Transdermal Drug Therapy: Emerging Techniques and Improved Patient Compliance

  • Avinash Kumar Seth


Transdermal drug therapy has made a breakthrough over the past few years amid emerging technologies and strategies for repositioning of drugs to deliver through the skin: a strong barrier. In spite of various benefits of transdermal routes of drug delivery such as avoidance of first-pass metabolism, easy mode of application, high patient compliance, and controlled release of medication, researchers today are facing numerous challenges in order for patients and clinicians to embrace transdermal drug delivery system (TDDS). One of the key impediments facing TDDS is the narrow range of drug positioning as a result of the skin being a strong barrier for drugs with molecular weight > 500 Da and its hydrophilic nature. To overcome these challenges, immense research work was carried out to extend the scope of TDDS to incorporate wide range of drug molecules which may include high molecular weight drugs, especially biotechnologically developed macromolecules and vaccines. Moreover, extensive research was undertaken by scientists in developing new transdermal technologies to deliver wide range of drugs to treat various chronic diseases. The quantum of research work is demonstrated by many patents filed and granted to industries and academic institutions. This chapter discusses about the basics of transdermal permeation mechanisms considering physiochemical characteristics of drug molecules and drug delivery systems. Furthermore, it focuses on emerging technologies for skin permeation enhancement that has led to high patient compliance. Besides, it also illustrates on the current available TDDS in the market with narrow range of drugs; however, ongoing clinical trials and new technologies suggest that there is a great future of TDDS in repositioning wider range of drugs bypassing the existing patents.


TDDS Stratum corneum Transcellular route Transdermal patch Electroporation Inontophoresis Thermal ablation Microneedle array 


  1. 1.
    Kumar JA, Pullakandam N, Prabu SL, Gopal V (2010) Transdermal drug delivery system: an overview. Int J Pharm Sci Rev Res 3(2):49–54Google Scholar
  2. 2.
    Sugibayashi K, Morimoto Y (1994) Polymers for transdermal drug delivery systems. J Control Release 29(1):177–185CrossRefGoogle Scholar
  3. 3.
    Arora A, Prausnitz MR, Mitragotri S (2008) Micro-scale devices for transdermal drug delivery. Int J Pharm 364(2):227–236. Epub 2008/09/23PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Banga AK (2011) Transdermal and intradermal delivery of therapeutic agents: application of physical technologies. CRC Press, Boca RatonCrossRefGoogle Scholar
  5. 5.
    Elias PM, Menon GK (1991) Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 24:1–26. Epub 1991/01/01PubMedCrossRefGoogle Scholar
  6. 6.
    Ng KW, Lau WM (2015) Skin deep: the basics of human skin structure and drug penetration. In: Dragicevic N, Maibach HI (eds) Percutaneous penetration enhancers chemical methods in penetration enhancement: drug manipulation strategies and vehicle effects. Springer, Berlin/Heidelberg, pp 3–11Google Scholar
  7. 7.
    Brouaugh RL, Maibach HI (1989) Percutaneous absorptions, 2nd edn. Marcel Dekker Inc, New YorkGoogle Scholar
  8. 8.
    Bhowmick M, Sengodan T, Thangavel S (2012) Challenges Facing Transdermal Drug Delivery Systems: A Conceptual Approach. Res J Sci Technol 4(5):197–200Google Scholar
  9. 9.
    Keleb E, Sharma RK, Mosa EB, Aljahwi A-AZ (2010) Transdermal drug delivery system-design and evaluation. Int J Adv Pharm Sci 1(3):201–211Google Scholar
  10. 10.
    Naik A, Kalia YN, Guy RH (2000) Transdermal drug delivery: overcoming the skin’s barrier function. Pharm Sci Technol Today 3(9):318–326PubMedCrossRefGoogle Scholar
  11. 11.
    Patel RP, Baria AH (2011) Formulation and evaluation considerations of transdermal drug delivery system. Int J Pharm Res 3(1):1–9Google Scholar
  12. 12.
    McCrudden MT, Alkilani AZ, McCrudden CM, McAlister E, McCarthy HO, Michael WH (2014) Future of transdermal drug delivery systems. Am Pharm Rev (TDDS) [cited 2014 19th June]Google Scholar
  13. 13.
