What are advantages and disadvantages of transdermal drug delivery system?

Papers of special note have been highlighted as:

▪ of interest

▪ ▪ of considerable interest

1. Jain PharmaBiotech report. Transdermal drug delivery-technologies, markets and companies. 2005. [Google Scholar]

2. Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotech. 2008;26(11):1261–1268. [PMC free article] [PubMed] [Google Scholar]

3. Martin E, editor. Remington’s Practice of Pharmacy. Mack Publishing Co; Easton, PA, USA: 2003. [Google Scholar]

4. Scheindlin S. Transdermal drug delivery: past, present, future. Mol Interv. 2004;4(6):308–312. [PubMed] [Google Scholar]

5. Cevc G, Vierl U. Nanotechnology and the transdermal route. A state of the art review and critical appraisal. J Control Release. 2010;141(11):277–299. [PubMed] [Google Scholar]

6. Tiwary AK, Sapra B, Jain S. Innovations in transdermal drug delivery: formulations and techniques. Recent Pat Drug Deliv Formul. 2007;1:23–36. [PubMed] [Google Scholar]

7. Samad A, Ullah Z, Alam MI, Wais M, Shams MS. Transdermal drug delivery system: patent reviews. Recent Pat Drug Deliv Formul. 2009;3(2):143–52. [PubMed] [Google Scholar]

8. Rizwan M, Aqil M, Talegaonkar S, Azeem A, Sultana Y, Ali A. Enhanced transdermal drug delivery techniques: an extensive review of patents. Recent Pat Drug Deliv Formul. 2009;3(2):105–124. [PubMed] [Google Scholar]

9. Prausnitz MR, Mitragotri S, Langer R. Current status and future potential of transdermal drug delivery. Nat Rev Drug Discov. 2004;3(2):115–124. [PubMed] [Google Scholar]

10. Banga AK. Microporation applications for enhancing drug delivery. Expert Opin Drug Deliv. 2009;6(4):343–54. [PubMed] [Google Scholar]

11. Kalluri H, Banga AK. Microneedles and transdermal drug delivery. J Drug Del Sci Tech. 2009;19(5):303–310. [Google Scholar]

12. Bos JD, Meinardi MMHM. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol. 2000;9(3):165–169. [PubMed] [Google Scholar]

13▪. Thong HY, Zhai H, Maibach HI. Percutaneous penetration enhancers: an overview. Skin Pharmacol Physiol. 2007;20(6):272–282. Recent review containing extensive list of popular chemical permeation enhancers. [PubMed] [Google Scholar]

14. Michaels AS, Chandrasekaran SK, Shaw JE. Drug permeation through human skin. Theory and in vitro experimental measurement. AIChE J. 1975;21(5):985–996. [Google Scholar]

15. Albery WJ, Hadgraft J. Percutaneous absorption: in vivo experiments. J Pharm Pharmacol. 1979;31(3):140–147. [PubMed] [Google Scholar]

16. Tojo K. Random brick model for drug transport across stratum corneum. J Pharm Sci. 1987;76(12):889–891. [PubMed] [Google Scholar]

17. Goffin V, Henry F, Pierard-Franchimont C, Pierard GE. Penetration enhancers assessed by corneoxenometry. Skin Pharmacol Appl Skin Physiol. 2000;13(5):280–284. [PubMed] [Google Scholar]

18. Barry BW. Lipid–protein-partitioning theory of skin penetration enhancement. J Control Release. 1991;15(3):237–248. [Google Scholar]

19. Karande P, Jain A, Ergun K, Kispersky V, Mitragotri S. Design principles of chemical penetration enhancers for transdermal drug delivery. Proc Natl Acad Sci USA. 2005;102(13):4688–4693. [PMC free article] [PubMed] [Google Scholar]

20. Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Adv Colloid Interface Sci. 2006;123–126:369–385. [PubMed] [Google Scholar]

21▪ ▪. Karande P, Jain A, Mitragotri S. Discovery of transdermal penetration enhancers by high-throughput screening. Nat Biotechnol. 2004;22(2):192–197. Identification of synergistic chemical permeation enhancer combinations through high-throughput screening. [PubMed] [Google Scholar]

22. Karande P, Jain A, Mitragotri S. Insights into synergistic interactions in binary mixtures of chemical permeation enhancers for transdermal drug delivery. J Control Release. 2006;115(1):85–93. [PubMed] [Google Scholar]

