Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Synthesis, Formulation and Analytical Method Validation of Rutin Derivative

Author(s): Murad Abualhasan*, Mohyeddin Assali, Nidal Jaradat and Tala Sarhan

Volume 16, Issue 6, 2019

Page: [685 - 695] Pages: 11

DOI: 10.2174/1570180816666181108114706

Price: $65

Abstract

Background: In this study; we aimed to increase water solubility and formula dissolution through synthesizing more soluble chemical derivative of rutin.

Objective: The synthesized rutin derivative is novel and shows an improvement in solubility and hence possibly a better oral bioavailability. The steps followed in this study are of major benefit which can be utilized by herbal and pharmaceutical industries to improve their products.

Methods: In this study, a selective partial acetylation was performed to produce a hexaacetylated ester of rutin. Water solubility of the synthesized hexaacetylated ester of rutin and its dissolution were tested and compared to the original rutin. A simple UV/Vis spectrophotometric method was developed and validated.

Results: Water solubility and dissolution profile of hexaacetylated ester derivative of rutin were increased by approximately two folds compared to that of the original rutin. The antioxidant activity of the synthesized derivative was comparable to original rutin. The developed analytical method was found to be linear, accurate, precise, robust and capable of quantifying the active ingredient at low concentration (0.0259 mg/ml).

Conclusion: An improvement in the solubility of rutin was achieved. The tablet formulation of the partially acetylated ester derivative of rutin gives a better dissolution over the marketed rutin tablets.

Keywords: Hexaacetylated Rutin, solubility, dissolution, validation, UV/Vis spectrophotometry, antioxidant activity.