    Anselmo AC, Mitragotri S (2014) An overview of clinical and commercial impact of drug delivery systems. J Control Release 190:15–28. Epub 2014/04/22PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Choy YB, Prausnitz MR (2011) The rule of five for non-oral routes of drug delivery: ophthalmic, inhalation and transdermal. Pharm Res 28(5):943–948. Epub 2010/10/23PubMedCrossRefGoogle Scholar
  15. 15.
    Wiedersberg S, Guy RH (2014) Transdermal drug delivery: 30+ years of war and still fighting! J Control Release 190:150–156. Epub 2014/05/24PubMedCrossRefGoogle Scholar
  16. 16.
    Donnelly RF, Raj Singh TR, Woolfson AD (2010) Microneedle-based drug delivery systems: microfabrication, drug delivery, and safety. Drug Deliv 17(4):187–207. Epub 2010/03/20PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Kalia YN, Guy RH (2001) Modeling transdermal drug release. Adv Drug Deliv Rev 48(2–3):159–172. Epub 2001/05/23PubMedCrossRefGoogle Scholar
  18. 18.
    Moser K, Kriwet K, Naik A, Kalia YN, Guy RH (2001) Passive skin penetration enhancement and its quantification in vitro. Eur J Pharm Biopharm 52(2):103–112PubMedCrossRefGoogle Scholar
  19. 19.
    Williams AC, Barry BW (2012) Penetration enhancers. Adv Drug Deliv Rev 64:128–137CrossRefGoogle Scholar
  20. 20.
    Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2012) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 64:4–17CrossRefGoogle Scholar
  21. 21.
    Park JH, Allen MG, Prausnitz MR (2005) Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J Control Release 104(1):51–66. Epub 2005/05/04PubMedCrossRefGoogle Scholar
  22. 22.
    Schoellhammer CM, Blankschtein D, Langer R (2014) Skin permeabilization for transdermal drug delivery: recent advances and future prospects. Expert Opin Drug Deliv 11(3):393–407. Epub 2014/01/08PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Brambilla D, Luciani P, Leroux J-C (2014) Breakthrough discoveries in drug delivery technologies: the next 30 years. J Control Release 190:9–14PubMedCrossRefGoogle Scholar
  24. 24.
    El Maghraby GM, Williams AC, Barry BW (2006) Can drug-bearing liposomes penetrate intact skin? J Pharm Pharmacol 58(4):415–429. Epub 2006/04/07PubMedCrossRefGoogle Scholar
  25. 25.
    Schuetz YB, Naik A, Guy RH, Kalia YN (2005) Emerging strategies for the transdermal delivery of peptide and protein drugs. Expert Opin Drug Deliv 2(3):533–548. Epub 2005/11/22PubMedCrossRefGoogle Scholar
  26. 26.
    Rehman K, Zulfakar MH (2014) Recent advances in gel technologies for topical and transdermal drug delivery. Drug Dev Ind Pharm 40(4):433–440. Epub 2013/08/14PubMedCrossRefGoogle Scholar
  27. 27.
    Paudel KS, Milewski M, Swadley CL, Brogden NK, Ghosh P, Stinchcomb AL (2010) Challenges and opportunities in dermal/transdermal delivery. Ther Deliv 1(1):109–131PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Karande P, Mitragotri S (2009) Enhancement of transdermal drug delivery via synergistic action of chemicals. Biochim Biophys Acta 1788(11):2362–2373. Epub 2009/09/08PubMedCrossRefGoogle Scholar
  29. 29.
    Mitragotri S (2013) Devices for overcoming biological barriers: the use of physical forces to disrupt the barriers. Adv Drug Deliv Rev 65(1):100–103. Epub 2012/09/11PubMedCrossRefGoogle Scholar
  30. 30.
    Azagury A, Khoury L, Enden G, Kost J (2014) Ultrasound mediated transdermal drug delivery. Adv Drug Deliv Rev 72:127–143. Epub 2014/01/28PubMedCrossRefGoogle Scholar
  31. 31.
    Han T, Das DB (2015) Potential of combined ultrasound and microneedles for enhanced transdermal drug permeation: a review. Eur J Pharm Biopharm 89:312–328. Epub 2014/12/30PubMedCrossRefGoogle Scholar
  32. 32.
