Chemical Penetration Enhancers: Classification and Mode of Action

  • Nina DragicevicEmail author
  • Jelena Predic Atkinson
  • Howard I. Maibach


Chemical penetration enhancers have been studied for a long time as a means to increase the transport of a drug across the skin barrier. They exert their effect by using a range of mechanisms such as disrupting the lipid bilayer structure in the stratum corneum (SC) and thereby increasing the drug’s diffusion coefficient, extracting lipids from the SC, altering the solvent nature of the SC and consequently modifying the drug partitioning coefficient, acting on intracellular keratin, etc. Chemical enhancers can be categorised into different groups on the basis of their chemical structure. Solvents like alcohols and polyols mainly increase drug’s solubility in the SC and improve partitioning of the drug into the SC. Furthermore, some solvents (dimethyl sulphoxide (DMSO), ethanol) may extract lipids, making the SC more permeable as they form aqueous channels. Laurocapram (Azone®) and oleic acid are examples of chemical enhancers that can insert themselves into the SC lipid bilayer structures and disrupt the packing of the lipids. The result of this is that the lipid structure of the SC becomes more fluid and the diffusion coefficient of the permeant is increased. Ionic surfactants and DMSO also interact with the keratin structure in the corneocytes. This opens up the tight protein structure and leads to an increased diffusion coefficient through the corneocytes, being however not of great importance as the intercellular route, and not the intracellular route, is the major penetration pathway through the SC. Despite being very effective in enhancing drug permeation through the skin, many chemical penetration enhancers have a limited use in topical and transdermal drug delivery systems because they can cause skin irritation.


Chemical penetration enhancer Skin Stratum corneum Mode of action Terpenes Ethanol Lipid bilayer 


  1. Akimoto T, Kawahara K, Nagase Y, Aoyagi T (2001) Polymeric transdermal drug penetration enhancer. The enhancing effect of oligodimethylsiloxane containing a glucopyranosyl end group. J Control Release 77:49–57CrossRefPubMedGoogle Scholar
  2. Aqil M, Ahad A, Sultana Y, Ali A (2007) Status of terpenes as skin penetration enhancers. Drug Discov Today 12(23–24):1061–1067CrossRefPubMedGoogle Scholar
  3. Asbill CS, Michniak BB (2000) Percutaneous penetration enhancers: local versus transdermal activity. Pharm Sci Technol Today 3(1):36–41CrossRefPubMedGoogle Scholar
  4. Aungst BJ (1989) Structure/effect studies of fatty acid isomers as skin penetration enhancers and skin irritants. Pharm Res 6(3):244–247CrossRefPubMedGoogle Scholar
  5. Aungst BJ, Rogers N, Shefter E (1986) Enhancement of naloxone penetration through human skin in vitro using fatty acids, fatty alcohols, surfactants, sulfoxides and amides. Int J Pharm 33(1–3):225–234CrossRefGoogle Scholar
  6. Babu RJ, Pandit JK (2005) Effect of penetration enhancers on the transdermal delivery of bupranolol through rat skin. Drug Deliv 12:165–169CrossRefPubMedGoogle Scholar
  7. Baek JS, Lim JH, Kang JS, Shin SC, Jung SH, Cho CW (2013) Enhanced transdermal drug delivery of zaltoprofen using a novel formulation. Int J Pharm 453(2):358–362CrossRefPubMedGoogle Scholar
  8. Barry BW (1983) Dermatological formulations: percutaneous absorption. Marcel Dekker, New YorkGoogle Scholar
  9. Barry BW (1987) Mode of action of penetration enhancers in human skin. J Control Release 6(1):85–97CrossRefGoogle Scholar
  10. Barry BW (1991) Lipid–protein-partitioning theory of skin penetration enhancement. J Control Release 15:237–248CrossRefGoogle Scholar