Graphical Abstract
[1]
Kumar, S.; Pandey, A.K. Chemistry and biological activities of flavonoids: An overview. Sci. World J., 2013, 2013, 1-16.
[2]
Narayana, K.R.; Reddy, M.S.; Chaluvadi, M. Bioflavonoids classification, pharmacological, biochemical effects and therapeutic potential. Int. J. Pharmacol., 2001, 33(1), 2-16.
[3]
Patel, J.M. A review of potential health benefits of flavonoids. Lethbridge Undergrad. Res. J., 2008, 3, 2.
[4]
Rice-Evans, C.; Miller, N.; Paganga, G. Antioxidant properties of phenolic compounds. Trends Plant Sci., 1997, 2(4), 152-159.
[5]
Rice-evans, C.A.; Miller, N.J.; Bolwell, P.G. The relative antioxidant activities of plant-derived polyphenolic flavonoids. Free Radic. Res., 1995, 22(4), 375-383.
[6]
Burda, S.; Oleszek, W. Antioxidant and antiradical activities of flavonoids. J. Agric. Food Chem., 2001, 49(6), 2774-2779.
[7]
Cao, G.; Sofic, E.; Prior, R.L. Antioxidant and pro-oxidant behavior of flavonoids: Structure-activity relationships. Free Radic. Biol. Med., 1997, 22(5), 749-760.
[8]
Van Acker, S.A.; Tromp, M.N.; Griffioen, D.H. Structural aspects of antioxidant activity of flavonoids. Free Radic. Biol. Med., 1996, 20(3), 331-342.
[9]
Merk index. 12th Edition ed. Merk Index. 8456.
[10]
Saija, A.; Scalese, M.; Lanza, M.; Marzullo, D.; Bonina, F.; Castelli, F. Flavonoids as antioxidant agents: Importance of their interaction with bio-membranes. Free Radic. Biol. Med., 1995, 19(4), 481-486.
[11]
Kessler, M.; Ubeaud, G.; Jung, L. Anti‐and pro‐oxidant activity of rutin and quercetin derivatives. J. Pharm. Pharmacol., 2003, 55(1), 131-142.
[12]
Guardia, T.; Rotelli, A.E.; Juarez, A.O.; Pelzer, L.E. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Il farmaco, 2001, 56(9), 683-687.
[13]
Kim, D.W.; Hwang, I.K.; Lim, S.S.; Yoo, K.Y.; Li, H.; Kim, Y.S.; Kwon, D.Y.; Moon, W.K.; Kim, D.W.; Won, M.H. Germinated buckwheat extract decreases blood pressure and nitrotyrosine immunoreactivity in aortic endothelial cells in spontaneously hypertensive rats. Phytother. Res., 2009, 23(7), 993-998.
[14]
Ajay, M. Gilani, A-uH.; Mustafa, M.R. Effects of flavonoids on vascular smooth muscle of the isolated rat thoracic aorta. Life Sci., 2003, 74(5), 603-612.
[15]
Beretz, A. Cazenave. J-P. The effect of flavonoids on blood-vessel wall interactions. Prog. Clin. Biol. Res., 1988, 280, 187.
[16]
Grinberg, L.N.; Rachmilewitz, E.A.; Newmark, H. Protective effects of rutin against hemoglobin oxidation. Biochem. Pharmacol., 1994, 48(4), 643-649.
[17]
Formica, J.V.; Regelson, W. Review of the biology of Quercetin and related bioflavonoids [Review]. Food Chem. Toxicol., 1995, 33(12), 1061-1080.
[18]
Manach, C.; Williamson, G.; Morand, C.; Scalbert, A.; Rémésy, C. Bioavailability and bioefficacy of polyphenols in humans. Review of 97 bioavailability studies. Am. J. Clin. Nutr., 2005, 81(1), 230S-242S.
[19]
Graefe, E.U.; Wittig, J.; Mueller, S.; Riethling, A.K.; Uehleke, B.; Drewelow, B.; Pforte, H.; Jacobasch, G.; Derendorf, H.; Veit, M. Pharmacokinetics and bioavailability of quercetin glycosides in humans. J. Clin. Pharmacol., 2001, 41(5), 492-499.
[20]
Erlund, I.; Kosonen, T.; Alfthan, G. Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. Eur. J. Clin. Pharmacol., 2000, 56(8), 545-553.
[21]
Bergström, C.A.S.; Wassvik, C.M.; Johansson, K. Poorly soluble marketed drugs display solvation limited solubility. J. Med. Chem., 2007, 50(23), 5858-5862.
[http://dx.doi.org/10.1021/jm0706416]
[22]
Wassvik, C.M.; Holmén, A.G.; Draheim, R. Molecular characteristics for solid-state limited solubility. J. Med. Chem., 2008, 51(10), 3035-3039.
[http://dx.doi.org/10.1021/jm701587d]
[23]
Beaumont, K.; Webster, R.; Gardner, I. Design of ester prodrugs to enhance oral absorption of poorly permeable compounds: Challenges to the discovery scientist. Curr. Drug Metab., 2003, 4(6), 461-485.
[24]
Yang, Y.-h.; Aloysius, H.; Inoyama, D.; Chen, Y.; Hu, L.-q. Enzyme-mediated hydrolytic activation of prodrugs. Acta Pharmaceutica Sinica B., 2011, 1(3), 143-159. doi: 10.1016/j.apsb. 2011.08.001.
[25]
Baldisserotto, A.; Vertuani, S.; Bino, A.; De Lucia, D.; Lampronti, I.; Milani, R.; Gambari, R.; Manfredini, S. Design, synthesis and biological activity of a novel Rutin analogue with improved lipid soluble properties. Bioorg. Med. Chem., 2015, 23(1), 264-271.
[26]
Abualhasan, M.; Jaradata, N.; Abu-Hasanb, N.; Almasri, M.; Rabbaa, A.; Abu Taha, A. Bioactivity of Viscum album extracts from olive and almond host plants in Palestine. Pharm. J., 2014, 6(2), 38.
[27]
Aulton, M.E. Pharmaceutics: The science of dosage form design. Churchill livingstone, 2002.
[28]
Abualhasan, M.N.; Mansour, J.; Jaradat, N. Formulation and development of a validated uv-spectrophotometric analytical method of rutin tablet. Int. Sch. Res. Notices, 2017, 2017, 7.
[http://dx.doi.org/10.1155/2017/2624947]
[29]
CBER, I. Q2A.; Guideline for Industry.; Text on Validation of Analytical Procedures. March; 1995.
[30]
Guideline, I.H.T. Validation of analytical procedures. Text Methodology., Q2 (R1). 2005; 1.
[31]
Tejal, S.; Solanki, N.; Mahatma, O. Process validation: An essential in the pharmaceutical industry. Inter. J. Pharmace. Res. Develop., 2011, 3(10), 133-142.
[32]
US Pharmacopeial Convention.; Dissolution.; 2012, 711.
[33]
U.S. Pharmacopeia.; Buffer solutions.; 29.
[34]
Lakshmi, C.S.; Badarinath, A. An updated review of dissolution apparatus for conventional and novel dosage forms. Int. J. Pharma. Res. Rev., 2013, 2, 42-53.
[35]
Health UDo.; Services H. Guidance for industry: Dissolution testing of immediate release solid oral dosage forms. Food and Drug Administration Center for Drug Evaluation and Research (CDER). 1997.
[36]
Chang Bioscience.; Inc. [Internet]. Fremont, C.A.; 94538; [cited 2017 Jan 2]. Available from: http://www.changbioscience.com/stat/ ec50.html
[37]
Bakshi, M.; Singh, S. Development of validated stability-indicating assay methods-critical review. J. Pharm. Biomed. Anal., 2002, 28(6), 1011-1040.

© 2024 Bentham Science Publishers | Privacy Policy