    Lee JW, Gadiraju P, Park JH, Allen MG, Prausnitz MR (2011) Microsecond thermal ablation of skin for transdermal drug delivery. J Control Release 154(1):58–68. Epub 2011/05/21PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Zhang D, Rielly CD, Das DB (2015) Microneedle-assisted microparticle delivery by gene guns: experiments and modeling on the effects of particle characteristics. Drug Deliv 22(3):335–350PubMedCrossRefGoogle Scholar
  34. 34.
    Skauen DM, Zentner GM (1984) Phonophoresis. Int J Pharm 20(3):235–245CrossRefGoogle Scholar
  35. 35.
    Polat BE, Hart D, Langer R, Blankschtein D (2011) Ultrasound-mediated transdermal drug delivery: mechanisms, scope, and emerging trends. J Control Release 152(3):330–348. Epub 2011/01/18PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Singer AJ, Homan CS, Church AL, McClain SA (1998) Low-frequency sonophoresis: pathologic and thermal effects in dogs. Acad Emerg Med 5(1):35–40PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Ita K (2014) Transdermal drug delivery: progress and challenges. J Drug Deliv Sci Technol 24(3):245–250CrossRefGoogle Scholar
  38. 38.
    Neumann E, Schaefer-Ridder M, Wang Y, Hofschneider PH (1982) Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J 1(7):841–845PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Adamo A, Roushdy O, Dokov R, Sharei A, Jensen KF (2013) Microfluidic jet injection for delivering macromolecules into cells. J Micromech Microeng 23(3):035026PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Denet AR, Preat V (2003) Transdermal delivery of timolol by electroporation through human skin. J Control Release 88(2):253–262. Epub 2003/03/12PubMedCrossRefGoogle Scholar
  41. 41.
    Preat V, Vanbever R (2003) Skin electroporation for transdermal and topical drug delivery. Drugs Pharm Sci 123:227–254Google Scholar
  42. 42.
    Prausnitz MR, Bose VG, Langer R, Weaver JC (1993) Electroporation of mammalian skin: a mechanism to enhance transdermal drug delivery. Proc Natl Acad Sci 90(22):10504–10508PubMedCrossRefGoogle Scholar
  43. 43.
    Bommannan DB, Tamada J, Leung L, Potts RO (1994) Effect of electroporation on transdermal iontophoretic delivery of luteinizing hormone releasing hormone (LHRH) in vitro. Pharm Res 11(12):1809–1814. Epub 1994/12/01PubMedCrossRefGoogle Scholar
  44. 44.
    Chang SL, Hofmann GA, Zhang L, Deftos LJ, Banga AK (2000) The effect of electroporation on iontophoretic transdermal delivery of calcium regulating hormones. J Control Release 66(2–3):127–133. Epub 2000/04/01PubMedCrossRefGoogle Scholar
  45. 45.
    Lakshmanan S, Gupta GK, Avci P, Chandran R, Sadasivam M, Jorge AE et al (2014) Physical energy for drug delivery; poration, concentration and activation. Adv Drug Deliv Rev 71:98–114. Epub 2013/06/12PubMedCrossRefGoogle Scholar
  46. 46.
    Lombry C, Dujardin N, Préat V (2000) Transdermal delivery of macromolecules using skin electroporation. Pharm Res 17(1):32–37PubMedCrossRefGoogle Scholar
  47. 47.
    Prausnitz MR, Edelman ER, Gimm JA, Langer R, Weaver JC (1995) Transdermal Delivery of Heparin by Skin Electroporation. Bio/Technology 13:1205PubMedGoogle Scholar
  48. 48.
    Yi J, Barrow AJ, Yu N, O’Neill BE (2013) Efficient electroporation of liposomes doped with pore stabilizing nisin. J liposome Res 23(3):197–202. Epub 2013/04/19PubMedCrossRefGoogle Scholar
  49. 49.
    Badkar AV, Banga AK (2002) Electrically enhanced transdermal delivery of a macromolecule. J Pharm Pharmacol 54(7):907–912. Epub 2002/08/07PubMedCrossRefGoogle Scholar
  50. 50.