23. Hamilton JG. Needle phobia: a neglected diagnosis. J Fam Practice. 1995;41(2):169–175. [PubMed] [Google Scholar]

24. Burkoth TL, Bellhouse BJ, Hewson G, Longridge DJ, Muddle AG, Sarphie DF. Transdermal and transmucosal powdered drug delivery. Crit Rev Ther Drug Carrier Syst. 1999;16(4):331–384. [PubMed] [Google Scholar]

25. Schramm J, Mitragotri S. Transdermal drug delivery by jet injectors: energetics of jet formation and penetration. Pharm Res. 2002;19(11):1673–1679. [PubMed] [Google Scholar]

26. Bremseth DL, Pass F. Delivery of insulin by jet injection: recent observations. Diabetes Technol Ther. 2001;3(2):225–232. [PubMed] [Google Scholar]

27. Denne JR, Andrews KL, Lees DV, Mook W. A survey of patient preference for insulin jet injectors versus needle and syringe. Diabetes Educ. 1992;18(3):223–227. [PubMed] [Google Scholar]

28. Dean Hansi J, Fuller D, Osorio Jorge E. Powder and particle-mediated approaches for delivery of DNA and protein vaccines into the epidermis. Comp Immunol Microbiol Infect Dis. 2003;26(5–6):373–388. [PubMed] [Google Scholar]

29. Spencer JM. Microdermabrasion. Am J Clin Dermatol. 2005;6(2):89–92. [PubMed] [Google Scholar]

30. Fang JY, Lee WR, Shen SC, Fang YP, Hu CH. Enhancement of topical 5-aminolaevulinic acid delivery by erbium:YAG laser and microdermabrasion: a comparison with iontophoresis and electroporation. Br J Dermatol. 2004;151(1):132–140. [PubMed] [Google Scholar]

31. Fujimoto T, Shirakami K, Tojo K. Effect of microdermabrasion on barrier capacity of stratum corneum. Chem Pharm Bull. 2005;53(8):1014–1016. [PubMed] [Google Scholar]

32. Gill HS, Andrews SN, Sakthivel SK, et al. Selective removal of stratum corneum by microdermabrasion to increase skin permeability. Eur J Pharm Sci. 2009;38(2):95–103. [PMC free article] [PubMed] [Google Scholar]

33▪ ▪. Park JH, Lee JW, Kim YC, Prausnitz MR. The effect of heat on skin permeability. Int J Pharm. 2008;359(1–2):94–103. A study of the structural disruption of skin subjected to high temperature. [PMC free article] [PubMed] [Google Scholar]

34. Lee WR, Shen SC, Lai HH, Hu CH, Fang JY. Transdermal drug delivery enhanced and controlled by erbium:YAG laser: a comparative study of lipophilic and hydrophilic drugs. J Control Release. 2001;75(1–2):155–166. [PubMed] [Google Scholar]

35. Nelson JS, McCullough JL, Glenn TC, Wright WH, Liaw LH, Jacques SL. Mid-infrared laser ablation of stratum corneum enhances in vitro percutaneous transport of drugs. J Invest Dermatol. 1991;97(5):874–879. [PubMed] [Google Scholar]

36. Gomez C, Costela A, Garcia-Moreno I, Llanes F, Teijon JM, Blanco D. Laser treatments on skin enhancing and controlling transdermal delivery of 5-fluorouracil. Laser Surg Med. 2008;40(1):6–12. [PubMed] [Google Scholar]

37. Arora A, Prausnitz MR, Mitragotri S. Micro-scale devices for transdermal drug delivery. Int J Pharm. 2008;364(2):227–236. [PMC free article] [PubMed] [Google Scholar]

38. Henry S, McAllister DV, Allen MG, Prausnitz MR. Microfabricated microneedles: a novel approach to transdermal drug delivery. J Pharm Sci. 1998;87(8):922–925. [PubMed] [Google Scholar]

39. Sullivan SP, Murthy N, Prausnitz MR. Minimally invasive protein delivery with rapidly dissolving polymer microneedles. Adv Mater. 2008;20(5):933–938. [PMC free article] [PubMed] [Google Scholar]

40. Banks SL, Pinninti RR, Gill HS, Crooks PA, Prausnitz MR, Stinchcomb AL. Flux across microneedle-treated skin is increased by increasing charge of naltrexone and naltrexol in vitro. Pharm Res. 2008;25(7):1677–1685. [PMC free article] [PubMed] [Google Scholar]

