Formulation of Nanoemulsion Gel Cayenne Pepper (Capsicum frutescens) Extract as an Anti-inflammatory in Gout Arthritis Pain
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Abstract
Cayenne pepper fruit extract has anti-inflammatory effects and could be a natural remedy of arthritis gout pain. The research aims to find the optimal formula for cayenne pepper extract nanoemulsion gel to improve its permeation capability and assess its effect on inflammation in mice induced by 1.5% carrageenan. Extraction using the maceration method followed by standardizing the extract. The optimal nanoemulsion formula is determined by constructing a pseudo-ternary diagram of the nanoemulsion base. The optimal formula obtained was 80% aquadest, 2% VCO, 18% SMIX (surfactant and cosurfactant). The cayenne pepper extract nanoemulsion is integrated with a gel base followed by evaluation. The extract nanoemulsion has been proven to form globules with a size of 54.4 nm, zeta potential of -23.6 mV, and polydispersity index of 0.403. Exudate volume and TNF-α levels were measured using the air pouch method to assess for anti-inflammatory activity. In comparison to other treatment groups, rats treated with chili pepper extract nanoemulsion gel had the lowest average exudate volume, with a statistically significant difference (DNMRT; P <0.05), according to the results of an ANOVA test combined with Duncan's post-hoc test. Meanwhile, the test for TNF-α levels did not show any significant differences
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References
[1]. Parisa N, Kamaluddin MT, Saleh MI, Sinaga E. The Inflammation Process of Gout Arthritis and its Treatment. J Adv Pharm Technol Res. 2023;14(3):166-70. https://doi.org/10.4103/japtr.japtr_144_23
[2]. Yao R, Geng Z, Mao X, Bao Y, Guo S, Bao L. Tu-Teng-Cao Extract Alleviates Monosodium Urate-Induced Acute Gouty Arthritis in Rats by Inhibiting Uric Acid and Inflammation. Evidence-Based Complementary and Alternative Medicine. 2020;1-13. https://doi.org/10.1155/2020/3095624
[3]. Musta’in Y, Yuniarti T, Rahmasari I, Rahmawati EYC, Saryadi. The effect of warm ginger compress on reducing gout arthritis pain in the elderly. Int J Med Health. 2023;2(4):39-46. https://doi.org/10.55606/ijmh.v2i4.2880
[4]. Singh JA, Gaffo A. Gout epidemiology and comorbidities. Semin Arthritis Rheum. 2020;50(3 Suppl):S11-S16. https://doi.org/10.1016/j.semarthrit.2020.04.008
[5]. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum. 2011;63(10):3136-41. https://doi.org/10.1002/art.30520
[6]. Sholihah FM. Diagnosis and Treatment Gout Artritis. Jurnal Majority. 2014;3(7):39-45.
[7]. Ismail R, Abdullah A, Sangkal A, Toboleu RR. Anti-Inflammatory Activity of Cayenne Pepper (Capsicum frutescens L.) Gel on White Rats (Rattus norvegicus). Journal of Pharmacy and Science. 2022;6(1):59-64. https://doi.org/10.36341/jops.v6i1.3012
[8]. Stanos, SP. Osteoarthritis Guidelines: A Progressive Role for Topical Nonsteroidal Anti-inflammatory Drugs. Journal of Multidisciplinary Healthcare. 2013;6:133-137. https://doi.org/10.2147%2FJMDH.S35229
[9]. M. Qindeel, M.H. Ullah, Fakhar-ud-Din, N. Ahmed, A ur Rehman, Recent Trends, Challenges and Future Outlook of Transdermal Drug Delivery Systems for Rheumatoid Arthritis Therapy, J. Contr. 2020; 595–615, https://doi.org/10.1016/ j.jconrel.2020.09.016.
[10]. Anita C, Munira M, Mural Q, Shaily L. Topical Nanocarriers for Management of Rheumatoid Arthritis: A Review. Biomed Pharmacother. 2021;141:111880. doi:10.1016/j.biopha.2021.111880. Epub 2021 Jul 14. PMID: 34328101.
