Skip to main content

In Vitro Evaluation of a Foamable Microemulsion Towards an Improved Topical Delivery of Diclofenac Sodium


Topical microemulsion (ME) might provide a novel and advanced transdermal delivery system due to the enhances of drug solubility and permeability across the stratum corneum. Foams are topical delivery systems that have excellent patient compliance, acceptability, and preference. Therefore, this study aimed to investigate a foamable microemulsion as an alternative topical and transdermal dosage form for diclofenac sodium (DS). The physicochemical properties (optical clarity, percentage transmittance, homogeneity, consistency of formulation, particle size, zeta potential, conductivity, viscosity, and morphology, etc.) of the DS-loaded ME were investigated. The foam stability of both drug-free ME and DS-loaded ME was measured. The foam quality was evaluated, and the chemical stability over 90 days was determined. Franz diffusion cells were employed to assess the in vitro drug release of a foamed DS-loaded ME and compared with a commercial topical product. A foamable and stable DS-loaded ME that maintained small particle sizes and constant zeta potential and was transparent and translucent in appearance after 90 days was successfully produced. The foam of the DS-loaded ME was physically more stable compared to the drug-free foam. The foam had an increased drug release rate compared to the commercial product. The foamable DS-loaded ME has a great potential to enhance the transdermal delivery of DS after topical administration. Foamed DS-loaded ME is a promising alternative to the current topical formulation of DS.

Graphical Abstract

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5


  1. Komatsu T, Sakurada T. Comparison of the efficacy and skin permeability of topical NSAID preparations used in Europe. Eur J Pharm Sci. 2012;47(5):890–5.

    CAS  Article  Google Scholar 

  2. Balasubramanian R, Sughir AA, Damodar G. Oleogel: a promising base for transdermal formulations. Asian J Pharm. 2012;6(1):1–9.

    Article  Google Scholar 

  3. Singla V, Saini S, Joshi B, Rana AC. Emulgel: a new platform for topical drug delivery. Int J Pharma Bio Sci. 2012;3(1):485–98.

    CAS  Google Scholar 

  4. George S, Roy A. Topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: a short review. J Pain Manag. 2014;7(5):257–60.

    Google Scholar 

  5. Banning M. Topical diclofenac: clinical effectiveness and current uses in osteoarthritis of the knee and soft tissue injuries. Expert Opin Pharmacother. 2008;9(16):2921–9.

    CAS  Article  Google Scholar 

  6. Zur E. Topical treatment of neuropathic pain using compounded medications. Clin J Pain. 2014;30(1):73–91.

    Article  Google Scholar 

  7. FDA. Voltaren® Gel (diclofenac sodium topical gel), For topical use only. 2009. Accessed on 12 May 2021.

  8. Hajjar B, Zier K-I, Khalid N, Azarmi S, Löbenberg R. Evaluation of a microemulsion-based gel formulation for topical drug delivery of diclofenac sodium. J Pharm Investig. 2018;48(3):351–62.

    CAS  Article  Google Scholar 

  9. Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev. 2000;45(1):89–121.

    CAS  Article  Google Scholar 

  10. Nastiti CMRR, Ponto T, Abd E, Grice JE, Benson HAE, Roberts MS. Topical nano and microemulsions for skin delivery. Pharmaceutics. 2017;9(4):37.

    Article  Google Scholar 

  11. Sharadha M, Gowda DV, Vishal Gupta N, Akhila AR. An overview on topical drug delivery system – updated review. Int J Res Pharm Sci. 2020;11(1):368–85.

    CAS  Article  Google Scholar 

  12. Purdon CH, Haigh JM, Surber C, Smith EW. Foam drug delivery in dermatology. Am J Drug Deliv. 2003;1(1):71–5.

    Article  Google Scholar 

  13. Zhao Y, Jones SA, Brown MB. Dynamic foams in topical drug delivery. J Pharm Pharmacol. 2010;62(6):678–84.

    CAS  Article  Google Scholar 

  14. Tamarkin D, Friedman D, Shemer A. Emollient foam in topical drug delivery. Expert Opin Drug Deliv. 2006;3(6):799–807.

