Determination of Photoprotective Capacity of Topical Gel Formulations Containing  Bioactive Compound Rutin and Evaluation of Physicochemical Stability: http://www.doi.org/10.26538/tjnpr/v7i9.12

Melta A. Nadia; Abdul K.  Zulkarnain; Teuku N. S.  Sulaiman

Authors

Melta A. Nadia Master in Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Sleman, Yogyakarta 55281, Indonesia
Abdul K. Zulkarnain Department of Pharmaceutics, Faculty of Pharmacy, Gadjah Mada University, Sekip Utara, Sleman, Yogyakarta 55281, Indonesia
Teuku N. S. Sulaiman Department of Pharmaceutics, Faculty of Pharmacy, Gadjah Mada University, Sekip Utara, Sleman, Yogyakarta 55281, Indonesia

Keywords:

sun protection factor, sunscreen, rutin, gel

Abstract

A series of skin damages are mediated by excessive exposure to ultraviolet B (UVB) radiation. Chemical UV filters can cause photodegradation and adverse effects on the skin. Rutin is a natural multifunctional nutraceutical that can prevent damage from sun radiation. This compound is found in fruits, vegetables, and grains. Previous studies have reported rutin as a good antioxidant and photoprotective agent in sunscreen formulations. This work focused on the development of a formulation and evaluation of the protective activity of rutin as a single compound in sunscreen preparations. The Design Expert software was used for formulation
optimization. Photoprotection testing was conducted in vitro by observing the parameters of Sun Protection Factor (SPF), percentage of erythema transmission, and pigmentation. Freeze-thaw cycling test and storage at room temperature were performed to evaluate the stability of the formulation. The optimum formula has good characteristics with a pH value of 6.207±0.013, viscosity of 76.5±0.1, spreadability of 10.82±0.440, and adhesiveness of 1.280±0.027. This sunscreen formulation provided a high level of protection with a sun protection factor (SPF) value of 38.11±0.082. The percentage of erythema and pigmentation transmission fell within the sunblock category. Although there were variations in the SPF values when rutin was formulated into the sunscreen, the overall quality of protection was not compromised. The physical and chemical properties of this sunscreen formulation remained stable after stability testing.

References

Ngoc, Tran, Moon, Chae, Park, Lee. Recent Trends of Sunscreen Cosmetic: An Update Review. Cosmetics. 2019 Nov 1;6(4):64.

de Oliveira CA, Peres DD, Rugno CM, Kojima M, Pinto CAS de O, Consiglieri VO, Kaneko TM, Rosado C, Mota J, Velasco MVR, Baby AR. Functional photostability and cutaneous compatibility of bioactive UVA sun care products. J Photochem Photobiol B. 2015 Jul;148:154–9.

Tomazelli LC, de Assis Ramos MM, Sauce R, Cândido TM, Sarruf FD, de Oliveira Pinto CAS, de Oliveira CA, Rosado C, Velasco MVR, Baby AR. SPF enhancement provided by rutin in a multifunctional sunscreen. Int J Pharm. 2018 Dec;552(1–2):401–6.

Chua LS. A review on plant-based rutin extraction methods and its pharmacological activities. J Ethnopharmacol. 2013 Dec;150(3):805–17.

Junker-Frohn LV, Lück M, Schmittgen S, Wensing J, Carraresi L, Thiele B, Groher T, Reimer JJ, Bröring S, Noga G, Jupke A, Schurr U, Usadel B, Wiese-Klinkenberg A, Wormit A. Tomato’s Green Gold: Bioeconomy Potential of Residual Tomato Leaf Biomass as a Novel Source for the

Secondary Metabolite Rutin. ACS Omega. 2019 Nov 19;4(21):19071–80.

Prasad R, Prasad SB. A review on the chemistry and biological properties of Rutin, a promising nutraceutical agent. Asian J Pharm Pharmacol. 2019 Jun;5(S1):1–20.

Enenebeaku UE, Duru CE, Okotcha EN, Ogidi OI, Mgbemena IC, Nwigwe HC, Enenebeaku CK. Phytochemical Analysis and Antioxidant Evaluation of Crude Extracts from the Roots, Stem and Leaves of Dictyandraarborescens (Welw.). Trop J Nat Prod Res. 2022 Feb 3;6(1):62–70.

Rasheed A, Shama SN, Mohanalakshmi S, Ravichandran V. Formulation, characterization and in vitro evaluation of herbal sunscreen lotion. Orient Pharm Exp Med. 2012 Dec;12(4):241–6.

Geoffrey K, Mwangi AN, Maru SM. Sunscreen products: Rationale for use, formulation development and regulatory considerations. Saudi Pharm J. 2019 Nov;27(7):1009–18.