[11]. Sakeena MH, Elrashid SM, Muthanna FA, Ghassan ZA, Kanakal MM, Laila L, Munavvar AS, Azmin MN. Effect of Limonene on Permeation Enhancement of Ketoprofen in Palm Oil Esters Nanoemulsion. J Oleo Sci. 2010;59(7):395–400. doi:10.5650/jos.59.395. PMID: 20513974.
[12]. Shakeel F, Ramadan W, Ahmed MA. Investigation of True Nanoemulsions for Transdermal Potential of Indomethacin: Characterization, Rheological Characteristics, and Ex Vivo Skin Permeation Studies. J Drug Target. 2009;17(6):435–441. https://doi.org/10.1080/10611860902963021.
[13]. Shakeel F, Baboota S, Ahuja A, All J, Shafiq S. Skin Permeation Mechanism of Aceclofenac Using Novel Nanoemulsion Formulation. Pharmazie. 2008;63(8):580–4. PMID: 18771006.
[14]. Shakeel F, Baboota S, Ahuja A, Ali J, Shafiq S. Celecoxib Nanoemulsion for Transdermal Drug Delivery: Characterization and In Vitro Evaluation. J Dispersion Sci Technol. 2009;30(6):834–842. https://doi.org/10.1080/01932690802644012
[15]. Kima CS, Kawadab T, Kimc BS, Hanc IS, Choea SY, Kuratad T, et al. Capsaicin exhibits anti-inflammatory property by inhibiting IκB-α degradation in LPS-stimulated peritoneal macrophages. Cell Signal. 2003;15(3):299-306.
[16]. Seca S, Geada L, Cabrita AS. Topical Effects of Capsicum frutescens on Hand Pain in Patients with Rheumatoid Arthritis: A Case Report. J Tradit Med Clin Natur. 2017;6:207. https://doi.org/10.4172/2573-4555.1000207
[17]. Suardi M, Putra PP, Wahyunit N, Lucida H. Evaluation of Physicochemical and Antifungal Properties of Microemulsions of Lemongrass Oil (Cymbopogon citratus) and Clove Oil (Syzygium aromaticum). Trop J Nat Prod Res. [Internet]. [cited 2025 Jun 3]; Available from: https://www.tjnpr.org
[18]. Ordoñez Lozada MI, Maldonade IR, Rodrigues DB, Santos DS, Sanchez BAO, Souza PEN, Longo JP, Amaro GB, Oliveira LL. Physicochemical characterization and nano-emulsification of three species of pumpkin seed oils with focus on their physical stability. Food Chem. 2021;343:128512. https://doi.org/10.1016/j.foodchem.2020.128512
[19]. Elhoseny SM, Saleh NM, Meshali MM. Self-nanoemulsion intrigues the gold phytopharmaceutical chrysin: in vitro assessment and intrinsic analgesic effect. AAPS PharmSciTech. 2024;25:54. https://doi.org/10.1208/s12249-024-02767-0
[20]. Paliwal S, Kaur G, Arya R. Formulation and Characterization of Topical Nano Emulgel of Terbinafine. Universal Journal of Pharmaceutical Research. 2019;3(6):28–34. https://dx.doi.org/10.22270/ujpr.v3i6.223
[21]. Kadhim Drais H, Hussein AA. Formulation, characterization and evaluation of meloxicam nanoemulgel to be used topically. Iraqi J Pharm Sci. 2017;26(1):9-16. Available from: https://www.bijps.uobaghdad.edu.iq/index.php/bijps/article/view/681
[22]. Radhika PR, Guruprasad S. Nanoemulsion based emulgel formulation of lipophilic drug for topical delivery. Int J PharmTech Res. 2016;9(6):210-23. ISSN: 0974-4304. ISSN(Online): 2455-9563.
[23]. Preeti, Sambhakar S, Malik R, Bhatia S, Al Harrasi A, Rani C, Saharan R, Kumar S, Geeta, Sehrawat R. Nanoemulsion: an emerging novel technology for improving the bioavailability of drugs. Scientifica (Cairo). 2023;2023:6640103. https://doi.org/10.1155/2023/6640103. PMID: 37928749; PMCID: PMC1062549.