41. Gill HS, Prausnitz MR. Coated microneedles for transdermal delivery. J Control Release. 2007;117(2):227–237. [PMC free article] [PubMed] [Google Scholar]

42. Lanke SSS, Kolli CS, Strom JG, Banga AK. Enhanced transdermal delivery of low molecular weight heparin by barrier perturbation. Int J Pharm. 2009;365(1–2):26–33. [PubMed] [Google Scholar]

43. Wermeling DP, Banks SL, Hudson DA, et al. Microneedles permit transdermal delivery of a skin-impermeant medication to humans. Proc Natl Acad Sci USA. 2008;105(6):2058–2063. [PMC free article] [PubMed] [Google Scholar]

44. Riviere JE, Heit MC. Electrically-assisted transdermal drug delivery. Pharm Res. 1997;14(6):687–697. [PubMed] [Google Scholar]

45. Warwick WJ, Huang NN, Waring WW, et al. Evaluation of a cystic fibrosis screening system incorporating a miniature sweat stimulator and disposable chloride sensor. Clin Chem. 1986;32(5):850–853. [PubMed] [Google Scholar]

46. Squire SJ, Kirchhoff KT, Hissong K. Comparing two methods of topical anesthesia used before intravenous cannulation in pediatric patients. J Pediatr Healthcare. 2000;14(2):68–72. [PubMed] [Google Scholar]

47. Patel SR, Zhong H, Sharma A, Kalia YN. Controlled non-invasive transdermal iontophoretic delivery of zolmitriptan hydrochloride in vitro and in vivo. Eur J Pharm Biopharm. 2009;72(2):304–309. [PubMed] [Google Scholar]

48. Nakamura K, Katagai K, Mori K, Higo N, Sato S, Yamamoto K. Transdermal administration of salmon calcitonin by pulse depolarization-iontophoresis in rats. Int J Pharm. 2001;218(1–2):93–102. [PubMed] [Google Scholar]

49. Pillai O, Panchagnula R. Transdermal delivery of insulin from poloxamer gel: ex vivo and in vivo skin permeation studies in rat using iontophoresis and chemical enhancers. J Control Release. 2003;89(1):127–140. [PubMed] [Google Scholar]

50. Rastogi SK, Singh J. Transepidermal transport enhancement of insulin by lipid extraction and iontophoresis. Pharm Res. 2002;19(4):427–433. [PubMed] [Google Scholar]

51. Suzuki Y, Nagase Y, Iga K, et al. Prevention of bone loss in ovariectomized rats by pulsatile transdermal iontophoretic administration of 91(2), human PTH1–34. J Pharm Sci. 2002:350–361. [PubMed] [Google Scholar]

52. Nair V, Panchagnula R. Physicochemical considerations in the iontophoretic delivery of a small peptide: in vitro studies using arginine vasopressin as a model peptide. Pharmacol Res. 2003;48(2):175–182. [PubMed] [Google Scholar]

53. Galinkin JL, Rose JB, Harris K, Watcha MF. Lidocaine iontophoresis versus eutectic mixture of local anesthetics (EMLA®) for IV placement in children. Anesth Analg. 2002;94(6):1484–1488. [PubMed] [Google Scholar]

54. Runeson L, Haker E. Iontophoresis with cortisone in the treatment of lateral epicondylalgia (tennis elbow) – a double-blind study. Scand J Med Sci Sports. 2002;12(3):136–142. [PubMed] [Google Scholar]

55. Gupta SK, Bernstein KJ, Noorduin H, Van Peer A, Sathyan G, Haak R. Fentanyl delivery from an electrotransport system: delivery is a function of total current, not duration of current. J Clin Pharmacol. 1998;38(10):951–958. [PubMed] [Google Scholar]

56. Singh J, Gross M, Sage B, Davis HT, Maibach HI. Regional variations in skin barrier function and cutaneous irritation due to iontophoresis in human subjects. Food Chem Toxicol. 2001;39(11):1079–1086. [PubMed] [Google Scholar]

57. Prausnitz MR. A practical assessment of transdermal drug delivery by skin electroporation. Adv Drug Deliv Rev. 1999;35(1):61–76. [PubMed] [Google Scholar]

58. Denet AR, Preat V. Transdermal delivery of timolol by electroporation through human skin. J Control Release. 2003;88(2):253–262. [PubMed] [Google Scholar]