  11. Barry BW (2001) Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci 2:101–114CrossRefGoogle Scholar
  12. Barry BW (2004) Breaching the skin’s barrier to drugs. Nat Biotechnol 22(2):165–167CrossRefPubMedGoogle Scholar
  13. Benson HA (2005) Transdermal drug delivery: penetration enhancement techniques. Curr Drug Deliv 2(1):23–33CrossRefPubMedGoogle Scholar
  14. Berner B, Mazzenga GC, Otte JH, Steffens RJ, Juang R-H, Ebert CD (1989) Ethanol: water mutually enhanced transdermal therapeutic system: II. Skin permeation of ethanol and nitroglycerin. J Pharm Sci 78:402–407CrossRefPubMedGoogle Scholar
  15. Bonnist EY, Gorce JP, Mackay C, Pendlington RU, Pudney PD (2011) Measuring the penetration of a skin sensitizer and its delivery vehicles simultaneously with confocal Raman spectroscopy. Skin Pharmacol Physiol 24(5):274–283CrossRefPubMedGoogle Scholar
  16. Bouwstra JA, Peschier LJC, Brussee J, Boddé HE (1989) Effect of N-alkyl-azocycloheptan-2-ones including azone on the thermal behaviour of human stratum corneum. Int J Pharm 52:47–54CrossRefGoogle Scholar
  17. Bouwstra JA, de Vries MA, Gooris GS, Bras W, Brussee J, Ponec M (1991) Thermodynamic and structural aspects of skin barrier. J Control Release 1:209–220CrossRefGoogle Scholar
  18. Bouwstra JA, de Graaff A, Gooris GS, Nijsse J, Wiechers JW, van Aelst AC (2003) Water distribution and related morphology in human stratum corneum at different hydration levels. J Invest Dermatol 120(5):750–758CrossRefPubMedGoogle Scholar
  19. Brain KR, Green DM, Dykes PJ, Marks R, Bola TS (2006) The role of menthol in skin penetration from topical formulations of ibuprofen 5% in vivo. Skin Pharmacol Physiol 19:17–21CrossRefPubMedGoogle Scholar
  20. Brinkmann I, Müller-Goymann CC (2003) Role of isopropyl myristate, isopropyl alcohol and a combination of both in hydrocortisone permeation across the human stratum corneum. Skin Pharmacol Appl Skin Physiol 16:393–404CrossRefPubMedGoogle Scholar
  21. Brinkmann I, Müller-Goymann CC (2005) An attempt to clarify the influence of glycerol, propylene glycol, isopropyl myristate and a combination of propylene glycol and isopropyl myristate on human stratum corneum. Pharmazie 60(3):215–220PubMedGoogle Scholar
  22. Bucks D, and Maibach HI (1999) Occlusion Does Not Uniformly Enhance Penetration In Vivo. p. 81–105 in Percutaneous Absorption, 3rd ed., Bronaugh RL, and Maibach HI, eds. New York: Marcel Dekker, Inc.Google Scholar
  23. Cázares-Delgadillo J, Naik A, Kalia YN, Quintanar-Guerrero D, Ganem-Quintanar A (2005) Skin permeation enhancement by sucrose esters: a pH-dependent phenomenon. Int J Pharm 297(1–2):204–212CrossRefPubMedGoogle Scholar
  24. Choi J, Choi MK, Chong S, Chung SJ, Shim CK, Kim DD (2012) Effect of fatty acids on the transdermal delivery of donepezil: in vitro and in vivo evaluation. Int J Pharm 422(1–2):83–90CrossRefPubMedGoogle Scholar
  25. Cornwell PA, Barry BW (1994) Sesquiterpene components of volatile oils as skin penetration enhancers for the hydrophilic permeant 5-fluorouracil. J Pharm Pharmacol 46(4):261–269CrossRefPubMedGoogle Scholar
  26. Cornwell PA, Barry BW, Bouwstra JA, Gooris GS (1996) Modes of action of terpene penetration enhancers in human skin; differential scanning calorimetry, small-angle X-ray diffraction and enhancer uptake studies. Int J Pharm 127:9–26CrossRefGoogle Scholar
  27. Du Plessis J, Pugh WJ, Judefeind A, Hadgraft J (2001) The effect of hydrogen bonding on diffusion across model membranes: consideration of the number of H-bonding groups. Eur J Pharm Sci 13:135–141CrossRefPubMedGoogle Scholar
  28. Elias PM, Tsai J, Menon GK, Holleran WM, Feingold KR (2002) The potential of metabolic interventions to enhance transdermal drug delivery. J Investig Dermatol Symp Proc 7(1):79–85CrossRefPubMedGoogle Scholar