    Gratieri T, Alberti I, Lapteva M, Kalia YN (2013) Next generation intra- and transdermal therapeutic systems: using non- and minimally-invasive technologies to increase drug delivery into and across the skin. Eur J Pharm Sci 50(5):609–622. Epub 2013/04/10PubMedCrossRefGoogle Scholar
  51. 51.
    McCrudden MT, Alkilani AZ, McCrudden CM, McAlister E, McCarthy HO, Woolfson AD et al (2014) Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs. J Control Release 180:71–80. Epub 2014/02/22PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Dixit N, Bali V, Baboota S, Ahuja A, Ali J (2007) Iontophoresis – an approach for controlled drug delivery: a review. Curr Drug Deliv 4(1):1–10. Epub 2007/02/03PubMedGoogle Scholar
  53. 53.
    Khan A, Yasir M, Asif M, Chauhan I, Singh AP, Sharma R et al (2011) Iontophoretic drug delivery: history and applications. J Appl Pharm Sci 1(03):11–24Google Scholar
  54. 54.
    Kotzki S, Roustit M, Arnaud C, Godin-Ribuot D, Cracowski JL (2015) Effect of continuous vs pulsed iontophoresis of treprostinil on skin blood flow. Eur J Pharm Sci 72:21–26. Epub 2015/02/26PubMedCrossRefGoogle Scholar
  55. 55.
    Banga AK (1998) Electrically assisted transdermal and topical drug delivery. Taylor & Francis, OxfordGoogle Scholar
  56. 56.
    Roustit M, Gaillard-Bigot F, Blaise S, Stanke-Labesque F, Cracowski C, Seinturier C et al (2014) Cutaneous iontophoresis of treprostinil in systemic sclerosis: a proof-of-concept study. Clin Pharmacol Ther 95(4):439–445. Epub 2014/01/25PubMedCrossRefGoogle Scholar
  57. 57.
    Pillai O, Nair V, Panchagnula R (2004) Transdermal iontophoresis of insulin: IV. Influence of chemical enhancers. Int J Pharm 269(1):109–120PubMedCrossRefGoogle Scholar
  58. 58.
    Cazares-Delgadillo J, Naik A, Ganem-Rondero A, Quintanar-Guerrero D, Kalia YN (2007) Transdermal delivery of cytochrome C--A 12.4 kDa protein--across intact skin by constant-current iontophoresis. Pharm Res 24(7):1360–1368. Epub 2007/04/26PubMedCrossRefGoogle Scholar
  59. 59.
    Dubey S, Kalia YN (2010) Non-invasive iontophoretic delivery of enzymatically active ribonuclease A (13.6 kDa) across intact porcine and human skins. J Control Release 145(3):203–209. Epub 2010/04/29PubMedCrossRefGoogle Scholar
  60. 60.
    Dubey S, Kalia YN (2014) Understanding the poor iontophoretic transport of lysozyme across the skin: when high charge and high electrophoretic mobility are not enough. J Control Release 183:35–42. Epub 2014/03/25PubMedCrossRefGoogle Scholar
  61. 61.
    Dubey S, Perozzo R, Scapozza L, Kalia YN (2011) Noninvasive transdermal iontophoretic delivery of biologically active human basic fibroblast growth factor. Mol Pharm 8(4):1322–1331. Epub 2011/06/24PubMedCrossRefGoogle Scholar
  62. 62.
    LeGrys VA, Yankaskas JR, Quittell LM, Marshall BC, Mogayzel PJ Jr (2007) Diagnostic sweat testing: the Cystic Fibrosis Foundation guidelines. J Pediatr 151(1):85–89. Epub 2007/06/26PubMedCrossRefGoogle Scholar
  63. 63.
    Sun T-P, Shieh H-L, Ching CT-S, Yao Y-D, Huang S-H, Liu C-M et al (2010) Carbon nanotube composites for glucose biosensor incorporated with reverse iontophoresis function for noninvasive glucose monitoring. Int J Nanomed 5:343–349CrossRefGoogle Scholar
  64. 64.
    Krueger E, Claudino Junior JL, Scheeren EM, Neves EB, Mulinari E, Nohama P (2014) Iontophoresis: principles and applications. Fisioterapia em Movimento 27(3):469–481CrossRefGoogle Scholar
  65. 65.
