• RANIA YEHIA Department of Pharmaceutics and Industrial Pharmacy, The British University in Egypt, Cairo, Egypt.
  • DALIA A ATTIA Department of Pharmaceutics and Industrial Pharmacy, The British University in Egypt, Cairo, Egypt.


Microemulsion (ME) systems are now considered of the most successful transdermal drug delivery systems. This is due to their nanodroplets size in the one hand and to their composition that enables the use of several mechanistically penetration enhancers in the same formulation on the other hand. This work summarizes the types, properties, and the merits of the use of MEs for transdermal delivery and reviews the successful studies that were performed to deliver several drugs through this important route during the past 10–12 years.

Keywords: transdermal delivery, skin penetration, penetration enhancing, microemulsion


1. Hathout RM, Elshafeey AH. Development and characterization of colloidal soft nano-carriers for transdermal delivery and bioavailability enhancement of an angiotensin II receptor blocker. Eur J Pharm Biopharm 2012;82:230-40.
2. Hoar TP, Schulman JH. Transparent water-in-oil dispersions: The oleopathic hydro-micelle. Nature 1943;152:102-3.
3. Barry BW. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci 2001;14:101-14.
4. Menon GK. New insights into skin structure: Scratching the surface. Adv Drug Deliv Rev 2002;54:S3-17.
5. Freinkel RK, Woodley DT. The Biology of the Skin. Boca Raton: CRC Press; 2001.
6. Lai-Cheong JE, McGrath JA. Structure and function of skin, hair and nails. Medicine 2009;37:223-6.
7. Matsui T, Amagai M. Dissecting the formation, structure and barrier function of the stratum corneum. Int Immunol 2015;27:269-80.
8. Michaels S, Chandrasekaran SK, Shaw JE. Drug permeation through human skin: Theory and in vitro experimental measurement. AIChE J 1975;21:985-96.
9. FoldvariM. Non-invasive administration of drugs through the skin: Challenges in delivery system design. Pharm Sci Technol Today 2000;3:417-25.
10. Ya-Xian Z, SuetakeT, Tagami H. Number of cell layers of the stratum corneum in normal skin relationship to the anatomical location on the body, age, sex and physical parameters. Arch Dermatol Res 1999;291:555-9.
11. Riviere JE, Papich MG. Potential and problems of developing transdermal patches for veterinary applications. Adv Drug Deliv Rev 2001;50:175-203.
12. Verdier-Sevrain S, Bonte F. Skin hydration: A review on its molecular mechanisms. J Cosmet Dermatol 2007;6:75-82.
13. Igarashi T, Nishino K, Nayar SK. The appearance of human skin: A survey. Found Trends Comput Graph Vis 2007;3:1-95.
14. Juan EC, Rodríguez-Cruz IM, Domínguez-Delgado CL, Díaz- Torres R, Revilla-Vázquez AL, Aléncaster NC. Nanocarrier systems for transdermal drug delivery. In: Recent Advances in Novel Drug Carrier Systems. Croatia: Intech Open; 2012.
15. Bolzinger MA, Briancon S, Pelletier J, Chevalier Y. Penetration of drugs through skin, a complex rate-controlling membrane. Curr Opin Colloid Interface Sci 2012;17:156-65.
16. Patzelt A, Lademann J. The increasing importance of the hair follicle route in dermal and transdermal drug delivery. In: Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement. Berlin; Heidelberg: Springer; 2015. p. 43-53.
17. Cevc PG, Bachhawat BK. Transdermal immunisation with an integral membrane component, gap junction protein, by means of ultradeformable drug carriers, transfersomes. Vaccine 1998;16:188-95.
18. Kalluri H, Banga AK. Formation and closure of microchannels in skin following microporation. Pharm Res 2011;28:82-94.
19. El-Nabarawi MA, Shaker DS, Attia DA, Hamed SA, In vitro skin permeation and biological evaluation of lornoxicam monolithic transdermal patches. Int J Pharm Pharm Sci 2013;5:242-8.
20. Lopez RF, Seto JE, Blankschtein D, Langer R. Enhancing the transdermal delivery of rigid nanoparticles using the simultaneous application of ultrasound and sodium lauryl sulfate. Biomaterials 2011;32:933-41.
21. Hathout RM, Woodman TJ, Mansour S, Mortada ND, Geneidi AS, Guy RH. Microemulsion formulations for the transdermal delivery of testosterone. Eur J Pharm Sci 2010;40:188-96.
