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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Physical Characterisation and Stability Study of Formulated Chromolaena odorata Gel

Author(s): Qurratul Ain Zakirah Mohd Zamram, Hannis Fadzillah Mohsin, Mashani Mohamad, Nurul Aqmar Mohamad Nor Hazalin and Khuriah Abdul Hamid*

Volume 19, Issue 4, 2022

Published on: 06 January, 2022

Page: [479 - 490] Pages: 12

DOI: 10.2174/1567201818666210419114809

Price: $65

Abstract

Background: Formulation of topical products for skin delivery that fulfill good formulation criteria has always been a challenge for pharmaceutical scientists. Despite the challenges, gelbased drug delivery offers some advantages such that it is non-invasive, painless, involves avoidance of the first-pass metabolism, and has satisfactory patient compliance.

Objectives: In this study, C. odorata gel and quercetin gel (bioactive flavonoid compound) were successfully formulated and compared with placebo and conventional wound aid gel. The chromatographic profiling was conducted to screen the presence of phytoconstituents. Subsequently, all formulated gels were evaluated for physical characteristics and stability.

Methods: Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) of C. odorata methanolic leaves extract showed a distinct compound separation at a retention time of 8.4min to 34.8 min at 254nm. All gels were characterised by evaluating their rheological properties, including storage modulus, loss modulus, and plastic viscosity. Besides, texture analysis was performed to measure the firmness, consistency, cohesiveness, and viscosity index of the gels.

Results: According to the results, C. odorata gel demonstrated better spreadability as compared to the other gels, which required less work and was found to be favourable for application on the skin. Moreover, C. odorata gel showed no changes in organoleptic properties and proven to be stable after 30 days of accelerated stability study at 40°C ± 2°C with Relative Humidity (RH) of 75% ± 5%.

Conclusion: C. odorata gel was found to be stable, reflecting the combination of materials used in the formulation, which did not degrade throughout the study. This work suggests the potential of this gel as a vehicle to deliver the active ingredients of C. odorata to the skin, which can be further explored as a topical application for antimicrobial wound management or other skin diseases study.

Keywords: Chromolaena odorata, physical characterisation, rheology, stability study, organoleptic properties, gel delivery.