59. Zewert TE, Pliquett UF, Vanbever R, Langer R, Weaver JC. Creation of transdermal pathways for macromolecule transport by skin electroporation and a low toxicity, pathway-enlarging molecule. Bioelectrochem Bioenerg. 1999;49(1):11–20. [PubMed] [Google Scholar]

60. Mitragotri S. Effect of therapeutic ultrasound on partition and diffusion coefficients in human stratum corneum. J Control Release. 2001;71(1):23–29. [PubMed] [Google Scholar]

61. Tang H, Wang CCJ, Blankschtein D, Langer R. An investigation of the role of cavitation in low-frequency ultrasound-mediated transdermal drug transport. Pharm Res. 2002;19(8):1160–1169. [PubMed] [Google Scholar]

62. Mitragotri S, Blankschtein D, Langer R. Transdermal drug delivery using low-frequency sonophoresis. Pharm Res. 1996;13(3):411–420. [PubMed] [Google Scholar]

63. Mitragotri S, Blankschtein D, Langer R. Ultrasound-mediated transdermal protein delivery. Science. 1995;269(5225):850–853. [PubMed] [Google Scholar]

64. Mitragotri S, Edwards DA, Blankschtein D, Langer R. Mechanistic study of ultrasonically-enhanced transdermal drug-delivery. J Pharm Sci. 1995;84(6):697–706. [PubMed] [Google Scholar]

65. Mitragotri S, Farrell J, Tang H, Terahara T, Kost J, Langer R. Determination of threshold energy dose for ultrasound-induced transdermal drug transport. J Control Release. 2000;63(1–2):41–52. [PubMed] [Google Scholar]

66▪. Cross SE, Roberts MS. Physical enhancement of transdermal drug application: is delivery technology keeping up with pharmaceutical development? Curr Drug Delivery. 2004;1(1):81–92. Extensive review of the physical enhancement methods used in percutaneous drug delivery. [PubMed] [Google Scholar]

67. Kost J, Pliquett U, Mitragotri S, Yamamoto A, Langer R, Weaver J. Synergistic effect of electric field and ultrasound on transdermal transport. Pharm Res. 1996;13(4):633–638. [PubMed] [Google Scholar]

68. Riviere JE, Monteiroriviere NA, Rogers RA, Bommannan D, Tamada JA, Potts RO. Pulsatile transdermal delivery of LHRH using electroporation: drug delivery and skin toxicology. J Control Release. 1995;36(3):229–233. [Google Scholar]

69. Chang SL, Hofmann GA, Zhang L, Deftos LJ, Banga AK. The effect of electroporation on iontophoretic transdermal delivery of calcium regulating hormones. J Control Release. 2000;66(2–3):127–133. [PubMed] [Google Scholar]

70. Prausnitz MR. Microneedles for transdermal drug delivery. Adv Drug Deliv Rev. 2004;56 (5):581–587. [PubMed] [Google Scholar]

71. Chen H, Zhu H, Zheng J, et al. Iontophoresis-driven penetration of nanovesicles through microneedle-induced skin microchannels for enhancing transdermal delivery of insulin. J Control Release. 2009;139(1):63–72. [PubMed] [Google Scholar]

72▪. Kasting GB, Smith RL, Anderson BD. In: Prodrugs: Topical and Ocular Drug Delivery. Sloan KB, editor. Marcel Dekker; NY, USA: 1992. pp. 117–161. Discussion of prodrug design for transdermal delivery. [Google Scholar]

73. Qandil A, Al-Nabulsi S, Al-Taani B, Tashtoush B. Synthesis of piperazinylalkyl ester prodrugs of ketorolac and their in vitro evaluation for transdermal delivery. Drug Dev Ind Pharm. 2008;34(10):1054–1063. [PubMed] [Google Scholar]

74. Kushnir M, Yaar A, Reichman A, Heldman E. Transdermal delivery of a levodopa prodrug; a pilot clinical trial. Mov Disord. 2008;23:592. [Google Scholar]

75. Thomas JD, Majumdar S, Sloan KB. Soft alkyl ether prodrugs of a model phenolic drug: the effect of incorporation of ethyleneoxy groups on transdermal delivery. Molecules. 2009;14(10):4231–4245. [PMC free article] [PubMed] [Google Scholar]

76. Strasinger CL, Scheff NN, Stinchcomb AL. Prodrugs and codrugs as strategies for improving percutaneous absorption. Expert Rev Dermatol. 2008;3(2):221–233. [Google Scholar]