    CAS  Article  Google Scholar 

  15. Parsa M, Trybala A, Malik DJ, Starov V. Foam in pharmaceutical and medical applications. Curr Opin Colloid Interface Sci. 2019;44:153–67.

    CAS  Article  Google Scholar 

  16. Zhao Y, Brown MB, Jones SA. Pharmaceutical foams: are they the answer to the dilemma of topical nanoparticles? Nanomedicine: NBM. 2010;6(2):227–36.

    CAS  Article  Google Scholar 

  17. Barkin RL. Topical nonsteroidal anti-inflammatory drugs: the importance of drug, delivery, and therapeutic outcome. Am J Ther. 2015;22(5):388–407.

    Article  Google Scholar 

  18. Housman TS, Mellen BG, Rapp SR, Fleischer AB Jr, Feldman SR. Patients with psoriasis prefer solution and foam vehicles: a quantitative assessment of vehicle preference. Cutis. 2002;70(6):327–32.

    PubMed  Google Scholar 

  19. Gottlieb AB, Ford RO, Spellman MC. The efficacy and tolerability of clobetasol propionate foam 0.05% in the treatment of mild to moderate plaque-type psoriasis of nonscalp regions. J Cutan Med Surg. 2003;7(3):185–92.

    Article  Google Scholar 

  20. U.S Food and Drug Administration. VERDESO (desonide) foam, for topical use [Internet]. Orange Book Approved Drug Prod. with Ther. Equiv. Eval. 2019 [cited 2022 Feb 2]. Available from: Accessed 15 Mar 2022

  21. Arzhavitina A, Steckel H. Foams for pharmaceutical and cosmetic application. Int J Pharm. 2010;394(1–2):1–17.

    CAS  Article  Google Scholar 

  22. Griffin W. Classification of surface-active agents by “HLB”. J Soc Cosmet Chem. 1949;1(5):311–26.

    Google Scholar 

  23. Bou-Chacra N, Melo KJC, Morales IAC, Stippler ES, Kesisoglou F, Yazdanian M, et al. Evolution of choice of solubility and dissolution media after two decades of biopharmaceutical classification system. AAPS J. 2017;19(4):989–1001.

    CAS  Article  Google Scholar 

  24. Kealy T, Abram A, Hunt B, Buchta R. The rheological properties of pharmaceutical foam: implications for use. Int J Pharm. 2008;355(1–2):67–80.

    CAS  Article  Google Scholar 

  25. Gennari CGM, Selmin F, Minghetti P, Cilurzo F. Medicated foams and film forming dosage forms as tools to improve the thermodynamic activity of drugs to be administered through the skin. Curr Drug Deliv. 2019;16(5):461–71.

    CAS  Article  Google Scholar 

  26. Council of Europe. Medicated Foam. Eur Pharmacopoeia. 10th ed. Strasbourg: Council of Europe; 2008. p. 911.

    Google Scholar 

  27. Mauer L. PROTEIN | Heat Treatment for Food Proteins. In: Caballero B, editor. Encycl Food Sci Nutr. 2nd ed. Cambridge: Academic Press; 2003. p. 4868–72.

    Chapter  Google Scholar 

  28. Zuo J, Gao Y, Bou-Chacra N, Löbenberg R. Evaluation of the DDSolver software applications. Biomed Res Int. 2014;2014:204925.

    PubMed  PubMed Central  Google Scholar 

  29. Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DDSolver: An add-in program for modeling and comparison of drug dissolution profiles. AAPS J. 2010;12(3):263–71.

    Article  Google Scholar 

  30. Soleymani SM, Salimi A. Enhancement of dermal delivery of finasteride using microemulsion systems. Adv Pharm Bull. 2019;9(4):584–92.