Graphical Abstract

[1]
Williams, A.C. Topical and transdermal drug delivery. Aulton’s pharmaceutics: the design and manufacture of medicines, 4th Ed; Aulton, M.E.; Taylor, K.M., Eds.; Churchill Livingstone/Elsevier: United Kingdom, 2013, pp. 676-697.
[2]
Tran, T.N. Cutaneous drug delivery: an update. J. Investig. Dermatol. Symp. Proc., 2013, 16(1), S67-S69.
[http://dx.doi.org/10.1038/jidsymp.2013.28] [PMID: 24326566]
[3]
Tsyurupa, M.P.; Davankov, V.A. Hyper crosslinked polymers: basic principle of preparing the new class of polymeric materials. React. Funct. Polym., 2002, 53(2-3), 193-203.
[http://dx.doi.org/10.1016/S1381-5148(02)00173-6]
[4]
Ren, X.; Wang, N.; Zhou, Y.; Song, A.; Jin, G.; Li, Z.; Luan, Y. An injectable hydrogel using an immunomodulating gelator for amplified tumor immunotherapy by blocking the arginase pathway. Acta Biomater., 2021, S1742-7061(21)00069-6.
[PMID: 33524560]
[5]
Trombino, S.; Servidio, C.; Curcio, F.; Cassano, R. Strategies for hyaluronic acid-based hydrogel design in drug delivery. Pharmaceutics, 2019, 11(8), E407.
[http://dx.doi.org/10.3390/pharmaceutics11080407] [PMID: 31408954]
[6]
Piana, M.; Silva, M.A.; Trevisan, G.; de Brum, T.F.; Silva, C.R.; Boligon, A.A.; Oliveira, S.M.; Zadra, M.; Hoffmeister, C.; Rossato, M.F.; Tonello, R.; Laporta, L.V.; de Freitas, R.B.; Belke, B.V.; Jesus, R.S.; Ferreira, J.; Athayde, M.L. Antiinflammatory effects of Viola tricolor gel in a model of sunburn in rats and the gel stability study. J. Ethnopharmacol., 2013, 150(2), 458-465.
[http://dx.doi.org/10.1016/j.jep.2013.08.040] [PMID: 24008111]
[7]
Boligon, A.A.; da Rosa Moreira, L.; Piana, M.; de Campos, M.M.A.; Oliveira, S.M. Topical antiedematogenic and anti-inflammatory effect of Scutia buxifolia Reissek gel and stability study. J. Photochem. Photobiol. B, 2017, 167, 29-35.
[http://dx.doi.org/10.1016/j.jphotobiol.2016.12.026] [PMID: 28039787]
[8]
Krongrawa, W.; Limmatvapirat, S.; Pongnimitprasert, N.; Meetam, P.; Limmatvapirat, C. Formulation and evaluation of gels containing coconut kernel extract for topical application. Asian J Pharm Sci, 2018, 13(5), 415-424.
[http://dx.doi.org/10.1016/j.ajps.2018.01.005] [PMID: 32104416]
[9]
Dantas, M.G.B.; Reis, S.A.G.B.; Damasceno, C.M.D.; Rolim, L.A.; Rolim-Neto, P.J.; Carvalho, F.O. Development and evaluation of stability of a gel formulation containing the Monoterpene Borneol. Sci. World. J., 2016, 2016, 7394685.
[http://dx.doi.org/10.1155/2016/7394685]
[10]
Ibrahim, E-S.A.; Hassan, M.A.; El-Mahdy, M.M.; Mohamed, A.S. Formulation and evaluation of quercetin in certain dermatological preparations. J. Drug Deliv. Sci. Technol., 2007, 17(6), 431-436.
[http://dx.doi.org/10.1016/S1773-2247(07)50084-5]
[11]
Chen, M.X.; Alexander, K.S.; Baki, G. Formulation and evaluation of antibacterial creams and gels containing metal ions for topical application. J. Pharm. (Cairo), 2016, 2016, 5754349.
[http://dx.doi.org/10.1155/2016/5754349] [PMID: 27885352]
[12]
Shen, C.; Shen, B.; Liu, X.; Yuan, H. Nanosuspensions based gel as delivery system of nitrofurazone for enhanced dermal bioavailability. J. Drug Deliv. Sci. Technol., 2018, 43, 1-11.
[http://dx.doi.org/10.1016/j.jddst.2017.09.012]
[13]
Al-Muntasheri, G.A.; Hussein, I.A.; Nasr-El-Din, H.A.; Amin, M.B. Viscoelastic properties of a high temperature cross-linked water shut-off polymeric gel. J. Petrol. Sci. Eng., 2007, 55(1-2), 56-66.
[http://dx.doi.org/10.1016/j.petrol.2006.04.004]
[14]
Maitra, J.; Shukla, V.K. Cross-linking in hydrogels - a review. Am. J. Pol. Sci., 2014, 4(2), 25-31.
[15]
Yu, Y.; Zhu, S.; Hou, Y.; Li, J.; Guan, S. Sulfur contents in sulfonated hyaluronic acid direct the cardiovascular cells fate. ACS Appl. Mater. Interfaces, 2020, 12(41), 46827-46836.