22. Caserta S, Campello S, Tomaiuolo G, Sabetta L, Guido S. A methodology to study chemotaxis in 3-D collagen gels. AIChE J 2013;59:4025-35.
23. Caserta VS, Russo I, Preziosi V, Ciacci C, Guido S. A novel chemotaxis assay in 3-D collagen gels by time-lapse microscopy. PLoS One 2012;7:e52251.
24. Moser K, Kriwet K, Kalia YN, Guy RH. Stabilization of supersaturated solutions of a lipophilic drug for dermal delivery. Int J Pharm 2001;224:169-76.
25. Chen X, Gregoire S, Formanek F, Galey JB, Rigneault H. Quantitative 3D molecular cutaneous absorption in human skin using label free nonlinear microscopy. J Control Release 2015;200:78-86.
26. Bharkatiya M, Nema R. Skin penetration enhancement techniques. J Young Pharm 2009;1:110.
27. Williams C, Barry BW. Penetration enhancers. Adv Drug Deliv Rev 2012;64:128-37.
28. El-Housiny S, Eldeen MA, El-Attar YA, Salem HA, Attia D, Bendas ER, et al. Fluconazole-loaded solid lipid nanoparticles topical gel for treatment of pityriasis versicolor: Formulation and clinical study. Drug Deliv 2018;25:78-90.
29. Changez M, Varshney M, Chander J, Dinda AK. Effect of the composition of lecithin/n-propanol/isopropyl myristate/water microemulsions on barrier properties of mice skin for transdermal permeation of tetracaine hydrochloride: In vitro. Colloids Surf B Biointerfaces 2006;50:18-25.
30. Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Adv Colloid Interface Sci 2006;123:369-85.
31. Lopes LB. Overcoming the cutaneous barrier with microemulsions. Pharmaceutics 2014;6:52-77.
32. Muzaffar FA, Singh UK, Chauhan LA. Review on microemulsion as futuristic drug delivery Int J Pharm Pharm Sci 2013;5:39-53.
33. Lindman B, Danielson I. The definition of microemulsion. Colloid Surf 1981;3:391-2.
34. Callender SP, Mathews JA, Kobernyk K, Wettig SD. Microemulsion utility in pharmaceuticals: Implications for multi-drug delivery. Int J Pharm 2017;526:425-42.
35. Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev 2000;45:89-121.
36. Kreilgaard M. Influence of microemulsions on cutaneous drug delivery. Adv Drug Deliv Rev 2002;54:S77-98.
37. Winsor PA. Hydrotropy, solubilisation and related emulsification processes. Trans Faraday Soc 1948;44:376-98.
38. Bhattacharya R, Mukhopadhyay S, Kothiyal P. Review on microemulsion-as a potential novel drug delivery system. World J Pharm Pharm Sci 2016;5:700-29.
39. Singh PK, Iqubal MK, Shukla VK, Shuaib M. Microemulsions: Current trends in novel drug delivery systems. J Pharm Chem Biol Sci 2014;1:39-51.
40. Ghosh PK, Murthy RS. Microemulsions: A potential drug delivery system. Curr Drug Deliv 2006;3:167-80.
41. Talegaonkar S, Azeem A, Ahmad FJ, Khar RK, Pathan SA, Khan ZI. Microemulsions: A novel approach to enhanced drug delivery. Recent Pat Drug Deliv Formul 2008;2:238-57.
42. Aungst J. Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or presystemic metabolism. J Pharm Sci 1993;82:979-87.
43. Scolari PP, Gasco MR. Transdermal permeation of apomorphine through hairless mouse skin from microemulsions. Int J Pharm 2001;226:47-51.
44. Pradhan M, Singh D, Singh MR. Novel colloidal carriers for psoriasis: Current issues, mechanistic insight and novel delivery approaches. J Control Release 2013;170:380-95.
45. Sintov C, Shapiro L. New microemulsion vehicle facilitates percutaneous penetration in vitro and cutaneous drug bioavailability in vivo. J Control Release 2004;95:173-83.
46. Escribano A, Calpena C, Queralt J, Obach R, Doménech J. Assessment of diclofenac permeation with different formulations: Anti-inflammatory study of a selected formula. Eur J Pharm Sci 2003;19:203-10.
47. Trotta M, Ugazio E, Peira E, Pulitano C. Influence of ion pairing on topical delivery of retinoic acid from microemulsions. J Control Release 2003;86:315-21.
