The roots of yellow gentian, Gentiana lutea L. (Gentianaceae) are used in traditional medicine for the treatment of gastrointestinal disorders, with the literature data indicate a local gastric effect of gentian root extract (GRE) and support the use of the solid pharmaceutical forms. Gentiopicroside, as a dominant secoiridoid in the GRE, has a short elimination half-life and low bioavailability and, consequently, its bioactivity is limited. The aim of the study was to develop gastroretentive floating delivery system with GRE, and to provide prolonged release of gentiopicroside. Floating granules with dry GRE (DGRE) were prepared by the hot-melt granulation technique, while formulations included effervescent components (citric acid and sodium bicarbonate), hydroxypropyl methylcellulose (HPMC) and meltable binders (Compritol® 888 ATO and Gelucire® 50/13). The flowability of the DGRE and prepared formulations was determined by calculating the Carr index and Hausner ratio. Floating properties and in vitro dissolution rate of gentiopicroside from investigated formulations were examined. Floating granules were characterized with improved flowability (Carr index 14-22 %; Hausner ratio 1.16-1.28) in comparison to the DGRE (Carr index 28.99 %; Hausner ratio of 1.41). Furthermore, the floating granules exhibited immediate and long-lasting buoyancy and prolonged-release of gentiopicroside (over 8 h). Compritol® 888 ATO has provided sustained release of gentiopicroside from floating granules, while HPMC has decreased release rate additionally. On the other hand, Gelucire® 50/13 has increased gentiopicroside release rate. The results have shown that hot-melt granulation technique, as a green granulation method was successfully employed for obtaining gastroretentive floating granules with DGRE.
Aoki, H., Iwao, Y., Mizoguchi, M., Noguchi, S., & Itai, S. (2015). Clarithromycin highly-loaded gastro-floating fine granules prepared by high-shear melt granulation can enhance the efficacy of Helicobacter pylori eradication. European Journal of Pharmaceutics and Biopharmaceutics, 92, 22–27.
Balijagić, J., Janković, T., Zdunić, G., Bošković, J., Šavikin, K., Gođevac, D., & Menković, N. (2012). Chemical profile, radical scavenging and cytotoxic activity of yellow gentian leaves (Genitaneae luteae folium) grown in northern regions of Montenegro. Natural Product Communications, 7(11), 1934578 1200701119.
European Medicines Agency. (2018). report on Gentiana lutea L., radix Ref.: EMA/HMPC/607863/2017.
European Pharmacopoeia 10th edition. (n.d.). Strasbourg; Council of Europe.
Khaled, A., Abdel-Hamid, S., Nasr, M., & Sammour, O. A. (2020). Fabrication of extended-dissolution divalproex tablets: a green solvent-free granulation technique. Drug Development and Industrial Pharmacy, 1–38.
Kim, J. I., Park, S. W., Lim, J. J., Sohn, S. I., Shin, J. S., Park, S. C., & Lee, K. T. (2017). Gastroprotective effects of the isopropanol extract of Artemisia princeps and its gastroretentive floating tablets on gastric mucosal injury. Acta Pharmaceutica, 67(4), 479–494.
Knezevic, Z., Gosak, D., Hraste, M., Rausl, D., & Khan, M. Z. I. (2009). Application of hot-melt coating process for designing a lipid based controlled release drug delivery system for highly aqueous soluble drugs. Chemical and Pharmaceutical Bulletin, 57(5), 464–471.
Krylova, S. G., Turetskova, V. F., Makarova, O. G., & Zueva, E. P. (2018). Technology development and antiulcer activity of gastroretentive tablets with aspen bark dry extract. Pharmaceutical Chemistry Journal, 52(2), 133–138.
Li, S., Lin, S., Daggy, B. P., Mirchandani, H. L., & Chien, Y. W. (2003). Effect of HPMC and Carbopol on the release and floating properties of Gastric Floating Drug Delivery System using factorial design. International Journal of Pharmaceutics, 253(1–2), 13–22.
Lopes, C. M., Bettencourt, C., Rossi, A., Buttini, F., & Barata, P. (2016). Overview on gastroretentive drug delivery systems for improving drug bioavailability. International Journal of Pharmaceutics, 510(1), 144–158.
Mathew, A., Taranalli, A. D., & Torgal, S. S. (2004). Evaluation of anti-inflammatory and wound healing activity of Gentiana lutea rhizome extracts in animals. Pharmaceutical Biology, 42(1), 8–12.
Menkovic, N., Juranic, Z., Stanojkovic, T., Raonic‐Stevanovic, T., Šavikin, K., Zdunić, G., & Borojevic, N. (2010). Radioprotective activity of Gentiana lutea extract and mangiferin. Phytotherapy Research, 24(11), 1693–1696.
Mishra, R., & Dhole, S. (2019). Lipid-based floating multiparticulate delivery system for bioavailability enhancement of berberine hydrochloride. Journal of Applied Pharmaceutical Science, 9(11), 036–047.
Mudrić, J., Janković, T., Šavikin, K., Bigović, D., Đukić-Ćosić, D., Ibrić, S., & Đuriš, J. (2020). Optimization and modelling of gentiopicroside, isogentisin and total phenolics extraction from Gentiana lutea L. roots. Industrial Crops and Products, 155, 112767.