    Mitragotri S (2006) Current status and future prospects of needle-free liquid jet injectors. Nat Rev Drug Discov 5(7):543–548. Epub 2006/07/04PubMedCrossRefGoogle Scholar
  66. 66.
    Stachowiak JC, Li TH, Arora A, Mitragotri S, Fletcher DA (2009) Dynamic control of needle-free jet injection. J Control Release 135(2):104–112. Epub 2009/03/17PubMedCrossRefGoogle Scholar
  67. 67.
    Arora A, Hakim I, Baxter J, Rathnasingham R, Srinivasan R, Fletcher DA et al (2007) Needle-free delivery of macromolecules across the skin by nanoliter-volume pulsed microjets. Proc Natl Acad Sci U S A 104(11):4255–4260. Epub 2007/03/16PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Mitragotri S (2005) Immunization without needles. Nat Rev Immunol 5(12):905–916. Epub 2005/10/22PubMedCrossRefGoogle Scholar
  69. 69.
    Kendall M, Mitchell T, Wrighton-Smith P (2004) Intradermal ballistic delivery of micro-particles into excised human skin for pharmaceutical applications. J Biomech 37(11):1733–1741. Epub 2004/09/25PubMedCrossRefGoogle Scholar
  70. 70.
    Hussain A, Wahab GMKA, ur Rahman MAS, Altaf H, Akhtar N, Qayyum MI (2014) Potential enhancers for transdermal drug delivery: a review. Int J Basic Med Sci Pharm (IJBMSP) 4(1)Google Scholar
  71. 71.
    Donnelly RF, Singh TR, Alkilani AZ, McCrudden MT, O’Neill S, O’Mahony C et al (2013) Hydrogel-forming microneedle arrays exhibit antimicrobial properties: potential for enhanced patient safety. Int J Pharm 451(1–2):76–91. Epub 2013/05/07PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Giannos SA (2014) Skin microporation: strategies to enhance and expand transdermal drug delivery. J Drug Deliv Sci Technol 24(3):293–299CrossRefGoogle Scholar
  73. 73.
    Prausnitz MR, Langer R (2008) Transdermal drug delivery. Nat Biotechnol 26(11):1261–1268. Epub 2008/11/11PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Alexander A, Dwivedi S (2012) Ajazuddin, Giri TK, Saraf S, Saraf S, et al. Approaches for breaking the barriers of drug permeation through transdermal drug delivery. J Control Release 164(1):26–40PubMedCrossRefGoogle Scholar
  75. 75.
    Dhamecha DL, Rajendra V, Rathi A, Ghadlinge S, Saifee M, Dehghan M (2010) Physical approaches to penetration enhancement. Int J Health Res 3(2):57–70Google Scholar
  76. 76.
    Baron ED, Harris L, Redpath WS, Shapiro H, Hetzel F, Morley G et al (2003) Laser-assisted penetration of topical anesthetic in adults. Arch Dermatol 139(10):1288–1290. Epub 2003/10/22PubMedCrossRefGoogle Scholar
  77. 77.
    Lin CH, Aljuffali IA, Fang JY (2014) Lasers as an approach for promoting drug delivery via skin. Expert Opin Drug Deliv 11(4):599–614. Epub 2014/02/05PubMedCrossRefGoogle Scholar
  78. 78.
    Hong X, Wu Z, Chen L, Wu F, Wei L, Yuan W (2014) Hydrogel microneedle arrays for transdermal drug delivery. Nano-Micro Lett 6(3):191–199CrossRefGoogle Scholar
  79. 79.
    Indermun S, Luttge R, Choonara YE, Kumar P, du Toit LC, Modi G et al (2014) Current advances in the fabrication of microneedles for transdermal delivery. J Control Release 185:130–138PubMedCrossRefGoogle Scholar
  80. 80.
    Lademann J, Jacobi U, Surber C, Weigmann HJ, Fluhr JW (2009) The tape stripping procedure – evaluation of some critical parameters. Eur J Pharm Biopharm 72(2):317–323. Epub 2008/09/09PubMedCrossRefGoogle Scholar
  81. 81.
