Formulation and evaluation of Self-Nanoemulsifying Drug Delivery System (SNEDDS) Loaded with Usnic Acid for Topical Application

Main Article Content

Deni Noviza
Lili Fitriani
Nurul Husna
Sjaikhurrizal El Muttadien

Abstract

Usnic acid, a secondary metabolite derived from Usnea sp., exhibits diverse pharmacological activities; however, its therapeutic utility is constrained by poor aqueous solubility and risk of hepatotoxicity upon oral administration. To overcome these limitations, this study aimed to develop a self-nanoemulsifying drug delivery system (SNEDDS) of usnic acid tailored for topical application. The formulation was optimized via a pseudoternary phase diagram and characterized using a particle size analyzer (PSA) and transmission electron microscopy (TEM). The optimized SNEDDS—comprising grapeseed oil, Cremophor RH 40, and polyethylene glycol 400—exhibited rapid emulsification (0.87 ± 0.05 s) and high transmittance (99.12 ± 0.34%). PSA analysis revealed a globule size of 132.45 ± 4.21 nm, a polydispersity index (PDI) of 0.32 ± 0.02, and a zeta potential of −34.76 ± 1.15 mV, aligning with TEM observations that confirmed a spherical morphology. This optimized system was subsequently incorporated into a Carbopol Ultrez 30 hydrogel, yielding a homogeneous formulation with a pH of 5.86 ± 0.12 and a spreadability of 5.74 ± 0.28 cm. Upon incorporation into the gel framework, the SNEDDS maintained favorable characteristics, exhibiting a globule size of 148.67 ± 5.02 nm nm, a PDI of 0.36 ± 0.03, and a zeta potential of 31.42 ± 1.27 mV. Finally, in vitro release studies demonstrated that the SNEDDS hydrogel achieved an approximate two-fold increase in usnic acid release over 24 h compared to a conventional hydrogel, highlighting its potential as an effective topical delivery system

Article Details

How to Cite
Noviza, D., Fitriani, L., Husna, N., & Muttadien, S. E. (2026). Formulation and evaluation of Self-Nanoemulsifying Drug Delivery System (SNEDDS) Loaded with Usnic Acid for Topical Application. Jurnal Sains Farmasi & Klinis, 13(02), 203–213. https://doi.org/10.25077/jsfk.13.02.203-213.2026
Section
Research Articles

References

[1]. Wang H, Xuan M, Huang C, Wang C. Advances in Research on Bioactivity, Toxicity, Metabolism, and Pharmacokinetics of Usnic Acid In Vitro and In Vivo. Molecules. 2022;27(21):1–22. https://doi.org/10.3390/molecules27217469

[2]. Croce N, Pitaro M, Gallo V, Antonini G. Toxicity of Usnic Acid: A Narrative Review. J Toxicol. 2022;2022. https://doi.org/10.1155/2022/8244340

[3]. Botros SR, Hussein AK, Mansour HF. A Novel Nanoemulsion Intermediate Gel as a Promising Approach for Delivery of Itraconazole: Design, In Vitro and Ex Vivo Appraisal. AAPS PharmSciTech. 2020;21(7):12–4. https://doi.org/10.1208/s12249-020-01830-w

[4]. Lane ME. Skin penetration enhancers. Int J Pharm. 2013;447(1–2):12–21. https://doi.org/10.1016/j.ijpharm.2013.02.040

[5]. Lalatsa A, Statts L, Adriana de Jesus J, Adewusi O, Auxiliadora Dea-Ayuela M, Bolas-Fernandez F, et al. Topical buparvaquone nano-enabled hydrogels for cutaneous leishmaniasis. Int J Pharm. 2020;588(July):119734. https://doi.org/10.1016/j.ijpharm.2020.119734

[6]. Ponto T, Latter G, Luna G, Leite-Silva VR, Wright A, Benson HAE. Novel self-nano-emulsifying drug delivery systems containing astaxanthin for topical skin delivery. Pharmaceutics. 2021;13(5). https://doi.org/10.3390/pharmaceutics13050649

[7]. Frei G, Haimhoffer Á, Csapó E, Bodnár K, Vasvári G, Nemes D, et al. In Vitro and In Vivo Efficacy of Topical Dosage Forms Containing Self-Nanoemulsifying Drug Delivery System Loaded with Curcumin. Pharmaceutics. 2023;15(8). https://doi.org/10.3390/pharmaceutics15082054

[8]. Nasr A, Gardouh A, Ghorab M. Novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of olmesartan medoxomil: Design, formulation, pharmacokinetic and bioavailability evaluation. Pharmaceutics. 2016;8(3). https://doi.org/10.3390/pharmaceutics8030020

[9]. International Council For Harmonisation (ICH) Of Technical Requirements For Pharmaceuticals For Human Use. Validation of Analytical Procedures Q2(R2) [Internet]. 2022 [cited 2022 Dec 3]. Available from: https://www.ich.org/. 2022;2(March).