48. Kahlweit M, Busse G, Faulhaber B. Preparing microemulsions with alkyl monoglucosides and the role of n-alkanols. Langmuir 1995;11:3382-7.
49. Gadhave D, Waghmare JT. A short review on microemulsion and its application in extraction of vegetable oil. Int J Res Eng Tech 2014;3:147-58.
50. Yin YM, Cui FD, Mu CF, Choi MK, Kim JS, Chung SJ, et al. Docetaxel microemulsion for enhanced oral bioavailability: Preparation and in vitro and in vivo evaluation. J Control Release 2009;140:86-94.
51. Zhao X, Liu JP, Zhang X, Li Y. Enhancement of transdermal delivery of theophylline using microemulsion vehicle. Int J Pharm 2006;327:58-64.
52. Djekic L, Primorac M. The influence of cosurfactants and oils on the formation of pharmaceutical microemulsions based on PEG-8 caprylic/ capric glycerides. Int J Pharm 2008;352:231-9.
53. Lawrence MJ. Surfactant systems: Microemulsions and vesicles as vehicles for drug delivery. Eur J Drug Metab Pharmacokinet 1994;19:257-69.
54. Tenjarla S. Microemulsions: An overview and pharmaceutical applications. Crit Rev Ther Drug Carrier Syst 1999;16:461-521.
55. Alany RG, Rades T, Agatonovic-Kustrin S, Davies NM, Tucker IG. Effects of alcohols and diols on the phase behaviour of quaternary systems. Int J Pharm 2000;196:141-5.
56. Aboofazeli R, Lawrence CB, Wicks SR, Lawrence MJ. Investigations into the formation and characterization of phospholipid microemulsions. III. Pseudo-ternary phase diagrams of systems containing water-lecithin-isopropyl myristate and either an alkanoic acid, amine, alkanediol, polyethylene glycol alkyl ether or alcohol as cosurfactant. Int J Pharm 1994;111:63-72.
57. Alberti I, Kalia YN, Naik A, Bonny JD, Guy RH. Effect of ethanol and isopropyl myristate on the availability of topical terbinafine in human stratum corneum, in vivo. Int J Pharm 2001;219:11-9.
58. Peltola S, Saarinen-Savolainen P, Kiesvaara J, Suhonen TM, Urtti A. Microemulsions for topical delivery of estradiol. Int J Pharm 2003;254:99-107.
59. Hathout RM, Mansour S, Mortada ND, Geneidi AS, Guy RH. Uptake of microemulsion components into the stratum corneum and their molecular effects on skin barrier function. Mol Pharm 2010;7:1266-73.
60. Spernath A, Aserin A. Microemulsions as carriers for drugs and nutraceuticals. Adv Colloid Interface Sci 2006;128:47-64.
61. Surabhi O, Katare P, Sushma D. Lecithinised microemulsions for topical delivery of Tretinoin. Int J Drug Dev Res 2010;24:711-9.
62. Lee SY, Teo CC, Tan WJ, Lim HY, Lim HH, Teo SY. Lipid microemulsion-based hydrogels for effective topical delivery of phenytoin. Int J Pharm Pharm Sci 2016;8:240-6.
63. Liuzzi R, Carciati A, Guido S, Caserta S. Transport efficiency in transdermal drug delivery: What is the role of fluid microstructure? Colloids Surf B Biointerfaces 2016;139:294-305.
64. Jamal TD, Vyumvuhore R, Manfait M, Baillet-Guffroy A. Hydration effects on the barrier function of stratum corneum lipids: Raman analysis of ceramides 2, III and 5. Analyst 2013;138:6582-8.
65. Lademann PJ, Richter H, Darvin ME, Schanzer S, Thiede G, Sterry W, et al. In vivo investigations on the penetration of various oils and their influence on the skin barrier. Skin Res Technol 2012;18:364-9.
66. Bucks D, Maibach HI. Occlusion does not uniformly enhance penetration in vivo. Drugs Pharm Sci 1999;97:81-106.
67. Forster M, Bolzinger MA, Fessi H, Briancon S. Topical delivery of cosmetics and drugs. Molecular aspects of percutaneous absorption and delivery. Eur J Dermatol 2009;19:309-23.
68. Benson HA. Transdermal drug delivery: Penetration enhancement techniques. Curr Drug Deliv 2005;2:23-33.
69. Gupta RR, Jain SK, Varshney M. AOT water-in-oil microemulsions as a penetration enhancer in transdermal drug delivery of 5-fluorouracil. Colloids Surf B Biointerfaces 2005;41:25-32.