77. Vaddi HK, Banks SL, Chen J, Hammell DC, Crooks PA, Stinchcomb AL. Human skin permeation of 3-O-alkyl carbamate prodrugs of naltrexone. J Pharm Sci. 2009;98(8):2611–2625. [PMC free article] [PubMed] [Google Scholar]

78. Kiptoo PK, Paudel KS, Hammell DC, et al. Transdermal delivery of bupropion and its active metabolite, hydroxybupropion: a prodrug strategy as an alternative approach. J Pharm Sci. 2009;98(2):583–594. [PMC free article] [PubMed] [Google Scholar]

79▪. Murphy M, Carmichael AJ. Transdermal drug delivery systems and skin sensitivity reactions: incidence and management. Am J Clin Dermatol. 2000;1(6):361–368. Discusses characteristics, sources, management and prevention of skin irritation reactions caused by drug delivery systems. [PubMed] [Google Scholar]

80. Berner B, Wilson DR, Guy RH, Mazzenga GC, Clarke FH, Maibach HI. The relationship of pka and acute skin irritation in man. Pharm Res. 1988;5(10):660–663. [PubMed] [Google Scholar]

81. Berner BWD, Steffens RJ, Mazzenga GC, Hinz R, Guy RH, Maibach HI. The relationship between pka and skin irritation for a series of basic penetrants in man. Fundam Appl Toxicol. 1990;15(4):760–766. [PubMed] [Google Scholar]

82. Andersen PH, Nangia A, Bjerring P, Maibach HI. Chemical and pharmacologic skin irritation in man. Contact Derm. 1991;25(5):283–289. [PubMed] [Google Scholar]

83. Mangia A, Andersen PH, Berner B, Maibach HI. High dissociation constants (pKa) of basic permeants are associated with in vivo skin irritation in man. Contact Derm. 1996;34(4):237–242. [PubMed] [Google Scholar]

84. Johnson W. Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin. Int J Toxicol. 2007;26(Suppl 1):3–106. [PubMed] [Google Scholar]

85. Branco N, Lee I, Hongbo Z, Maibach HI. Long-term repetitive sodium lauryl sulfate-induced irritation of the skin: an in vivo study. Contact Derm. 2005;53(5):278–284. [PubMed] [Google Scholar]

86▪. Fluhr JW, Darlenski R, Angelova-Fischer I, Tsankov N, Basketter D. Skin irritation and sensitization: mechanisms and new approaches for risk assessment. Skin Pharmacol Physiol. 2008;21(3):124–135. Discusses skin irritation and sensitization in detail as well as current methods used to determine their presence and extent. [PubMed] [Google Scholar]

87. Fang JY, Tsai MJ, Huang YB, Wu PC, Tsai YH. Percutaneous absorption and skin erythema: quantification of capsaicin and its synthetic derivatives from gels incorporated with benzalkonium chloride by using non-invasive bioengineering methods. Drug Dev Res. 1997;40(1):56–67. [Google Scholar]

88. Schmid-Wendtner MH, Korting HC. The pH of the skin surface and its impact on the barrier function. Skin Pharmacol Physiol. 2006;19(6):296–302. [PubMed] [Google Scholar]

89. Antoine JL, Contreras JL, Van Neste DJ. pH influence of surfactant-induced skin irritation. Derm Beruf Umwelt. 1989;37(3):96–100. [PubMed] [Google Scholar]

90. Ananthapadmanabhan KP, Lips A, Vincent C, et al. pH-induced alterations in stratum corneum properties. Int J Cosmetic Sci. 2003;25(3):103–112. [PubMed] [Google Scholar]

91. Williams A. Pharmaceutical solvents as vehicles for topical dosage forms. In: Augustijns P, Brewster ME, editors. Solvent Systems and Their Selection in Pharmaceutics and Biopharmaceutics. Vol. 6. Springer; NY, USA: 2007. pp. 403–426. [Google Scholar]

92. Matsumura H, Oka K, Umekage K, et al. Effect of occlusion on human skin. Contact Derm. 1995;33(4):231–235. [PubMed] [Google Scholar]

93. Homick JLKR, Reschke MF, Degioanni J, Cintron-Trevino NM. Transdermal scopolamine in the prevention of motion sickness: evaluation of the time course of efficacy. Aviat Space Environ Med. 1983;54(11):994–1000. [PubMed] [Google Scholar]