  29. Escobar-Chávez JJ, Quintanar-Guerrero D, Ganem-Quintanar A (2005) In vivo skin permeation of sodium naproxen formulated in pluronic F-127 gels: effect of Azone and Transcutol. Drug Dev Ind Pharm 31(4–5):447–454CrossRefPubMedGoogle Scholar
  30. Furuishi T, Kato Y, Fukami T, Suzuki T, Endo T, Nagase H, Ueda H, Tomono K (2013) Effect of terpenes on the skin permeation of lomerizine dihydrochloride. J Pharm Pharm Sci 16(4):551–563PubMedGoogle Scholar
  31. Gao S, Singh J (1998) In vitro percutaneous absorption enhancement of a lipophilic drug tamoxifen by terpenes. J Control Release 51(2–3):193–199CrossRefPubMedGoogle Scholar
  32. Ghafourian T, Zandasrar P, Hamishekar H, Nokhodchi A (2004) The effect of penetration enhancers on drug delivery through skin: a QSAR study. J Control Release 99:113–125CrossRefPubMedGoogle Scholar
  33. Goates CY, Knutson K (1994) Enhanced permeation of polar compounds through human epidermis. I. Permeability and membrane structural changes in the presence of short chain alcohol. Biochim Biophys Acta 1195:169–179CrossRefPubMedGoogle Scholar
  34. Golden GM, McKie JE, Potts RO (1987) Role of stratum corneum lipid fluidity in transdermal drug flux. J Pharm Sci 98:4085–4099Google Scholar
  35. Guillard EC, Laugel C, Baillet-Guffroy A (2009) Molecular interactions of penetration enhancers within ceramides organization: a FTIR approach. Eur J Pharm Sci 36:192–199CrossRefPubMedGoogle Scholar
  36. Hadgraft J (1999) Passive enhancement strategies in topical and transdermal drug delivery. Int J Pharm 184(1):1–6CrossRefPubMedGoogle Scholar
  37. Hadgraft J, Peck J, Williams D, Pugh J, Allan G (1996) Mechanisms of action of skin penetration enhancers/retarders: azone and analogues. Int J Pharm 141(1–2):17–25CrossRefGoogle Scholar
  38. Harrison JE, Watkinson AC, Green DM, Hadgraft J, Brain K (1996a) The relative effect of azone and transcutol on permeant diffusivity and solubility in human stratum corneum. Pharm Res 13(4):542–546CrossRefPubMedGoogle Scholar
  39. Harrison JE, Groundwater PW, Brain K, Hadgraft J (1996b) Azone® induced fluidity in human stratum corneum. A fourier transform infrared spectroscopy investigation using the perdeuterated analogue. J Control Release 41(3):283–290CrossRefGoogle Scholar
  40. Hatta I, Nakazawa H, Obata Y, Ohta N, Inoue K, Yagi N (2010) Novel method to observe subtle structural modulation of stratum corneum on applying chemical agents. Chem Phys Lipids 163:381–389CrossRefPubMedGoogle Scholar
  41. Heard CM, Kung D, Thomas CP (2006) Skin penetration enhancement of mefenamic acid by ethanol and 1,8-cineole can be explained by the ‘pull’ effect. Int J Pharm 321:167–170CrossRefPubMedGoogle Scholar
  42. Herman A, Herman AP (2015) Essential oils and their constituents as skin penetration enhancer for transdermal drug delivery: a review. J Pharm Pharmacol 67(4):473–485CrossRefPubMedGoogle Scholar
  43. Hoelgaard A, Mollgaard B (1985) Dermal drug delivery – improvement by choice of vehicle or drug derivative. J Control Release 2:111–120CrossRefGoogle Scholar
  44. Hori M, Satoh S, Maibach HI, Guy RH (1991) Enhancement of propranolol hydrochloride and diazepam skin absorption in vitro: effect of enhancer lipophilicity. J Pharm Sci 80:32–35CrossRefPubMedGoogle Scholar
  45. Ibrahim SA, Li SK (2010) Efficiency of fatty acids as chemical penetration enhancers: mechanisms and structure enhancement relationship. Pharm Res 27(1):115–125PubMedCentralCrossRefPubMedGoogle Scholar
  46. Jain AK, Thomas NS, Panchagnula R (2002) Transdermal drug delivery of imipramine hydrochloride: I. Effect of terpenes. J Control Release 79:93–101CrossRefPubMedGoogle Scholar
  47. Jampilek J, Brychtova K (2012) Azone analogues: classification, design, and transdermal penetration principles. Med Res Rev 32(5):907–947CrossRefPubMedGoogle Scholar