[http://dx.doi.org/10.1021/acsami.0c15729] [PMID: 33016070]
[16]
Rai, V.K.; Yadav, N.P.; Sinha, P.; Mishra, N.; Luqman, S.; Dwivedi, H.; Kymonil, K.M.; Saraf, S.A. Development of cellulosic polymer based gel of novel ternary mixture of miconazole nitrate for buccal delivery. Carbohydr. Polym., 2014, 103, 126-133.
[http://dx.doi.org/10.1016/j.carbpol.2013.12.019] [PMID: 24528709]
[17]
Albuquerque, P.B.S.; Coelho, L.C.B.B.; Teixeira, J.A.; Carnero- da-Cunha, M.G. Approaches in biotechnological applications of natural polymers. Mol. Sci., 2016, 3(3), 386-425.
[http://dx.doi.org/10.3934/molsci.2016.3.386]
[18]
Gyles, D.A.; Castro, L.D.; Silva, J.O.C.; Ribeiro-Costa, R.M. A review of the designs and prominent biomedical advances of natural and synthetic hydrogel formulations. Eur. Polym. J., 2017, 88, 373-392.
[http://dx.doi.org/10.1016/j.eurpolymj.2017.01.027]
[19]
Maitz, M.F. Applications of synthetic polymers in clinical medicine. Biosurface Biotribol., 2015, 1(3), 161-176.
[http://dx.doi.org/10.1016/j.bsbt.2015.08.002]
[20]
Hu, X.; Wei, W.; Qi, X.; Yu, H.; Feng, L.; Li, J.; Wang, S.; Zhang, J.; Dong, W. Preparation and characterization of a novel pH-sensitive Salecan-g-poly(acrylic acid) hydrogel for controlled release of doxorubicin. J. Mater. Chem. B Mater. Biol. Med., 2015, 3(13), 2685-2697.
[http://dx.doi.org/10.1039/C5TB00264H] [PMID: 32262916]
[21]
Majid, S.; Bukhari, H.; Khan, S.; Rehanullah, M.; Ranjha, N.M. Synthesis and characterisation of chemically cross-linked acrylic acid / gelatin hydrogels : effect of pH and composition on swelling and drug release. Int. J. Polym. Sci., 2015, 2015
[22]
Ghutepatil, P.; Pawar, S. Surface functionalisation of MNPs for magnetic hyperthermia therapy. In: Progress and prospect in nanoscience today; Pawar, S., Ed.; Nova Science Publisher, Inc: USA, 2020, pp. 219-220.
[23]
Wadetwar, R.N.; Agrawal, A.R.; Kanojiya, P.S. In situ gel containing Bimatoprost solid lipid nanoparticles for ocular delivery: in-vitro and ex-vivo evaluation. J. Drug Deliv. Sci. Technol., 2020, 56, 101575.
[http://dx.doi.org/10.1016/j.jddst.2020.101575]
[24]
Calixto, G.; Yoshii, A.C.; Rocha e Silva, H.; Stringhetti, F.C.B.; Chorilli, M. Polyacrylic acid polymers hydrogels intended to topical drug delivery: preparation and characterization. Pharm. Dev. Technol., 2015, 20(4), 490-496.
[http://dx.doi.org/10.3109/10837450.2014.882941] [PMID: 25975700]
[25]
Simões, A.; Veiga, F.; Vitorino, C. Developing cream formulations : renewed interest in an old problem. J. Pharm. Sci., 2019, 108(10), 3240-3251.
[http://dx.doi.org/10.1016/j.xphs.2019.06.006] [PMID: 31216450]
[26]
Jasnie, F.H. Biological activities and chemical constituents of Chromolaena odorata (L.); King & Robinson. Universiti Malaya, 2009.
[27]
Vijayaraghavan, K.; Rajkumar, J.; Seyed, M.A. Phytochemical screening, free radical scavenging and antimicrobial potential of Chromolaena odorata leaf extracts against pathogenic bacterium in wound infections- a multispectrum perspective. Biocatal. Agric. Biotechnol., 2018, 15, 103-112.
[http://dx.doi.org/10.1016/j.bcab.2018.05.014]
[28]
Aziz, N.A.; Mohamad, M.; Mohsin, H.F.; Mohamad Nor, N.A.; Abdul Hamid, K. The pharmacological properties and medicinal potential of Chromolaena odorata : a review. Int J. Pharm. Nutraceut. Cosmet Sci., 2020, 2, 30-41.
[29]
Atindehou, M.; Lagnika, L.; Guérold, B.; Marc Strub, J.; Zhao, M.; Van Dorsselaer, A. Isolation and identification of two antibacterial agents from Chromolaena odorata L. active against four diarrheal strains. Adv. Microbiol., 2013, 03(01), 115-121.
[http://dx.doi.org/10.4236/aim.2013.31018]
[30]