    Escobar-Chavez JJ, Merino-Sanjuan V, Lopez-Cervantes M, Urban-Morlan Z, Pinon-Segundo E, Quintanar-Guerrero D et al (2008) The tape-stripping technique as a method for drug quantification in skin. J Pharm Pharm Sci 11(1):104–130. Epub 2008/05/01PubMedCrossRefGoogle Scholar
  82. 82.
    Tuan-Mahmood TM, McCrudden MT, Torrisi BM, McAlister E, Garland MJ, Singh TR et al (2013) Microneedles for intradermal and transdermal drug delivery. Eur J Pharm Sci 50(5):623–637. Epub 2013/05/18PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Liu S, Jin MN, Quan YS, Kamiyama F, Kusamori K, Katsumi H et al (2014) Transdermal delivery of relatively high molecular weight drugs using novel self-dissolving microneedle arrays fabricated from hyaluronic acid and their characteristics and safety after application to the skin. Eur J Pharm Biopharm 86(2):267–276. Epub 2013/10/15PubMedCrossRefGoogle Scholar
  84. 84.
    Gill HS, Denson DD, Burris BA, Prausnitz MR (2008) Effect of microneedle design on pain in human volunteers. Clin J Pain 24(7):585–594. Epub 2008/08/22PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Ameri M, Kadkhodayan M, Nguyen J, Bravo JA, Su R, Chan K et al (2014) Human growth hormone delivery with a microneedle transdermal system: preclinical formulation, stability, delivery and PK of therapeutically relevant doses. Pharmaceutics 6(2):220–234. Epub 2014/05/20PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    McAllister DV, Wang PM, Davis SP, Park JH, Canatella PJ, Allen MG et al (2003) Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc Natl Acad Sci U S A 100(24):13755–13760. Epub 2003/11/19PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Yung KL, Yan X, Chunlei K, Liu H, Tam KF, Ko SM et al (2012) Sharp tipped plastic hollow microneedle array by microinjection moulding. J Micromech Microeng 22(1):015016CrossRefGoogle Scholar
  88. 88.
    Katsumi H, Liu S, Tanaka Y, Hitomi K, Hayashi R, Hirai Y et al (2012) Development of a novel self-dissolving microneedle array of alendronate, a nitrogen-containing bisphosphonate: evaluation of transdermal absorption, safety, and pharmacological effects after application in rats. J Pharm Sci 101(9):3230–3238. Epub 2012/04/03PubMedCrossRefGoogle Scholar
  89. 89.
    Gomaa YA, Garland MJ, McInnes F, El-Khordagui LK, Wilson C, Donnelly RF (2012) Laser-engineered dissolving microneedles for active transdermal delivery of nadroparin calcium. Eur J Pharm Biopharm 82(2):299–307. Epub 2012/07/28PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Ito Y, Hirono M, Fukushima K, Sugioka N, Takada K (2012) Two-layered dissolving microneedles formulated with intermediate-acting insulin. Int J Pharm 436(1–2):387–393. Epub 2012/07/04PubMedCrossRefGoogle Scholar
  91. 91.
    Kim YC, Park JH, Prausnitz MR (2012) Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev 64(14):1547–1568. Epub 2012/05/12PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Donnelly RF, Moffatt K, Alkilani AZ, Vicente-Perez EM, Barry J, McCrudden MT et al (2014) Hydrogel-forming microneedle arrays can be effectively inserted in skin by self-application: a pilot study centred on pharmacist intervention and a patient information leaflet. Pharm Res 31(8):1989–1999. Epub 2014/02/20PubMedCrossRefGoogle Scholar
  93. 93.
    Lee J, Park SH, Seo IH, Lee KJ, Ryu W (2015) Rapid and repeatable fabrication of high A/R silk fibroin microneedles using thermally-drawn micromolds. Eur J Pharm Biopharm 94:11–19. Epub 2015/05/06PubMedCrossRefGoogle Scholar
  94. 94.
    Bariya SH, Gohel MC, Mehta TA, Sharma OP (2012) Microneedles: an emerging transdermal drug delivery system. J Pharm Pharmacol 64(1):11–29. Epub 2011/12/14PubMedCrossRefGoogle Scholar
  95. 95.
    Chandrasekaran SK, Darda S, Michaels AS, Cleary GW (1980) Therapeutic system for administering clonidine transdermally. US Patent 4,201,211Google Scholar
  96. 96.