Kajbafvala A, Salabat A. Microemulsion and microemulsion gel formulation for transdermal delivery of rutin: Optimization, in-vitro/ex-vivo evaluation and SPF determination. J Dispers Sci Technol. 2021 Feb 11;1–9.

Vu HTH, Hook SM, Siqueira SD, Müllertz A, Rades T, McDowell A. Are phytosomes a superior nanodelivery system for the antioxidant rutin? Int J Pharm. 2018 Sep;548(1):82–91.

Mascaraque C, Aranda C, Ocón B, Monte MJ, Suárez MD, Zarzuelo A, Marín JJG, Martínez-Augustin O, de Medina FS. Rutin has intestinal antiinflammatory effects in the CD4+ CD62L+ T cell transfer model of colitis. Pharmacol Res. 2014 Dec;90:48–57.

Pinzaru I, Chioibas R, Marcovici I, Coricovac D, Susan R, Predut D, Georgescu D, Dehelean C. Rutin Exerts Cytotoxic and Senescence-Inducing Properties in Human Melanoma Cells. Toxics. 2021 Sep 19;9(9):226.

Choi SJ, Lee SN, Kim K, Joo DH, Shin S, Lee J, Lee HK, Kim J, Kwon SB, Kim MJ, Ahn KJ, An IS, An S, Cha HJ. Biological effects of rutin on skin aging. Int J Mol Med. 2016 Jul;38(1):357–63.

Panasiak W, Wleklik M, Oraczewska A, Luczak M. Influence of flavonoids on combined experimental infections with EMC virus and Staphylococcus aureus in mice. Acta Microbiol Pol. 1989;38(2):185–8.

Oliveira CA de, Peres DD, Graziola F, Chacra NAB, Araújo GLB de, Flórido AC, Mota J, Rosado C, Velasco MVR, Rodrigues LM, Fernandes AS, Baby AR. Cutaneous biocompatible rutin-loaded gelatin-based nanoparticles increase the SPF of the association of UVA and UVB filters. Eur J Pharm Sci. 2016 Jan;81:1–9.

Peres DA, de Oliveira CA, da Costa MS, Tokunaga VK, Mota JP, Rosado C, Consiglieri VO, Kaneko TM, Velasco MVR, Baby AR. Rutin increases critical wavelength of systems containing a single UV filter and with good skin compatibility. Skin Res Technol. 2016 Aug;22(3):325–33.

Nabi SAA, Sheraz MA, Ahmed S, Mustaan N, Ahmad I. Pharmaceutical Gels: A Review. RADS-JPPS. 2016;4:40–4.

Vckn D, P B, M P, S T, Ran D, S S, C V. Deuschle VCKN. Rutin Release of Gel Formulations Containing Persea Americana Mill. Extract in Vertical Difusion System in Vitro. J Cosmetol. 2019;2–8.

Noval N, Rosyifa R, Annisa A. Effect of HPMC Concentration Variation as Gelling Agent on Physical Stability of Formulation Gel Ethanol Extract Bundung Plants (Actinuscirpus Grossus). In: Proceedings of the Proceedings of the First National Seminar Universitas Sari Mulia, NS-UNISM 2019, 23rd November 2019, Banjarmasin, South Kalimantan, Indonesia [Internet]. Banjarmasin, Indonesia: EAI; 2020 [cited 2022 Aug 10].

Available from: http://eudl.eu/doi/10.4108/eai.23-11-2019.2298326

Kamel R, Mostafa DM. Rutin nanostructured lipid cosmeceutical preparation with sun protective potential. J Photochem Photobiol B. 2015 Dec;153:59–66.

Kovalchuk NM, Dunn J, Davies J, Simmons MJH. Superspreading on Hydrophobic Substrates: Effect of Glycerol Additive. Colloids Interfaces. 2019 May 31;3(2):51.

Ermawati DE, Yugatama A, Wulandari W. Optimization of Olive Oil, Tween 80, and Propylene Glycol of Selfnanoemulsifying Drug Delivery System of Zinc Oxide by D-Optimal Method. J Pharm Sci Community. 2020 Dec 31;17(2):92–101.

Sheskey PJ, Cook WG, Cable CG, editors. Handbook of Pharmaceutical Excipients. 8th ed. London: Pharmaceutical Press; 2017.