[24]. Subramanian P, Siddalingam R. Self-nanoemulsifying drug delivery systems of poorly soluble drug dutasteride: formulation and in-vitro characterization. J Appl Pharm Sci. 2017;7(4):11-22. https://doi.org/10.7324/JAPS.2017.70402
[25]. Afriwardi AA, Nazmi R, Dillasamola D, Badriyya E, Aldi Y. Anti-inflammatory Activity of Pegagan Embun (Hydrocotyle sibthorpioides Lam.) Plant Extract on Topical Application. Pharmacognosy Journal. 2020; 13(2):411–7. https://dx.doi.org/10.5530/pj.2021.13.52
[26]. Kementerian Kesehatan Republik Indonesia. Supplement I to the Indonesian Herbal Pharmacopoeia 2nd Edition. 2022; Jakarta: Kementerian Kesehatan
[27]. Hasani F, Pezeshki A, Hamishehkar H. Effect of surfactant and oil type on size droplets of beta-carotene-bearing nanoemulsions. Int J Curr Microbiol Appl Sci. 2015;4(9):146-55. ISSN: 2319-7706. Available from: https://www.ijcmas.com
[28]. Yadav V, Jadhav P, Kanase K, Bodhe A, Dombe S. Preparation and Evaluation of Microemulsion Containing Antihypertensive Drug. International Journal of Applied Pharmaceutics. 2018;10(5):138-146. https://doi.org/10.22159/ijap.2018v10i5.27415
[29]. Che Sulaiman IS, Basri M, Fard Masoumi HR, Ashari SE, Ismail M. Design and development of a nanoemulsion system containing extract of Clinacanthus nutans (L.) leaves for transdermal delivery system by D-optimal mixture design and evaluation of its physicochemical properties. RSC Adv. 2016;6(71):67378-88. https://doi.org/10.1039/C6RA12930G
[30]. Chuacharoen T, Prasongsuk S, Sabliov CM. Effect of Surfactant Concentrations On Physicochemical Properties And Functionality Of Curcumin Nanoemulsions Under Conditions Relevant To Commercial Utilization. Molecules. 2019;24(15):2744. https://doi.org/10.3390/molecules24152744
[31]. Atun S, Arianingrum R, Cahyaningsih L, Pratiwi FA, Kusumaningrum R, Khairuddean M. Formulation And Characterization Of Quercitrin Nanoemulsion Isolated From Dendropthoe falcata And Its Antioxidant Activity Test. Rasayan J Chem. 2020;13(3):1347–1356. https://doi.org/10.31788/RJC.2020.1335868
[32]. Iskandar B, Mei HC, Liu TW, Lin HM, Lee CK. Evaluating the effects of surfactant types on the properties and stability of oil-in-water Rhodiola rosea nanoemulsion. Colloids Surf B Biointerfaces. 2024;234:113692. https://doi.org/10.1016/j.colsurfb.2023.113692
[33]. Rajpoot K, Tekade RK. Microemulsion As Drug And Gene Delivery Vehicle: An Inside Story. In: Tekade Rk, Editor. Advances In Pharmaceutical Product Development And Research: Drug Delivery Systems. Cambridge: Academic Press; 2019. p. 455–520. https://doi.org/10.1016/B978-0-12-814487-9.00010-7
[34]. Jürgens L, Nichtl A, Werner U. Electron Density Imaging Of Protein Films On Gold-Particle Surfaces With Transmission Electron Microscopy. Cytometry. 1999;37(2):87–92. PMID: 10486520.
[35]. Badan Standarisasi Nasional. SNI 16-4380-1996: Produk Pembersih Wajah. Jakarta: Badan Standarisasi Nasional; 1996.
[36]. Hammell DC, Zhang LP, Ma F, Abshire SM, McIlwrath SL, Stinchcomb AL, Westlund KN. Transdermal Cannabidiol Reduces Inflammation And Pain-Related Behaviours In a Rat Model Of Arthritis. Eur J Pain. 2016;20(6):936–948. https://doi.org/10.1002/ejp.818
[37]. Okoro NK, Oseni BA, Okubanjo OO, Adegun AA, Ilomuanya MO. Development Of Diclofenac And Capsaicin Emulgel For The Management Of Inflammation In Rheumatoid Arthritis. Trop J Nat Prod Res. 2023;7(6):3246–52. https://www.tjnpr.org/index.php/tjnpr/article/view/1796