evaluation of Nifedipine Emulgel for Treatment of Anal Fissures Using Polymeric Emulsifiers. Indian Journal of Pharmaceutical Education and Research, 53 (2s), s74–s81. doi:
  19. Szekalska, M., Puciłowska, A., Szymańska, E., Ciosek, P., Winnicka, K. (2016). Alginate: Current Use and Future Perspectives in Pharmaceutical and Biomedical Applications. International Journal of Polymer Science, 2016, 1–17. doi:
  20. Fu, S., Thacker, A., Sperger, D. M., Boni, R. L., Buckner, I. S., Velankar, S. et. al. (2011). Relevance of Rheological Properties of Sodium Alginate in Solution to Calcium Alginate Gel Properties. AAPS PharmSciTech, 12 (2), 453–460. doi:
  21. European Pharmacopoeia (2016). Strasbourg: Council of Europe.
  22. Maslii, Y., Ruban, O., Kasparaviciene, G., Kalveniene, Z., Materiienko, A., Ivanauskas, L. et. al. (2020). The Influence of pH Values on the Rheological, Textural and Release Properties of Carbomer Polacril® 40P-Based Dental Gel Formulation with Plant-Derived and Synthetic Active Components. Molecules, 25 (21), 5018–5034. doi:
  23. Derzhavna Farmakopeia Ukrainy. Vol. 1 (2015). Kharkiv: DP «Ukrainskyi naukovyi farmakopeinyi tsentr yakosti likarskykh zasobiv», 1128.
  24. Zaghloul, A.-A., Lila, A., Abd-Allah, F., Nada, A. (2017). Preparation and in vitro/in vivo evaluation of metformin hydrochloride rectal dosage forms for treatment of patients with type II diabetes. Journal of Drug Targeting, 25 (5), 463–470. doi:
  25. Smith, A. J., Clutton, R. E., Lilley, E., Hansen, K. E. A., Brattelid, T. (2017). PREPARE: guidelines for planning animal research and testing. Laboratory Animals, 52 (2), 135–141. doi:
  26. Isimi, C. Y., John-africa, L. B., Ekere, K. E., Olayemi, O. J., Aremu, O. I., Emeje, M. O. (2021). Formulation, evaluation and anti-hemorroidal activity of suppositories containing moringa oleifera lam. seed oil. ACTA Pharmaceutica Sciencia, 59 (1), 113–131. doi:
  27. Suvarna, K. S., Layton, C., Bancroft, J. D. (2018). Bancroft's Theory and Practice of Histological Techniques E-Book. Elsevier, 558.
  28. Khan, A., Singh, L. (2016). Various techniques of bioavailibility enhancement: a review. Journal of Drug Delivery and Therapeutics, 6 (3), 34–41. doi:
  29. Hua, S. (2019). Physiological and Pharmaceutical Considerations for Rectal Drug Formulations. Frontiers in Pharmacology, 10. doi:
  30. Jug, M., Hafner, A., Lovrić, J., Kregar, M. L., Pepić, I., Vanić, Ž. et. al. (2018). An overview of in vitro dissolution/release methods for novel mucosal drug delivery systems. Journal of Pharmaceutical and Biomedical Analysis, 147, 350–366. doi:
  31. Belniak, P., Świąder, K., Szumiło, M., Hyla, A., Poleszak, E. (2017). Comparison of physicochemical properties of suppositories containing starch hydrolysates. Saudi Pharmaceutical Journal, 25 (3), 365–369. doi:
  32. Havaldar, V. D., Yadav, A. V., Dias, R. J., Mali, K. K., Survase, A. B., Ghorpade, V. S., Salunkhe, N. H. (2017). Screening of Suppository bases for Rectal delivery of Carbamazepine. Research Journal of Pharmacy and Technology, 10 (8), 2697–2703. doi:
  33. Salman, Z. D., Alhamdany, A. T., Yousif, N. Z. (2020). An Innovative Mucoadhesive Thermosensitive In situ Gelling Liquid Suppository of Metoclopramide Hydrocloride for Treatment of Nausea and Vomiting Associated with Diseases. Indian Journal Of Pharmaceutical Sciences, 82 (4), 650–664. doi:
  34. Hecht, H., Srebnik, S. (2016). Structural Characterization of Sodium Alginate and Calcium Alginate. Biomacromolecules, 17 (6), 2160–2167. doi:
  35. Segale, L., Giovannelli, L., Mannina, P., Pattarino, F. (2016). Calcium Alginate and Calcium Alginate-Chitosan Beads Containing Celecoxib Solubilized in a Self-Emulsifying Phase. Scientifica, 2016, 1–8. doi:
  36. Panche, A. N., Diwan, A. D., Chandra, S. R. (2016). Flavonoids: an overview. Journal of Nutritional Science, 5. doi:
  37. Rao, S. S. C., Tetangco, E. P. (2020). Anorectal Disorders: An Update. Journal of Clinical Gastroenterology, 54 (7), 606–613. doi:




How to Cite

Borko, Y., Kovalevska, I., Grudko, V., Kononenko, N., & Velya, M. (2022). Comprehensive study for the development of rectal suppositories with diosmin and hesperidin. ScienceRise: Pharmaceutical Science, (1(35), 14–21.



Pharmaceutical Science

Most read articles by the same author(s)

1 2 > >>