Carrer V, Alonso C, Pont M, Zanuy M, Córdoba M, Espinosa S, Barba C, Oliver MA, Martí M, Coderch L. Effect of propylene glycol on the skin penetration of drugs. Arch Dermatol Res [Internet]. 2020 Jul [cited 2022 Oct 25];312(5). Available from: http://link.springer.com/10.1007/s00403-019-02017-5

Mohamad Zen NI, Abd Gani SS, Shamsudin R, Fard Masoumi HR. The Use of D-Optimal Mixture Design in Optimizing Development of Okara Tablet Formulation as a Dietary Supplement. Sci World J. 2015;2015:1–7.

Dutra EA, Oliveira DAG da C, Kedor-Hackmann ERM, Santoro MIRM. Determination of sun protection factor (SPF) of sunscreens by ultraviolet spectrophotometry. Rev Bras Ciênc Farm. 2004 Sep;40(3):381–5.

Dimitrovska Cvetkovska A, Manfredini S, Ziosi P, Molesini S, Dissette V, Magri I, Scapoli C, Carrieri A, Durini E, Vertuani S. Factors affecting SPF in vitro measurement and correlation with in vivo results. Int J Cosmet Sci. 2017;39(3):310–9.

Sudhahar V, Balasubramanian V. Sun production factor (SPF) determination of marketed sunscreen formulation by In-Vitro method using UV-VIS spectrophotometer. 2013;119–22.

Mansur J de S, Breder MNR, Mansur MC d’Ascençäo, Azulay RD. Determinaçäo do fator de proteçäo solar por espectrofotometria. Bras Dermatol. 1986;121–4.

Sayuti NA. Formulasi dan Uji Stabilitas Fisik Sediaan Gel Ekstrak Daun Ketepeng Cina (Cassia alata L.). J Kefarmasian Indones. 2015 Aug 28;5(2):74–80.

Cumpelik M. Analytical Procedures and Evaluation of Sunscreens. J Soc Cosmet Chem. 1972;333–44.

Balsam MS, Sagarin E. Cosmetics: Science and Technology. 2nd ed. Vols 1–3. New York: Interscience Publishers Inc; 1972.

Harmita. Petunjuk Pelaksanaan Validasi Metode dan Cara Perhitungannya. Maj Ilmu Kefarmasian. 2004 Dec;1(3):117–35.

Fiume MM, Heldreth B, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler D, Marks JG, Shank RC, Slaga TJ, Snyder PW, Andersen FA. Safety Assessment of Triethanolamine and Triethanolamine-Containing Ingredients as Used in Cosmetics. Int J Toxicol. 2013 May;32:59S-83S.

Proksch E. pH in nature, humans and skin. J Dermatol. 2018 Sep;45(9):2.

Hurler J, Engesland A, Poorahmary Kermany B, ŠkalkoBasnet N. Improved texture analysis for hydrogel characterization: Gel cohesiveness, adhesiveness, and hardness. J Appl Polym Sci. 2012 Jul 5;125(1):180–8.

Afianti HP, Murrukmihadi M. Pengaruh Variasi Kadar Gelling Agent Hpmc Terhadap Sifat Fisik dan Aktivitas Antibakteri Sediaan Gel Ekstrak Etanolik Daun Kemangi (Ocimum basilicum L. forma citratum Back.). 2015;11(2).

Islam MT, Rodríguez-Hornedo N, Ciotti S, Ackermann C. Rheological Characterization of Topical Carbomer Gels Neutralized to Different pH. Pharm Res. 2004 Jul;21(7):1192–9.

Swari Maharani NPD, Cahyani IM, Hanhadyanaputri ES. Optimization of Polyvinyl Alcohol (PVA) and Glycerin in Kolang Kaling Peel-Off Gel Mask Formula (Arenga pinnata.). J Food Pharm Sci. 2022 Dec 31;746–53.

Gunarti NS, Fikayuniar L. Formulasi dan Uji Aktivitas Gel Tabir Surya dari Ekstrak Buah Blackberry (Rubus Fruticosus) Secara In Vitro dengan Spektrofotometri UVVisibel. Kartika J Ilm Farm. 2020 Aug 25;7(2):68.

Jones DS, Woolfson AD, Brown AF. Textural, viscoelastic and mucoadhesive properties of pharmaceutical gels composed of cellulose olymers. Int J Pharm [Internet]. 1997 May 26 [cited 2022 Oct 17];151(2). Available from: https://linkinghub.elsevier.com/retrieve/pii/S037851739704

Patlolla VGR, Holbrook WP, Gizurarson S, Kristmundsdottir P. Evaluation of in vitro mucoadhesiveness and texture profile analysis of

doxycycline in situ hydrogels. Pharmazie [Internet]. 2020 Jan [cited 2022 Oct 17];(1). Available from: https://doi.org/10.1691/ph.2020.9122

Huang J, Peng S, Gu J, Chen G, Gao J, Zhang J, Hou L, Yang X, Jiang X, Guan L. Self-powered integrated system of a strain sensor and flexible all-solid-state supercapacitor by using a high performance ionic organohydrogel. Mater Horiz. 2020;7(8):2085–96.