[10]. Alfaraj R, Hababah S, Eltayb EK, Alqahtani FY, Aleanizy FS. Isotretinoin self-nano-emulsifying drug delivery system: Preparation, optimization and antibacterial evaluation. Saudi Pharm J. 2024;32(6):102063. https://doi.org/10.1016/j.jsps.2024.102063

[11]. Ashfaq M, Shah S, Rasul A, Hanif M, Khan HU, Khames A, et al. Enhancement of the Solubility and Bioavailability of Pitavastatin through a Self-Nanoemulsifying Drug Delivery System (SNEDDS). Pharmaceutics. 2022;14(3). https://doi.org/10.3390/pharmaceutics14030482

[12]. Suhery WN, Sumirtapura YC, Pamudji JS, Mudhakir D. Development and characterization of self-nanoemulsifying drug delivery system (Snedds) formulation for enhancing dissolution of fenofibric acid. J Res Pharm. 2020;24(5):738–47. https://doi.org/10.35333/jrp.2020.227

[13]. Ahmad N, Ahmad R, Al-Qudaihi A, Alaseel SE, Fita IZ, Khalid MS, et al. A novel self-nanoemulsifying drug delivery system for curcumin used in the treatment of wound healing and inflammation. Biotech. 2019;9(10):1–20. https://doi.org/10.1007/s13205-019-1885-3

[14]. van Staden D, du Plessis J, Viljoen J. Development of a self-emulsifying drug delivery system for optimized topical delivery of clofazimine. Pharmaceutics. 2020;12(6):1–24. https://doi.org/10.3390/pharmaceutics12060523

[15]. Morakul B, Teeranachaideekul V, Limwikrant W, Junyaprasert VB. Dissolution and antioxidant potential of apigenin self nanoemulsifying drug delivery system (SNEDDS) for oral delivery. Sci Rep. 2024;14(1):1–13. https://doi.org/10.1038/s41598-024-59617-z

[16]. Rahayu YC, Setiawatie EM, Rahayu RP, Ulfa NMAS. Original Article Formulation and In Vivo Evaluation of Nanoemulgel-Containing Cocoa Pod Husk ( Theobroma Cacao L .) Extract As Topical Oral Preparation. 2024;16(5).

[17]. Fitriani L, Afifah, Ismed F, Bakhtiar A. Hydrogel formulation of usnic acid and antibacterial activity test against propionibacterium acne. Sci Pharm. 2019;87(1). https://doi.org/10.3390/scipharm87010001

[18]. Sethi A, Ahmad M, Huma T, Khalid I, Ahmad I. Evaluation of Low Molecular Weight Cross Linked Chitosan Nanoparticles, to Enhance the Bioavailability of 5-Flourouracil. Dose-Response. 2021;19(2):1–12. https://doi.org/10.1177/15593258211025353

[19]. Verma R, Kaushik A, Almeer R, Habibur Rahman M, Abdel-Daim MM, Kaushik D. Improved pharmacodynamic potential of rosuvastatin by self-nanoemulsifying drug delivery system: An in vitro and in vivo evaluation. Int J Nanomedicine. 2021;16:905–24. https://doi.org/10.2147/IJN.S287665

[20]. Lu L, Yang P, Chen T, Shen Y, Yao Q, Yan J. Changes in biological activities after olive oil, pomegranate seed oil, and grape seed oil were formulated into self-nanoemulsifying systems. J Oleo Sci. 2020;69(2):161–6. https://doi.org/10.5650/jos.ess19255

[21]. Rowe RC, J SP, Quinn ME. Handbook of Pharmaceutical Excipients Sixth Edition. Pharmaceutical Press; 2009.

[22]. Dehghani M, Zahir-Jouzdani F, Shahbaz S, Andarzbakhsh K, Dinarvand S, Fathian Nasab MH, et al. Triamcinolone-loaded self nano-emulsifying drug delivery systems for ocular use: An alternative to invasive ocular surgeries and injections. Int J Pharm. 2024;653(July 2023):123840. https://doi.org/10.1016/j.ijpharm.2024.123840

[23]. Noviza D, Rahim NAA, Hamid KA, Julianto T. Design and Development of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) Loaded with Xanthorrhizol. Malaysian J Med Heal Sci Supp 7. 2023;19(June 2023):24–5.

[24]. Rompicherla NC, Joshi P, Shetty A, Sudhakar K, Amin HIM, Mishra Y, et al. Design, Formulation, and Evaluation of Aloe vera Gel-Based Capsaicin Transemulgel for Osteoarthritis. Pharmaceutics. 2022;14(9):1–18. https://doi.org/10.3390/pharmaceutics14091812

[25]. Al Haushey L. Study of different factors affecting spreadability and release of Ibuprofen from carbopol gels using screening design methodology. Acta Pharm Sci. 2024;62(2):480–96. https://doi.org/10.23893/1307-2080.APS6230

[26]. Arora R, Aggarwal G, Harikumar SL, Kaur K. Nanoemulsion Based Hydrogel for Enhanced Transdermal Delivery of Ketoprofen. Adv Pharm. 2014;2014:1–12. https://doi.org/10.1155/2014/468456

[27]. Vikash B, Shashi, Pandey NK, Kumar B, Wadhwa S, Goutam U, et al. Formulation and evaluation of ocular self-nanoemulsifying drug delivery system of brimonidine tartrate. J Drug Deliv Sci Technol. 2023;81(September 2022):104226. https://doi.org/10.1016/j.jddst.2023.104226

[28]. Jana S, Manna S, Nayak AK, Sen KK, Basu SK. Carbopol gel containing chitosan-egg albumin nanoparticles for transdermal aceclofenac delivery. Colloids Surfaces B Biointerfaces. 2014;114:36–44. https://doi.org/10.1016/j.colsurfb.2013.09.045

[29]. Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm - Drug Res. 2010;67(3):217–23.