DEVELOPMENT AND CHARACTERIZATION OF NON-PROPELLANT FOAM INCORPORATED ACYCLOVIR FOR TREATMENT OF HERPES INFECTION
DOI:
https://doi.org/10.22159/ijap.2026v18i2.56156Keywords:
Non-propellent foam, Acyclovir, Nanoemulsions, Skin irritation, Topical formulationAbstract
Objective: Herpes simplex virus (HSV) belongs to the herpes viridae family and primarily spreads through skin-to-skin contact. The study aimed to formulate topical anti-herpes non-propellant foam (NPF) incorporating acyclovir, offering a convenient alternative to conventional formulations. NPF is an optically transparent, thermodynamically stable, and light in consistency and evenly spreadable, thereby enhancing the permeation and poor permeability of acyclovir.
Methods: The acyclovir nanoemulsion was formulated by the emulsification method and dispensed through a container, which, upon actuation, produced the foam. The NPF was characterized by globule size analysis, pH, viscosity, and foaming performances. The NPF was evaluated for the drug permeation ex vivo excised skin, and deposition, while cytocompatibility was determined in vitro in human keratinocytes, respectively.
Results: The nanoemulsion had a globule size, pH, and polydispersity(PDI) of about 68.00 to 110.00 nm, pH of ~6.30 and a PDI of<0.200. The nanoemulsion viscosity was (⁓0.90 mPa. s, Spindle TSP-2, 20 rpm at 20 °C,), indicating the feasibility of expulsion from the container. Once actuated, the foam stability was 33.33% in 3 min, the expansion time was 100 sec, and density was 0.28g/ml, with a measured bubble size of 90.00 to 200.00 nm. The drug permeation of acyclovir was 411.147 per cm2 (µg/ml) with a flux rate of 0.89µg/cm2/h, and a permeability coefficient of 0.1789 in ex vivo studies with drug deposition in the skin up to ~78%. In addition, cytocompatibility studies proved acyclovir NPF to be safe.
Conclusion: The work suggests that NPF to be a new promising dosage form for topical application. The formulation when applied to the skin, instantly disappeared with no residue and was able to cover large body surfaces, presenting a no-touch application.
References
1. Looker KJ, Magaret AS, Turner KM, Vickerman P, Gottlieb SL, Newman LM. Global estimates of prevalent and incident herpes simplex virus type 2 infections in 2012. PLOS One. 2015;10(1):e114989. doi: 10.1371/journal.pone.0114989, PMID 25608026.
2. James C, Harfouche M, Welton NJ, Turner KM, Abu-Raddad LJ, Gottlieb SL. Herpes simplex virus: global infection prevalence and incidence estimates, 2016. Bull World Health Organ. 2020;98(5):315-29. doi: 10.2471/BLT.19.237149, PMID 32514197.
3. Esser M. Ueber eine kleine epidemie von pustulosis acuta. Ann Paediatr. 1941;157:156-61.
4. De Clercq E, Field HJ. Antiviral prodrugs the development of successful prodrug strategies for antiviral chemotherapy. Br J Pharmacol. 2006;147(1):1-11. doi: 10.1038/sj.bjp.0706446, PMID 16284630.
5. Nair AB. Quantification of uptake and clearance of acyclovir in skin layers. Antivir Ther. 2016;21(1):17-25. doi: 10.3851/IMP2970, PMID 26046929.
6. Zigrayova D, Mikusova V, Mikus P. Advances in antiviral delivery systems and chitosan‑based polymeric and nanoparticulate antivirals and antiviral carriers. Viruses. 2023;15(3):647. doi: 10.3390/v15030647.
7. Gnann JW, Barton NH, Whitley RJ. Acyclovir: mechanism of action pharmacokinetics safety and clinical applications. Pharmacotherapy. 1983;3(5):275-83. doi: 10.1002/j.1875-9114.1983.tb03274.x, PMID 6359082.
8. Eita AS, Makky AM, Anter A, Khalil IA. Atorvastatin-loaded emulsomes foam as a topical antifungal formulation. Int J Pharm X. 2022;4(4):100140. doi: 10.1016/j.ijpx.2022.100140, PMID 36465276.
9. Arzhavitina A, Steckel H. Foams for pharmaceutical and cosmetic application. Int J Pharm. 2010;394(1-2):1-17. doi: 10.1016/j.ijpharm.2010.04.028, PMID 20434532.
10. Kurowska A, Ghate V, Kodoth A, Shah A, Shah A, Vishalakshi B. Non-propellant foams of green nano-silver and sulfadiazine: development and in vivo evaluation for burn wounds. Pharm Res. 2019;36(8):122. doi: 10.1007/s11095-019-2658-8, PMID 31218556.
11. Baghel S, Nair VS, Pirani A, Sravani AB, Bhemisetty B, Ananthamurthy K. Luliconazole-loaded nanostructured lipid carriers for topical treatment of superficial Tinea infections. Dermatol Ther. 2020;33(6):e13959. doi: 10.1111/dth.13959, PMID 32618400.