  48. Joo HH, Kim JC, Lee HY (2008) In vitro permeation study of hinokitiol: effects of vehicles and enhancers. Drug Deliv 15:19–22CrossRefPubMedGoogle Scholar
  49. Kadir R, Stempler D, Liron Z, Cohen S (1987) Delivery of theophylline into excised human skin from alkanoic acid solutions: a ‘push– pull’ mechanism. J Pharm Sci 76:774–779CrossRefPubMedGoogle Scholar
  50. Kanikkannan N, Kandimalla K, Lamba SS, Singh M (2000) Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery. Curr Med Chem 7:593–608CrossRefPubMedGoogle Scholar
  51. Karande P, Mitragotri S (2009) Enhancement of transdermal drug delivery via synergistic action of chemicals. Biochim Biophys Acta 1788(11):2362–2373CrossRefPubMedGoogle Scholar
  52. Kasting GB, Francis WR, Roberts GE (1993) Skin penetration enhancement of triprolidine base by propylene glycol. J Pharm Sci 82(5):551–552CrossRefPubMedGoogle Scholar
  53. Krishnaiah YS, Al-Saidan SM, Chandrasekha DV, Rama B (2006) Effect of nerodilol and carvone on in vitro permeation of nicorandil across rat epidermal membrane. Drug Dev Ind Pharm 32:423–435CrossRefPubMedGoogle Scholar
  54. Lane ME (2013) Skin penetration enhancers. Int J Pharm 447:12–21CrossRefPubMedGoogle Scholar
  55. Lane ME, Santos P, Watkinson AC, Hadgraft J (2012) Passive skin permeation enhancement. In: Benson HE, Watkinson AC (eds) Topical and transdermal drug delivery. Wiley, Hoboken, pp 23–42CrossRefGoogle Scholar
  56. Leopold CS, Lippold BC (1995) An attempt to clarify the mechanism of the penetration enhancing effects of lipophilic vehicles with differential scanning calorimetry (DSC). J Pharm Pharmacol 47(4):276–281CrossRefPubMedGoogle Scholar
  57. Megrab NA, Williams AC, Barry BW (1995) Oestradiol permeation across human skin, silastic and snake skin membranes: the effects of ethanol/water co-solvent system. Int J Pharm 116:101–112CrossRefGoogle Scholar
  58. Menczel EM (1995) Delipidization of the cutaneous permeability barrier and percutaneous penetration. In: Smith EW, Maibach HI (eds) Percutaneous penetration enhancers. CRC Press, Boca Raton, pp 383–392Google Scholar
  59. Moghadam SH, Saliaj E, Wettig SD, Dong C, Ivanova MV, Huzil JT, Foldvari M (2013) Effect of chemical permeation enhancers on stratum corneum barrier lipid organizational structure and interferon alpha permeability. Mol Pharm 10(6):2248–2260CrossRefPubMedGoogle Scholar
  60. Moghimi HR, Williams AC, Barry BW (1997) A lamellar matrix model for stratum corneum intercellular lipids. V. Effect of terpene penetration enhancers on the structure and thermal behaviour of the matrix. Int J Pharm 146:41–54CrossRefGoogle Scholar
  61. Morimoto H, Wada Y, Seki T, Sugibayashi K (2002) In vitro skin permeation of morphine hydrochloride during the finite application of penetration-enhancing system containing water, ethanol and L-menthol. Biol Pharm Bull 25:134–136CrossRefPubMedGoogle Scholar
  62. Mura P, Faucci MT, Bramanti G, Corti P (2000) Evaluation of transcutol as a clonazepam transdermal permeation enhancer from hydrophilic gel formulations. Eur J Pharm Sci 9(4):365–372CrossRefPubMedGoogle Scholar
  63. Narishetty ST, Panchagnula R (2004) Transdermal delivery of zidovudine: effect of terpenes and their mechanism of action. J Control Release 95(3):367–379CrossRefPubMedGoogle Scholar
  64. Narishetty ST, Panchagnula R (2005) Effect of L-menthol and 1,8-cineole on phase behavior and molecular organization of SC lipids and skin permeation of zidovudine. J Control Release 102(1):59–70CrossRefPubMedGoogle Scholar
  65. Notman R, Anwar J, Briels WJ, Noro MG, den Otter WK (2008) Simulations of skin barrier function: free energies of hydrophobic and hydrophilic transmembrane pores in ceramide bilayers. Biophys J. 95(10):4763–71.Google Scholar