70. Yuan Y, Li SM, Mo FK, Zhong DF. Investigation of microemulsion system for transdermal delivery of meloxicam. Int J Pharm 2006;321:117-23.
71. Junyaprasert VB, Boonme P, Songkro S, Krauel K, Rades T. Transdermal delivery of hydrophobic and hydrophilic local anesthetics from o/w and w/o Brij 97-based microemulsions. J Pharm Pharm Sci 2007;10:288-98.
72. Junyaprasert VB, Boonme P, Wurster DE, Rades T. Aerosol OT microemulsions as carriers for transdermal delivery of hydrophobic and hydrophilic local anesthetics. Drug Deliv 2008;15:323-30.
73. Bergamante FV, Ceschel GC, Ronchi C, De Moraes CA. Control of transdermal permeation of hydrocortisone acetate from hydrophilic and lipophilic formulations. AAPS Pharm Sci Tech 2008;9:762-8.
74. Gannu R, Palem CR, Yamsani VV, Yamsani SK, Yamsani MR. Enhanced bioavailability of lacidipine via microemulsion based transdermal gels: Formulation optimization, ex vivo and in vivo characterization. Int J Pharm 2010;388:231-41.
75. Liu H, Chang FY, Hung DK. Terpene microemulsions for transdermal curcumin delivery: Effects of terpenes and cosurfactants. Colloids Surf B Biointerfaces 2011;82:63-70.
76. Sintov C. Transdermal delivery of curcumin via microemulsion. Int J Pharm 2015;481:97-103.
77. Wang X, Xue M, Gu J, Fang X, Sha X. Transdermal microemulsion drug delivery system for impairing male reproductive toxicity and enhancing efficacy of Tripterygium wilfordii Hook f. Fitoterapia 2012;83:690-8.
78. Hathout RM, Nasr M. Transdermal delivery of betahistine hydrochloride using microemulsions: Physical characterization, biophysical assessment, confocal imaging and permeation studies. Colloids Surf B Biointerfaces 2013;110:254-60.
79. Al Abood RM, Talegaonkar S, Tariq M, Ahmad FJ. Microemulsion as a tool for the transdermal delivery of ondansetron for the treatment of chemotherapy induced nausea and vomiting. Colloids Surf B Biointerfaces 2013;101:143-51.
80. Fouad SA, Basalious EB, El-Nabarawi MA, Tayel SA. Microemulsion and poloxamer microemulsion-based gel for sustained transdermal delivery of diclofenac epolamine using in-skin drug depot: In vitro in vivo evaluation. Int J Pharm 2013;453:569-78.
81. Mostafa M, Ammar NM, Abd El-Alim SH, El-anssary AA. Transdermal microemulsions of Glycyrrhiza glabra L.: Characterization, stability and evaluation of antioxidant potential. Drug Deliv 2014;21:130-9.
82. Mura P, Bragagni M, Mennini N, Cirri M, Maestrelli F. Development of liposomal and microemulsion formulations for transdermal delivery of clonazepam: Effect of randomly methylated ?-cyclodextrin. Int J Pharm 2014;475:306-14.
83. Ge S, Lin Y, Lu H, Li Q, He J, Chen B, et al. Percutaneous delivery of econazole using microemulsion as vehicle: Formulation, evaluation and vesicle-skin interaction. Int J Pharm 2014;465:120-31.
84. Sapra SB, Tiwary AK. Microemulsion transdermal formulation for simultaneous delivery of valsartan and nifedipine: Formulation by design. AAPS Pharm Sci Tech 2016;18:1901-16.
85. Ren CL, Chen G. Formulation optimization and ex vivo and in vivo evaluation of celecoxib microemulsion based gel for transdermal delivery. AAPS Pharm Sci Tech 2016;18:1960-71.
86. Seok SH, Lee SA, Park ES. Formulation of a microemulsion-based hydrogel containing celecoxib. J Drug Deliv Sci Technol 2017;4:459-71.
87. Yehia R, Hathout RM, Attia DA, Elmazar MM, Mortada ND. Anti-tumor efficacy of an integrated methyl dihydrojasmonate transdermal microemulsion system targeting breast cancer cells: In vitro and in vivo studies. Colloids Surf B Biointerfaces 2017;155:512-21.
88. Alyoussef AJ, Talhouni AA. In vivo and in vitro study of transdermal application of diclofenac sodium using nonionic microemulsions as colloidal drug delivery systems. J Drug Deliv Sci Technol 2018;43:27-33.
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