94. Hurkmans JF, Bodde HE, Driel LM, Doorne HV, Junginger HE. Skin irritation caused by transdermal drug delivery systems during long-term (5 days) application. Br J Dermatol. 1985;112(4):461–467. [PubMed] [Google Scholar]

95. Van der Valk PG, Maibach HI. Post-application occlusion substantially increases the irritant response of the skin to repeated short-term sodium lauryl sulfate (SLS) exposure. Contact Derm. 1989;21(5):335–338. [PubMed] [Google Scholar]

96. Tsen-Fang T, Maibach HI. How irritant is water? An overview. Contact Derm. 1999;41(6):311–314. [PubMed] [Google Scholar]

97. Dwyer CM, Forsyth A. Allergic contact dermatitis from methacrylates in a nicotine transdermal patch. Contact Derm. 1994;30(5):309–310. [PubMed] [Google Scholar]

98. Ross D, Rees M, Godfree V, et al. Randomised crossover comparison of skin irritation with two transdermal oestradiol patches. BMJ. 1997;315(7103):288. [PMC free article] [PubMed] [Google Scholar]

99. Marier JF, Lor M, Potvin D, Dimarco M, Morelli G, Saedder EA. Pharmacokinetics, tolerability, and performance of a novel matrix transdermal delivery system of fentanyl relative to the commercially available reservoir formulation in healthy subjects. J Clin Pharmacol. 2006;46(6):642–653. [PubMed] [Google Scholar]

100. Wester RC, Patel R, Nacht S, Leyden J, Melendres J, Maibach H. Controlled release of benzoyl peroxide from a porous microsphere polymeric system can reduce topical irritancy. J Am Acad Dermatol. 1991;24(5 Pt 1):720–726. [PubMed] [Google Scholar]

101▪. de Leeuw J, de Vijlder HC, Bjerring P, Neumann HAM. Liposomes in dermatology today. J Eur Acad Dermatol. 2009;23(5):505–516. Discusses the characteristics of liposome formulations, a synopsis of the state of liposome research and how liposomal formulations are impacting the field of dermal drug delivery. [PubMed] [Google Scholar]

102. Schäfer-Korting M, Korting HC, Ponce-Pöschl E. Liposomal tretinoin for uncomplicated acne vulgaris. Clin Invest. 1994;72(12):1086–1091. [PubMed] [Google Scholar]

103. Zhai H, Willard P, Maibach HI. Evaluating skin-protective materials against contact irritants and allergens. Contact Derm. 1998;38(3):155–158. [PubMed] [Google Scholar]

104. Wigger-Alberti W, Hinnen U, Elsner P. Predictive testing of metalworking fluids: a comparison of 2 cumulative human irritation models and correlation with epidemiological data. Contact Derm. 1997;6(1):14–20. [PubMed] [Google Scholar]

105. Ben-Shabat S, Baruch N, Sintov AC. Conjugates of unsaturated fatty acids with propylene glycol as potentially less-irritant skin penetration enhancers. Drug Dev Ind Pharm. 2007;33(11):1169–1175. [PubMed] [Google Scholar]

106. Sintov A, Ben-Shabat S. Design of fatty acid conjugates for dermal delivery and topical therapeutics. Anglais. 2006;23(1):67–87. [PubMed] [Google Scholar]

107. Karande P, Mitragotri S. Enhancement of transdermal drug delivery via synergistic action of chemicals. Biochim Biophys Acta Biomembranes. 2009;1788(11):2362–2373. [PubMed] [Google Scholar]

108. Wilson DE, Kaidbey K, Boike SC, Jorkasky DK. Use of topical corticosteroid pretreatment to reduce the incidence and severity of skin reactions associated with testosterone transdermal therapy. Clin Ther. 1998;20(2):299–306. [PubMed] [Google Scholar]

109. Amkraut AA, Jordan WP, Taskovich L. Effect of coadministration of corticosteroids on the development of contact sensitization. J Am Acad Dermatol. 1996;35(1):27–31. [PubMed] [Google Scholar]

110. Andersen F, Hedegaard K, Petersen TK, Bindslev-Jensen C, Fullerton A, Andersen KE. Anti-irritants I: Dose-response in acute irritation. Contact Derm. 2006;55(3):148–154. [PubMed] [Google Scholar]

111. Andersen F, Hedegaard K, Petersen TK, Bindslev-Jensen C, Fullerton A, Andersen KE. Comparison of the effect of glycerol and triamcinolone acetonide on cumulative skin irritation in a randomized trial. J Am Acad Dermatol. 2007;56(2):228–235. [PubMed] [Google Scholar]

112. Huang YB, Tsai YH, Chang JS, Liu JC, Tsai MJ, Wu PC. Effect of antioxidants and anti-irritants on the stability, skin irritation and penetration capacity of captopril gel. Int J Pharm. 2002;241(2):345–351. [PubMed] [Google Scholar]

Page 2

List of transdermal products currently on the US market.