  66. Obata Y, Takayama K, Machida Y, Nagai T (1991) Combined effect of cyclic monoterpenes and ethanol on percutaneous absorption of diclofenac sodium. Drug Des Discov 8:137–144PubMedGoogle Scholar
  67. Obata Y, Utsumi S, Watanabe H, Suda M, Tokudome Y, Otsuka M, Takayama K (2010) Infrared spectroscopic study of lipid interaction in stratum corneum treated with transdermal absorption enhancers. Int J Pharm 389:18–23Google Scholar
  68. Okabe H, Obata Y, Takayama K, Nagai T (1990) Percutaneous absorption enhancing effect and skin irritation of monocyclic monoterpenes. Drug Des Deliv 6:229–238PubMedGoogle Scholar
  69. Ongpipattanakul B, Burnette RR, Potts RO, Francoeur ML (1991) Evidence that oleic acid exists in a separate phase within stratum corneum lipids. Pharm Res 7:350–354CrossRefGoogle Scholar
  70. Osborne DW, Henke JJ (1997) Skin penetration enhancers cited in the technical literature. Pharm Technol 21:58–66Google Scholar
  71. Patel RP, Gaiakwad DR, Patel NA (2014) Formulation, optimization, and evaluation of a transdermal patch of heparin sodium. Drug Discov Ther 8(4):185–193CrossRefPubMedGoogle Scholar
  72. Pershing LK, Lambert LD, Knutson K (1990) Mechanism of ethanol-enhanced estradiol permeation across human skin in vivo. Pharm Res 7(2):170–175CrossRefPubMedGoogle Scholar
  73. Pilgram GS, van der Meulen J, Gooris GS, Koerten HK, Bouwstra JA (2001) The influence of two azones and sebaceous lipids on the lateral organization of lipids isolated from human stratum corneum. Biochim Biophys Acta 1511(2):244–254CrossRefPubMedGoogle Scholar
  74. Pudney PD, Mélot M, Caspers PJ, Van Der Pol A, Puppels GJ (2007) An in vivo confocal Raman study of the delivery of trans retinol to the skin. Appl Spectrosc 61(8):804–811CrossRefPubMedGoogle Scholar
  75. Ridout G, Hinz RS, Hostynek JJ, Reddy AK, Wiersema RJ, Hodson CD, Lorence CR, Guy RH (1991) The effects of zwitterionic surfactants on skin barrier function. Fundam Appl Toxicol 16(1):41–50CrossRefPubMedGoogle Scholar
  76. Rizwan M, Aqil M, Ahad A, Sultana Y, Ali MM (2008) Transdermal delivery of valsartan: I. Effect of various terpenes. Drug Dev Ind Pharm 34:618–626 CrossRefPubMedGoogle Scholar
  77. Santos P, Watkinson AC, Hadgraft J, Lane ME (2012) Influence of penetration enhancer on drug permeation from volatile formulations. Int J Pharm 439(1–2):260–268CrossRefPubMedGoogle Scholar
  78. Shah DK, Khandavilli S, Panchagnula R (2008) Alteration of skin hydration and its barrier function by vehicle and permeation enhancers: a study using TGA, FTIR, TEWL and drug permeation as markers. Methods Find Exp Clin Pharmacol 30:499–512CrossRefPubMedGoogle Scholar
  79. Som I, Bhatia K, Yasir M (2012) Status of surfactants as penetration enhancers in transdermal drug delivery. J Pharm Bioallied Sci 4(1):2–9PubMedCentralCrossRefPubMedGoogle Scholar
  80. Song YH, Gwak HS, Chun IK (2009) The effects of terpenes on the permeation of lidocaine and ofloxacin from moisture-activated patches. Drug Deliv 16:75–81CrossRefPubMedGoogle Scholar
  81. Songkro S (2009) An overview of skin penetration enhancers: penetration enhancing activity, skin irritation potential and mechanism of action. Songklanakarin J Sci Technol 31(3):299–321Google Scholar
  82. Tanojo H, Bosvangeest A, Bouwstra JA, Junginger HE, Bodde HE (1997) In-vitro human skin barrier perturbation by oleic-acid – thermal-analysis and freeze-fracture electron-microscopy studies. Thermochim Acta 293(1–2):77–85CrossRefGoogle Scholar
  83. Tas C, Ozkan Y, Okyar A, Savaser A (2007) In vitro and ex vivo permeation studies of etodolac from hydrophilic gels and effect of terpenes as enhancers. Drug Deliv 14:453–459CrossRefPubMedGoogle Scholar