Niiho, Y., Yamazaki, T., Nakajima, Y., Yamamoto, T., Ando, H., Hirai, Y., & Ida, Y. (2006). Gastroprotective effects of bitter principles isolated from Gentian root and Swertia herb on experimentally-induced gastric lesions in rats. Journal of Natural Medicines, 60(1), 82–88.
Öztürk, N., Can Başer, K. H., Aydin, S., Öztürk, Y., & Çaliş, I. (2002). Effects of Gentiana lutea ssp. symphyandra on the central nervous system in mice. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 16(7), 627–631.
Öztürk, N., Herekman-Demir, T., Öztürk, Y., Bozan, B., & Başer, K. H. C. (1998). Choleretic activity of Gentiana lutea ssp. symphyandra in rats. Phytomedicine, 5(4), 283–288.
Patel, A. U., Caudhari, D. V., Shah, P. J., & Shah, S. A. (2018). Hot melt granulation method for the preparation of floating matrix tablets of Tolperison Hydrochloride. Future Journal of Pharmaceutical Sciences, 4(2), 139–149.
Pontus, S., A.P., M., & Chaim, I. (2006). Use of Gentiana lutea extracts as an antimicrobial agent. European Patent EP1663271.
Prasanthi, N. L. (2019). Design and Development of Gastroretentive Tablets of Coccinia grandis leaf extract for treating Helicobacter pylori infection. Asian Journal of Pharmaceutics (AJP): Free Full Text Articles from Asian J Pharm, 13(3).
Šavikin, K., Aljančić, I. S., Vajs, V. E., Milosavljević, S. M., Jadranin, M., Đorđević, I., & Menković, N. R. (2015). Bioactive secondary metabolites in several genera of gentianaceae species from thè central regions of thè balkan peninsula. In The Gentianaceae-Volume 2: Biotechnology and Applications (pp. 319–347).
Setthacheewakul, S., Kedjinda, W., Maneenuan, D., & Wiwattanapatapee, R. (2011). Controlled release of oral tetrahydrocurcumin from a novel self-emulsifying floating drug delivery system (SEFDDS. Aaps Pharmscitech, 12(1), 152–164.
Shah, S. H., Patel, J. K., & Patel, N. V. (2009a). Gastroretentive floating drug delivery systems with potential herbal drugs for Helicobacter pylori eradication: a review. Journal of Chinese Integrative Medicine, 7(10), 976–982.
Shah, S. H., Patel, J. K., & Patel, N. V. (2009b). Gastroretentive floating drug delivery systems with potential herbal drugs for Helicobacter pylori eradication: a review. Journal of Chinese Integrative Medicine, 7(10), 976–982.
Shimpi, S., Chauhan, B., Mahadik, K. R., & Paradkar, A. (2004). Preparation and evaluation of diltiazem hydrochloride-Gelucire 43/01 floating granules prepared by melt granulation. AAPS PharmSciTech, 5(3), 51–56.
Tripathi, J., Thapa, P., Maharjan, R., & Jeong, S. H. (2019). Current state and future perspectives on gastroretentive drug delivery systems. Pharmaceutics, 11(4), 193.
Wang, C. H., Wang, Z. T., Bligh, W. A., White, K. N., & White, C. J. B. (2004). Pharmacokinetics and tissue distribution of gentiopicroside following oral and intravenous administration in mice. European Journal of Drug Metabolism and Pharmacokinetics, 29(3), 199–203.
Wu, S., Yang, L., Sun, W., Si, L., Xiao, S., Wang, Q., & Zhang, Y. (2017). Design, synthesis and biological evaluation of gentiopicroside derivatives as potential antiviral inhibitors. European Journal of Medicinal Chemistry, 130, 308–319.
Yusif, R. M., Hashim, I. I. A., Mohamed, E. A., & Badria, F. A. E. (2016). Gastroretentive matrix tablets of Boswellia oleogum resin: preparation, optimization, in vitro evaluation, and cytoprotective effect on indomethacin-induced gastric ulcer in rabbits. Aaps Pharmscitech, 17(2), 328–338.
Zhai, H., Jones, D. S., McCoy, C. P., Madi, A. M., Tian, Y., & Andrews, G. P. (2014). Gastroretentive extended-release floating granules prepared using a novel fluidized hot melt granulation (FHMG) technique. Molecular Pharmaceutics, 11(10), 3471–3483.
Zhang, Y., Zhang, L., Zhang, Q., Zhang, X., Zhang, T., & Wang, B. (2018). Enhanced gastric therapeutic effects of Brucea javanica oil and its gastroretentive drug delivery system compared to commercial products in pharmacokinetics study. Drug Design, Development and Therapy, 12, 535.
Živković, J., Janković, T., Menković, N., & Šavikin, K. (2019). Optimization of ultrasound-assisted extraction of isogentisin, gentiopicroside and total polyphenols from gentian root using response-surface methodology. Industrial Crops and Products, 139, 111567.
Citation
Copyright
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The statements, opinions and data contained in the journal are solely those of the individual authors and contributors and not of the publisher and the editor(s). We stay neutral with regard to jurisdictional claims in published maps and institutional affiliations.