    CAS  Article  Google Scholar 

  31. Salager J-L. Emulsion properties and related know-how to attain them. In: Nielloud F, Marti-Mestres G, editors. Pharm Emuls Suspens. 2nd ed. New York: Marcel Dekker, Inc; 2000. p. 73–125.

    Chapter  Google Scholar 

  32. Froelich A, Osmałek T, Kunstman P, Jadach B, Brzostowska M, Białas W. Design and study of poloxamer-based microemulsion gels with naproxen. Colloids Surf A Physicochem Eng Asp. 2019;562:101–12.

    CAS  Article  Google Scholar 

  33. Petkova R, Tcholakova S, Denkov ND. Foaming and foam stability for mixed polymer-surfactant solutions: effects of surfactant type and polymer charge. Langmuir. 2012;28(11):4996–5009.

    CAS  Article  Google Scholar 

  34. Chang Q. Emulsion, foam, and gel. In Colloid interface Chem Water Qual Control. Cambridge: Academic Press; 2016. p. 227–45.

  35. Jong SYC, Nguyen QP. Effect of microemulsion on foam stability. Appl Nanosci. 2018;8(3):231–9.

    CAS  Article  Google Scholar 

  36. Wilson A. Experimental techniques for the characterization of foams. In: Prud’homme R, Khan S, editors. Foam Theory, Meas Appl. 1st ed. New York: CRC Press; 1995. p. 243–74.

    Google Scholar 

  37. Markworth AJ. Comments on foam stability, Ostwald ripening, and grain growth. J Colloid Interface Sci. 1985;107(2):569–71.

    CAS  Article  Google Scholar 

  38. Stone HA, Koehler SA, Hilgenfeldt S, Durand M. Perspectives on foam drainage and the influence of interfacial rheology. J Phys Condens Matter. 2003;15:283–90.

    Article  Google Scholar 

  39. Da Silva JA, De Santana DP, Bedor DGC, Borba VFDC, Lira AAM, Egito EST Do. In vitro release and permeation of a diclofenac diethylamine from microemulsion gel-like. Quim Nova. 2009;32(6):1389–93.

  40. Banh HL, Cave A. Determination of efficacy and toxicity of diclofenac microemulsion formulation for musculoskeletal pain: an observational study. BMC Res Notes. 2020;13(1):285.

    CAS  Article  Google Scholar 

Download references


The authors acknowledge the support of the Drug Development and Innovation Centre at the University of Alberta and Applied Pharmaceutical Innovation.


Funding support was provided by Taibah University (Madinah, Saudi Arabia), Mitacs Accelerate (IT24899, Mitacs, Canada), and the Alberta Innovates Graduate Student Scholarship (Canada).

Author information

Authors and Affiliations



Braa Hajjar performed the experiments and collected the data. Braa Hajjar and Jieyu Zuo analyzed the data and wrote original manuscript; Chulhun Park, Shirzad Azarmi, Daniela Amaral Silva, and Nadia Araci Bou-Chacra contributed to discussion and writing—review and editing; Raimar Lobenberg contributed to conceptualization, writing—review and editing, supervision, project administration, and funding acquisition. All the authors reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to Raimar Löbenberg.

Ethics declarations


The authors declare that this article does not contain any studies with human and animal subjects performed by any of the authors. Dr. Azarmi and Dr. Löbenberg are co-founders of RS Therapeutics Inc.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (MP4 3506 KB)

Supplementary file2 (MP4 7682 KB)

Supplementary file3 (MP4 1578 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hajjar, B., Zuo, J., Park, C. et al. In Vitro Evaluation of a Foamable Microemulsion Towards an Improved Topical Delivery of Diclofenac Sodium. AAPS PharmSciTech 23, 102 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI:


  • topical delivery system
  • microemulsion
  • foam
  • diclofenac sodium