  84. Thomas NS, Panchagnula R (2003) Transdermal delivery of zidovudine: effect of vehicles on permeation across rat skin and their mechanism of action. Eur J Pharm Sci 18:71–79CrossRefPubMedGoogle Scholar
  85. Trottet L, Merly C, Mirza M, Hadgraft J, Davis AF (2004) Effect of finite doses of propylene glycol on enhancement of in vitro percutaneous permeation of loperamide hydrochloride. Int J Pharm 274(1–2):213–219CrossRefPubMedGoogle Scholar
  86. Vaddi HK, Ho PC, Chan YW, Chan SY (2002) Terpenes in propylene glycol as skin-penetration enhancers: permeation and partition of haloperidol, fourier transform infrared spectroscopy, and differential scanning calorimetry. J Pharm Sci 91:1639–1651CrossRefPubMedGoogle Scholar
  87. Van Hal DA, Jeremiasse E, Junginger HE, Spies F, Bouwstra JA (1996) Structure of fully hydrated human stratum corneum: a freeze fracture electron microscopy study. J Invest Dermatol 106:89–95CrossRefPubMedGoogle Scholar
  88. Watanabe H, Obata Y, Ishida K, Takayama K (2009) Effect of l-menthol on the thermotropic behavior of ceramide 2/cholesterol mixtures as a model for the intercellular lipids in stratum corneum. Colloids Surf B Biointerfaces 73:116–121CrossRefPubMedGoogle Scholar
  89. Watkinson RM, Herkenne C, Guy RH, Hadgraft J, Oliveira G, Lane ME (2009a) Influence of ethanol on the solubility, ionization and permeation characteristics of ibuprofen in silicone and human skin. Skin Pharmacol Physiol 22:15–21CrossRefPubMedGoogle Scholar
  90. Watkinson RM, Guy RH, Hadgraft J, Lane ME (2009b) Optimisation of cosolvent concentration for topical drug delivery – II: influence of propylene glycol on ibuprofen permeation. Skin Pharmacol Physiol 22:225–230CrossRefPubMedGoogle Scholar
  91. Williams AC, Barry BW (1989) Permeation, FTIR and DSC investigations of terpene penetration enhancers in human skin. J Pharm Pharmacol 41:12PGoogle Scholar
  92. Williams AC, Barry BW (1991) The enhancement index concept applied to terpene penetration enhancers for human skin and model lipophilic (oestradiol) and hydrophilic (5-fluorouracil) drugs. Int J Pharm 74:157–168CrossRefGoogle Scholar
  93. Williams AC, Barry BW (2004) Penetration enhancers. Adv Drug Deliv Rev 56(5):603–618CrossRefPubMedGoogle Scholar
  94. Yamane MA, Williams AC, Barry BW (1995) Terpene penetration enhancers in propylene glycol/water co-solvent systems: effectiveness and mechanism of action. J Pharm Pharmacol 47:978–989CrossRefPubMedGoogle Scholar
  95. Yamato K, Takahashi Y, Akiyama H, Tsuji K, Onishi H, Machida Y (2009) Effect of penetration enhancers on transdermal delivery of propofol. Biol Pharm Bull 32:267–274Google Scholar
  96. Zhao K, Singh J (1998) Mechanisms of percutaneous absorption of tamoxifen by terpenes: eugenol, D-limonene and menthone. J Control Release 55(2–3):253–260CrossRefPubMedGoogle Scholar
  97. Zhao K, Singh J (1999) In vitro percutaneous absorption enhancement of propranolol hydrochloride through porcine epidermis by terpenes/ethanol. J Control Release 62:359–366CrossRefPubMedGoogle Scholar
  98. Zhao K, Singh J (2000) Mechanism(s) of in vitro percutaneous absorption enhancement of tamoxifen by enhancers. J Pharm Sci 89(6):771–780CrossRefPubMedGoogle Scholar
  99. Zhao K, Singh S, Singh J (2001) Effect of menthone on the in vitro percutaneous absorption of tamoxifen and skin reversibility. Int J Pharm 219:177–181CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Nina Dragicevic
    • 1
    Email author
  • Jelena Predic Atkinson
    • 2
  • Howard I. Maibach
    • 3
  1. 1.Department of ProductionApoteka “Beograd” (Pharmacy “Belgrade”)BelgradeSerbia
  2. 2.LondonUK
  3. 3.Dermatology ClinicUniversity of California San FranciscoSan FranciscoUSA

Personalised recommendations