Active ingredients	Type of delivery system	Name	Company	Type of patch	Dose and application	Regulatory status	Uses
Clonidine	Transdermal patch extended release	Catapres TTS®	Boehringer Ingelheim	Drug in reservoir and in adhesive formulation	3.5–10.5-cm2 patches deliver0.1–0.3 mg/day for 7 days Applied to hairless skin on the upper outer arm or chest	Rx	Essential hypertension
Clonidine	Par Pharm	Reservoir type	0.1–0.3 mg/24 h for 7 days
Estradiol	Transdermal patch extended release	Alora®	Watson Laboratories	Adhesive matrix drug reservoir	9–36-cm2 patches deliver0.025–0.1 mg/day and continuous delivery for twice weekly dosing Applied to lower abdomen	Rx	Menopause, postmenopausal and osteoporosis, in case of lowered estrogen levels
Climara®	Bayer Healthcare	Adhesive matrix containing drug	6.5–25-cm2 patches deliver0.025–0.1 mg/day for 7 days Applied to lower abdomen or upper quadrant of buttock
Estraderm®	Novartis	Reservoir type	0.05 or 0.1-mg/day and continuous delivery for twice weekly application
Estradiol	Mylan Technologies	Adhesive matrix containing drug	0.025–0.1 mg/day continuous delivery once weekly patch
Menostar®	Bayer Healthcare	Adhesive matrix containing drug	3.25-cm2 delivers 14 μg/day for 7 days Applied near lower abdomen
Vivelle®/Vivelle-Dot	Novartis/Novogyne	Adhesive formulation contains drug	Patches having active surface area of 2.5–10 cm2 deliver 0.025–0.1 mg/day and twice weekly application Applied to the abdomen
Transdermal gel	Divigel®	Upsher-Smith Laboratories	0.1% gel	0.25–1 g dose available Applied to a small area (200 cm2) of the thigh in a thin, quick-drying layer
Elestrin®	Azur Pharma	0.06% gel supplied in a non-aerosol, metered-dose pump container	Applied once daily to the upper arm using a metered-dose pump that delivers 0.87 g of Elestrin® gel per actuation
Estrogel®	Ascend Therapeutics	0.06% estradiol in an absorptive hydroalcoholic gel	1.25 g in a single dose and applied to 750-cm2 area Applied to arm between wrist and shoulder
Transdermal spray	Evamist™	KV Pharm/Ther-Rx	Topical application to the skin of a rapidly drying homogeneous solution of 1.7% drug from a metered-dose pump	One, two or three sprays/day (90 μl/spray) to adjacent nonoverlapping 20-cm2 areas on the inner surface of the arm between the elbow and the wrist and allowed to dry	Rx	Menopause, postmenopausal and osteoporosis, in case of lowered estrogen levels
Estradiol and levonorgestrel	Transdermal patch extended release	Climara Pro™	Bayer Healthcare Pharmaceuticals	Drug in adhesive layer	22-cm2 Climara Pro™ system contains 4.4 mg estradiol and 1.39 mg levonorgestrel and delivers 0.045 mg estradiol and 0.015 mg levonorgestrel/day for 7 days applied to lower abdomen	Rx	Menopausal symptoms
Estradiol and norethindrone acetate	Transdermal patch extended release	Combipatch®	Novartis	Adhesive layer contains both drugs	9–16-cm2 patches deliver 0.05/0.14 or 0.05/0.25 mg estradiol/norethindrone acetate per day and applied twice weekly to lower abdomen	Rx	Menopausal symptoms
Ethinyl estradiol and norelgestromin	Transdermal patch extended release	Ortho Evra®	Ortho McNeil Janssen	Adhesive matrix containing drug	6.00 mg norelgestromin and 0.75 mg ethinyl estradiol in each 20-cm2 patch and delivers for 7 days Applied to buttock, abdomen, upper outer arm or upper torso	Rx	Contraception
Fentanyl	Transdermal patch extended release	Fentanyl transdermal system	Actavis, Mylan Technologies, Lavipharm Labs, Noven, Watson Laboratories and Teva Pharms	Matrix type (Mylan technologies and Teva Pharms) and reservoir (Actavis and Watson laboratories)	10–40-cm2 patches deliver 25–100 μg/h	Schedule II	Chronic pain (opioid tolerant) that cannot be managed by any other means