Ezenyi, I.C.; Salawu, O.A.; Kulkarni, R.; Emeje, M. Antiplasmodial activity-aided isolation and identification of quercetin-4′-methyl ether in Chromolaena odorata leaf fraction with high activity against chloroquine-resistant Plasmodium falciparum. Parasitol. Res., 2014, 113(12), 4415-4422.
[http://dx.doi.org/10.1007/s00436-014-4119-y] [PMID: 25199554]
[31]
Hanh, T.T.H.; Hang, D.T.T.; Van Minh, C.; Dat, N.T. Anti-inflammatory effects of fatty acids isolated from Chromolaena odorata. Asian Pac. J. Trop. Med., 2011, 4(10), 760-763.
[http://dx.doi.org/10.1016/S1995-7645(11)60189-2] [PMID: 22014728]
[32]
Vijayaraghavan, K.; Rajkumar, J.; Seyed, M.A. Efficacy of Chromolaena odorata leaf extracts for the healing of rat excision wounds. Vet. Med. (Praha), 2017, 62(10), 565-578.
[http://dx.doi.org/10.17221/161/2016-VETMED]
[33]
Pandith, H.; Thongpraditchote, S.; Wongkrajang, Y.; Gritsanapan, W. In vivo and in vitro hemostatic activity of Chromolaena odorata leaf extract. Pharm. Biol., 2012, 50(9), 1073-1077.
[http://dx.doi.org/10.3109/13880209.2012.656849] [PMID: 22881138]
[34]
Pandith, H.; Zhang, X.; Liggett, J.; Min, K-W.; Gritsanapan, W.; Baek, S.J. Hemostatic and wound healing properties of Chromolaena odorata leaf extract. ISRN Dermatol., 2013, 2013, 168269.
[http://dx.doi.org/10.1155/2013/168269] [PMID: 23984087]
[35]
Nath, L.R.; Gorantla, J.N.; Joseph, S.M.; Antony, J.; Thankachan, S.; Menon, D.B. Kaempferide, the most active among the four flavonoids isolated and characterised from Chromolaena odorata, induces apoptosis in cervical cancer cells while being pharmacologically safe. RSC Adv., 2015, 5(122), 100912-100922.
[http://dx.doi.org/10.1039/C5RA19199H]
[36]
Chen, H.; Zuo, Y.; Deng, Y. Separation and determination of flavonoids and other phenolic compounds in cranberry juice by high-performance liquid chromatography. J. Chromatogr. A, 2001, 913(1-2), 387-395.
[http://dx.doi.org/10.1016/S0021-9673(00)01030-X] [PMID: 11355837]
[37]
Sharifuldin, M.M.A.; Ismail, Z.; Aisha, A.F.A.; Seow, E.K.; Beh, H.K. Quantification of rutin, quercitrin and quercetin in Cosmos caudatus Kunth by reverse phase high performance liquid chromatography. Qual. Assur. Saf. Crops Foods, 2016, 8(4), 617-622.
[http://dx.doi.org/10.3920/QAS2015.0839]
[38]
Wang, W.; Sun, C.; Mao, L.; Ma, P.; Liu, F.; Yang, J. The biological activities, chemical stability, metabolism and delivery systems of quercetin: A review. Trends Food Sci. Technol., 2016, 56, 21-38.
[http://dx.doi.org/10.1016/j.tifs.2016.07.004]
[39]
ICH Committee. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. StabilityTesting of New Drug Substances and Products Q1A (R2), 2003.
[40]
Hu, Z.; Haruna, M.; Gao, H.; Nourafkan, E.; Wen, D. Rheological properties of partially hydrolysed polyacrylamide seeded by nanoparticles. Ind. Eng. Chem. Res., 2017, 56(12), 3456-3463.
[http://dx.doi.org/10.1021/acs.iecr.6b05036]
[41]
Putri, D.A.; Fatmawati, S. A new flavanone as a potent antioxidant isolated from Chromolaena odorata L. leaves. Evid. Based Complement. Alternat. Med., 2019, 2019, 1453612.
[http://dx.doi.org/10.1155/2019/1453612] [PMID: 31316568]
[42]
Kumar, S; Pandey, AK Chemistry and biological activities of flavonoids: an overview. Sci World J, 2013, 2013, 162750.
[http://dx.doi.org/10.1155/2013/162750]
[43]
Stalikas, C.D. Extraction, separation, and detection methods for phenolic acids and flavonoids. J. Sep. Sci., 2007, 30(18), 3268-3295.
[http://dx.doi.org/10.1002/jssc.200700261] [PMID: 18069740]
[44]
Bonacucina, G.; Martelli, S.; Palmieri, G.F. Rheological, mucoadhesive and release properties of Carbopol gels in hydrophilic cosolvents. Int. J. Pharm., 2004, 282(1-2), 115-130.
[http://dx.doi.org/10.1016/j.ijpharm.2004.06.012] [PMID: 15336387]
[45]