12. Kumar S, Wadhwa K, Pahwa R, Ali J, Baboota S. Screening of surfactant mixture ratio for preparation of oil-in-water nanoemulsion: a technical note. J Appl Pharm Sci. 2024;14(10):121-7. doi: 10.7324/JAPS.2024.180648.
13. Mirtic J, Papathanasiou F, Temova Rakusa Z, Gosenca Matjaz M, Roskar R, Kristl J. Development of medicated foams that combine incompatible hydrophilic and lipophilic drugs for psoriasis treatment. Int J Pharm. 2017;524(1-2):65-76. doi: 10.1016/j.ijpharm.2017.03.061, PMID 28359820.
14. Bibi S, Kaur R, Henriksen Lacey M, McNeil SE, Wilkhu J, Lattmann E. Microscopy imaging of liposomes: From cover slips to environmental SEM. Int J Pharm. 2011;417(1):138-50. doi: 10.1016/j.ijpharm.2010.12.021.
15. Asghar Z, Jamshaid T, Sajid-ur-rehman M, Jamshaid U, Gad HA. Novel Transethosomal gel containing miconazole nitrate; development, characterization and enhanced antifungal activity. Pharmaceutics. 2023;15(11):2537. doi: 10.3390/pharmaceutics15112537, PMID 38004517.
16. Khattab A, Shalaby S. Optimized ciclopirox-based eudragit RLPO nail lacquer: effect of endopeptidase enzyme as permeation enhancer on transungual drug delivery and efficiency against onychomycosis. AAPS PharmSciTech. 2018;19(3):1048-60. doi: 10.1208/s12249-017-0917-8, PMID 29138987.
17. Kaur M, Singh K, Jain SK. Luliconazole vesicular-based gel formulations for its enhanced topical delivery. J Liposome Res. 2020;30(4):388-406. doi: 10.1080/08982104.2019.1682602, PMID 31631734.
18. Plumb JA. Cell sensitivity assays: clonogenic assay. Methods Mol Med. 2004;88:159-64. doi: 10.1385/1-59259-406-9:159, PMID 14634226.
19. Vedha Hari BN, Narayanan N, Dhevedaran K. Efavirenz-eudragit E-100 nanoparticle-loaded aerosol foam for sustained release: in vitro and ex-vivo evaluation. Chemical Papers. 2015;69(2):358-67. doi: 10.1515/chempap-2015-0005.
20. Schmidt RF, Prause A, Prevost S, Doutch J, Gradzielski M. Phase behavior and structure of a biocompatible microemulsion based on Tween 20, 2-ethylhexylglycerine and isopropyl palmitate in water. Colloid Polym Sci. 2023;301(7):753-62. doi: 10.1007/s00396-023-05119-9.
21. Akram S, Anton N, Omran Z, Vandamme T. Water-in-oil nano-emulsions prepared by spontaneous emulsification: new insights on the formulation process. Pharmaceutics. 2021;13(7):1030. doi: 10.3390/pharmaceutics13071030, PMID 34371723.
22. Farkas D, Kallai Szabo N, Saradi Kesztyus A, Lengyel M, Magramane S, Kiss E. Investigation of propellant-free aqueous foams as pharmaceutical carrier systems. Pharm Dev Technol. 2021;26(3):253-61. doi: 10.1080/10837450.2020.1863426, PMID 33307920.
23. Souto EB, Cano A, Martins Gomes C, Coutinho TE, Zielinska A, Silva AM. Microemulsions and nanoemulsions in skin drug delivery. Bioengineering (Basel). 2022;9(4):158. doi: 10.3390/bioengineering9040158, PMID 35447718.
24. Chen L, Annaji M, Kurapati S, Ravis WR, Jayachandra Babu R. Microemulsion and microporation effects on the genistein permeation across dermatomed human skin. AAPS PharmSciTech. 2018;19(8):3481-9. doi: 10.1208/s12249-018-1150-9, PMID 30140994.
25. Elshall AA, Ghoneim AM, Abdel Mageed HM, Osman R, Shaker DS. Ex vivo permeation parameters and skin deposition of melatonin-loaded microemulsion for treatment of alopecia. Futur J Pharm Sci. 2022;8(1):4-10. doi: 10.1186/s43094-022-00418-4.
26. Pa D, Phuvisaa B, Kiruthika S, Mohamed A, Abirami D, Gokul K. Design and optimization of acyclovir-loaded solid lipid nanoparticles: a sustained release approach. Int J Appl Pharm. 2025;17(1):355-64. doi: 10.22159/ijap.2025v17i1.51877.
Published
How to Cite
Issue
Section
Copyright (c) 2026 PRAJITHA BIJU, VIVEK GHATE, SHAILA LEWIS, ASHWINI PRABHU

This work is licensed under a Creative Commons Attribution 4.0 International License.