Duragesic®	Ortho McNeil Janssen	Drug in reservoir and in adhesive formulation	5–40-cm2 patches deliver 12.5–100 μg/h continuous systemic delivery for 72 h applied to flat surface such as the chest, back, flank or upper arm
Granisetron	Transdermal patch extended release	Sancuso®	Prostraken	Adhesive matrix containing drug	52-cm2 patch containing 34.3 mg of granisetron. The patch releases 3.1 mg of granisetron per 24 h for up to 7 days Applied to upper outer arm	Rx	Chemotherapy-induced nausea and vomiting
Methylphenidate	Transdermal patch extended release	Daytrana®	Shire	Adhesive-based matrix type patch	12.5–37.5-cm2 patches deliver 10–30 mg/9 h per patch applied to the hip area 2 h before an effect is needed and should be removed 9 h after application	Schedule II	Attention-deficit hyperactivity disorder
Nicotine	Transdermal patch extended release	Nicoderm® CQ	Aventis	Matrix type patch	7–21 mg over 24 h at different stages of the treatment	OTC	Smoking cessation
Nicotine transdermal system	Novartis Consumer, Watson Laboratories, Cardinal Health and Aveva	Matrix type patch	7–21 mg/24 h at different stages of treatment
Habitrol®	Novartis and Novartis Consumer	Reservoir type	17.5–52.5 mg that delivers 7–21 mg/day for the duration of treatment
Nitroglycerin	Transdermal patch extended release	Nitro Dur®	Key Pharmaceuticals	Drug in adhesive	5–40-cm2 patch delivers 0.1–0.8 mg/h for 12–14 h	Rx	Angina prophylaxis
Nitroglycerin	Noven, Hercon Laboratories, Kremers Urban and Mylan Technologies	Drug in adhesive	Delivers nitroglycerin at 0.2 mg/h
Minitran Transdermal System™	Graceway Pharmaceuticals	Drug in adhesive	Delivers 0.1–0.6 mg/h
Transdermal ointment	Nitroglycerin	Fougera	2%	7.5–30 mg applied in the morning and again 6 h later to a 36-inch2 area of truncal skin
Oxybutynin	Transdermal patch extended release	Oxytrol®	Watson Laboratories	Adhesive matrix containing drug	39 cm2 system containing 36 mg and has a nominal in vivo delivery rate of 3.9 mg oxybutynin per day consistently for 3–4 days Applied to abdomen, hip or buttock	Rx	Bladder muscle dysfunction
Oxybutynin chloride	Transdermal gel	Gelnique®	Watson Labs	10% gel	100 mg applied once daily to dry, intact skin on the abdomen, upper arms/shoulders or thighs (area of application rotated)	Rx	Bladder muscle dysfunction
Rivastigmine	Transdermal patch extended release	Exelon®	Novartis	Matrix reservoir containing drug	4.6–9.5 mg/24 h from 5–10-cm2 patches Preferable application to upper or lower back	Rx	Dementia associated with Alzheimer’s disease and Parkinson’s disease
Scopolamine	Transdermal patch extended release	Transderm Scop®	Novartis	Matrix reservoir containing drug	2.5-cm2 patch delivers 1.0 mg for 3 days Applied to the hairless area behind one ear	Rx	Motion sickness, Postoperative nausea and vomiting (prophylaxis).
Selegiline	Transdermal patch extended release	Emsam®	Somerset	Drug in adhesive	6–12 mg/24 h from 20–40-cm2 patch Applied to the upper torso, upper thigh or the outer surface of the upper arm	Rx	Major depressive disorder
Testosterone	Transdermal patch extended release	Androderm®	Watson Laboratories and Watson Pharma	Reservoir type	2.5 or 5 mg/day from 37–44-cm2 patch	Schedule III Rx	Hypogonadism (testosterone deficiency)
Transdermal gel	Androgel®	Unimed Pharma and Solvay/Abbott	1% gel	5–10 g contains 50–100 mg, 10% of the applied testosterone dose is absorbed across skin of average permeability during a 24-h period Applied 5 g once daily to shoulders and upper arms and/or abdomen