Hespeler, D.; Knoth, D.; Keck, C.M.; Müller, R.H.; Pyo, S.M. smartPearls® for dermal bioavailability enhancement - Long-term stabilization of suspensions by viscoelasticity. Int. J. Pharm., 2019, 562, 293-302.
[http://dx.doi.org/10.1016/j.ijpharm.2019.03.016] [PMID: 30853483]
[46]
Mendonsa, N.S.; Murthy, S.N.; Hashemnejad, S.M.; Kundu, S.; Zhang, F.; Repka, M.A. Development of poloxamer gel formulations via hot-melt extrusion technology. Int. J. Pharm., 2018, 537(1-2), 122-131.
[http://dx.doi.org/10.1016/j.ijpharm.2017.12.008] [PMID: 29253585]
[47]
Murata, H. Rheology - theory and application to biomaterials. Polymerisation; , 2012, pp. 403-425.
[48]
Song, J.; Fan, W.; Long, X.; Zhou, L.; Wang, C.; Li, G. Rheological behaviors of fluorinated hydrophobically associating cationic guar gum fracturing gel. J. Petrol. Sci. Eng., 2016, 146, 999-1005.
[http://dx.doi.org/10.1016/j.petrol.2016.08.013]
[49]
Chang, R-K.; Raw, A.; Lionberger, R.; Yu, L. Generic development of topical dermatologic products: formulation development, process development, and testing of topical dermatologic products. AAPS J., 2013, 15(1), 41-52.
[http://dx.doi.org/10.1208/s12248-012-9411-0] [PMID: 23054971]
[50]
Belda, R.; Herraez, J.V.; Diez, O. Rheological study and thermodynamic analysis of the binary system (water/ethanol): influence of concentration. Phys. Chem. Liquids, 2004, 42(5), 467-479.
[http://dx.doi.org/10.1080/00319100410001700850]
[51]
Zhou, Y.; Wu, L.; Tian, Y.; Li, R.; Zhu, C.; Zhao, G. A novel low-alkali konjac gel induced by ethanol to modulate sodium release. Food Hydrocoll., 2020, 103, 105653.
[http://dx.doi.org/10.1016/j.foodhyd.2020.105653]
[52]
Shukr, M.; Shalaby, S. The influence of the type and concentration of alcohol on the rheological and mucoadhesive properties of carbopol 940 hydroalcoholic gels. Pelagia Res Libr., 2011, 2(6), 161-171.
[53]
Cassanelli, M.; Norton, I.; Mills, T. Effect of alcohols on gellan gum gel structure : Bridging the molecular level and the three-dimensional network. Food Struct., 2017, 14, 112-120.
[http://dx.doi.org/10.1016/j.foostr.2017.09.002]
[54]
Hermansson, E.; Schuster, E.; Lindgren, L.; Altskär, A.; Ström, A. Impact of solvent quality on the network strength and structure of alginate gels. Carbohydr. Polym., 2016, 144(144), 289-296.
[http://dx.doi.org/10.1016/j.carbpol.2016.02.069] [PMID: 27083820]
[55]
Sharma, S.; Pawar, S.; Jain, U.K. Development and evaluation of topical gel of curcumin from different combination of polymers formulation and evaluation of herbal gel. Int. J. Pharm. Pharm. Sci., 2012, 4(4), 452-456.
[56]
Hurler, J.; Engesland, A.; Kermany, B.P.; Skalko-Basnet, N. Improved texture analysis for hydrogel characterisation : Gel cohesiveness, adhesiveness, and hardness. J. Appl. Polym. Sci., 2011, 125, 180-188.
[http://dx.doi.org/10.1002/app.35414]
[57]
Garg, A.; Aggarwal, D.; Garg, S.; Singla, A.K. Spreading of semisolid formulations: an update. Pharm. Technol., 2002, 26(9), 84-105.
[58]
Spina, C.J.; Notarandrea-Alfonzo, J.; Hay, M.; Ladhani, R.; Huszczynski, S.; Khursigara, C.; Precht, R. Silver oxynitrate gel formulation for enhanced stability and antibiofilm efficacy. Int. J. Pharm., 2020, 580, 119197.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119197] [PMID: 32145339]
[59]
Magari, R.T. Assessing shelf life using real-time and accelerated stability tests. Biopharm. Int., 2003, 16(11), 36-48.
[60]
Bajaj, S.; Sakhuja, N.; Singla, D. Stability testing of pharmaceutical products. J. Appl. Pharm. Sci., 2012, 2(3), 129-138.
[61]
Ramadon, D.; Anwar, E.; Harahap, Y. In vitro penetration and bioavailability of novel transdermal quercetin-loaded ethosomal gel. Indian J. Pharm. Sci., 2018, 79(6), 948-956.

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