Chen G, Hu O, Lu J, Gu J, Chen K, Huang J, Hou L, Jiang X. Highly flexible and adhesive poly(vinyl alcohol)/poly(acrylic amide-co-2-acrylamido-2-methylpropane sulfonic acid)/glycerin hydrogel electrolyte for stretchable and resumable supercapacitor. Chem Eng J. 2021 Dec;425:131505.

Osterwalder U, Herzog B. Sun protection factors: world wide confusion. Br J Dermatol. 2009 Nov;161:13–24.

Choi KS, Kundu JK, Chun KS, Na HK, Surh YJ. Rutin inhibits UVB radiation-induced expression of COX-2 and iNOS in hairless mouse skin: p38 MAP kinase and JNK as potential targets. Arch Biochem Biophys. 2014 Oct;559:38–45.

Satari A, Ghasemi S, Habtemariam S, Asgharian S, Lorigooini Z. Rutin: A Flavonoid as an Effective Sensitizer for Anticancer Therapy; Insights into Multifaceted Mechanisms and Applicability for Combination Therapy. Malfa G, editor. Evid Based Complement Alternat Med. 2021 Aug 23;2021:1–10.

Dunaway S, Odin R, Zhou L, Ji L, Zhang Y, Kadekaro AL. Natural Antioxidants: Multiple Mechanisms to Protect Skin From Solar Radiation. Front Pharmacol. 2018 Apr 24;9:392.

Mohania D, Chandel S, Kumar P, Verma V, Digvijay K, Tripathi D, Choudhury K, Mitten SK, Shah D. Ultraviolet Radiations: Skin Defense-Damage Mechanism. In: Ahmad SI, editor. Ultraviolet Light in Human Health, Diseases and Environment [Internet]. Cham: Springer International

Publishing; 2017 [cited 2022 Aug 29]. p. 71–87. (Advances in Experimental Medicine and Biology; vol. 996). Available from: http://link.springer.com/10.1007/978-3-319-56017-5_7

Gęgotek A, Rybałtowska-Kawałko P, Skrzydlewska E. Rutin as a Mediator of Lipid Metabolism and Cellular Signaling Pathways Interactions in Fibroblasts Altered by UVA and UVB Radiation. Oxid Med Cell Longev. 2017;2017:1–20.

Boo YC. Emerging Strategies to Protect the Skin from Ultraviolet Rays Using Plant-Derived Materials. Antioxidants. 2020 Jul 18;9(7):637.

Pivec, Kargl, Maver, Bračič, Elschner, Ţagar, Gradišnik, Kleinschek. Chemical Structure–Antioxidant Activity Relationship of Water–Based Enzymatic Polymerized Rutin and Its Wound Healing Potential. Polymers. 2019 Sep 26;11(10):1566.

Tsabitah AF, Zulkarnain AK, Wahyuningsih MSH, Nugrahaningsih DAA. Optimasi Carbomer, Propilen Glikol, dan Trietanolamin Dalam Formulasi Sediaan Gel Ekstrak Etanol Daun Kembang Bulan (Tithonia diversifolia). Maj Farm. 2020 Jun 23;16(2):115.

Rowe RC, Sheskey PJ, Quinn ME. Handbook of pharmaceutical excipients. 6th ed. London: Pharmaceutical press; 2009.

Vincentini FTMC, Georgetti SR, Jabor JR, Bentley MVLB, Fonseca MJV. Photostability of Quercetin under Exposure to UV irradiation. Lat Am J Pharm. 2007;26(1):119–24.

Kozlowska J, Pauter K, Sionkowska A. Carrageenan-based hydrogels: Effect of sorbitol and glycerin on the stability, swelling and mechanical properties. Polym Test [Internet]. 2018 May [cited 2022 Oct 25];67. Available from: https://linkinghub.elsevier.com/retrieve/pii/S014294181731

Larrea-Wachtendorff D, Di Nobile G, Ferrari G. Effects of processing conditions and glycerol concentration on rheological and texture properties of starch-based hydrogels produced by high pressure processing (HPP). Int J Biol Macromol [Internet]. 2020 Sep [cited 2022 Oct 25];159. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0141813020332724

Jerzykiewicz M, Cwielag I, Jerzykiewicz W. The antioxidant and anticorrosive properties of crude glycerol fraction from biodiesel production. J Chem Technol Biotechnol. 2009 Aug;84(8):1196–201.