    Enscore DJ, Gale RM (1985) Matrix composition for transdermal therapeutic system. US Patent 4,559,222Google Scholar
  97. 97.
    Sablotsky S, Questel JM, Leeson DJ (1989) Transdermal multipolymer drug delivery system. US Patent 4,814,168Google Scholar
  98. 98.
    Sablotsky S (1991) Transdermal acrylic multipolymer drug delivery system. US Patent 4,994,267Google Scholar
  99. 99.
    Nagai T, Takayama K, Okabe H (1992) Transdermal therapeutic formulation containing a limonene. US Patent 5,164,416Google Scholar
  100. 100.
    Sablotsky S, Gentile JA (1994) Method and device for the release of drugs to the skin. US Patent 5,300,291Google Scholar
  101. 101.
    Sablotsky S, Gentile JA (1997) Method and device for the release of drugs to the skin. US Patent 5,686,099Google Scholar
  102. 102.
    Cantor AS, Ocheltree TW, Robles CA (2012) Composition for transdermal delivery of Fentanyl. US Patent App. 13/275,498Google Scholar
  103. 103.
    Kirstgen E, Meconi R (2003) Estradiol-containing patch for transdermal application of hormones. US Patent 6,531,149Google Scholar
  104. 104.
    Venkatraman SS, Li S, Gale RM, Stepic J, Van Osdol WW (2003) Transdermal administration of fentanyl and analogs thereof. US Patent App. 10/098,656Google Scholar
  105. 105.
    Miller I (2013) Transdermal patch incorporating active agent migration barrier layer. US Patent 8,524,272Google Scholar
  106. 106.
    Langguth T, Bracht S, Dittgen M, Huber P, Schenk D (2014) Transdermal delivery of hormones without the need of penetration enhancers. US Patent 8,668,925Google Scholar
  107. 107.
    Cormier MJ, Padmanabhan RV (2006) Transdermal electrotransport drug delivery systems with reduced abuse potential. US Patent App. 11/361,198Google Scholar
  108. 108.
    Pearlman R, Oeswein JQ (1992) Human growth hormone formulation. US Patent 5,096,885Google Scholar
  109. 109.
    Hanatani A, Sekiya J, Terashi S, Nishi S, Washiro S, Akemi H (2008) Stabilized donepezil-containing patch preparation. US Patent App. 11/987,480Google Scholar
  110. 110.
    Hwang SS, Gale RM (2017) Once-a-day replacement transdermal administration of Fentanyl. US Patent App. 15/389,599Google Scholar
  111. 111.
    Alam A, Reichel E, Busbee B (2009) Method of inducing topical anesthesia and transdermal patch. US Patent App. 12/354,422Google Scholar
  112. 112.
    Ma X, Audett J, Soni PL, Singh N, Bailey SE (1998) Transdermal drug delivery sytem for the administration of tamsulosin, and related compositions and methods of use. US Patent 5,843,472Google Scholar
  113. 113.
    Trautman JC, Kim HL (2005) Device for enhancing transdermal agent flux. US Patent 6,953,589Google Scholar
  114. 114.
    Khavari P, Fan H (2000) Introduction of nucleic acid into skin cells by topical application. US Patent 6,087,341Google Scholar
  115. 115.
    Yeoh T (2012) Current landscape and trends in transdermal drug delivery systems. Ther Deliv 3(3):295–297PubMedCrossRefGoogle Scholar
  116. 116.
    Yeoh T (2011) Profiles of recently approved transdermal drug delivery systems. Part II: matrix-type fentanyl transdermal systems – design variation and 3(5):9–15Google Scholar
  117. 117.
    Yeoh T (2011) Profiles of recently approved transdermal drug delivery systems. Part 1: exelon patch – example of life cycle strategy for successful products; generic clonidine transdermal systems – design and delivery attributes 3(4):10–17Google Scholar
  118. 118.
    FDA. Center for Drug Evaluation and Research (CDER), US Department of Health and Human Services Guidance for industry (2011) Residual Drug in Transdermal and Related Drug Delivery SystemsGoogle Scholar
  119. 119.
    Lambert PH, Laurent PE (2008) Intradermal vaccine delivery: will new delivery systems transform vaccine administration? Vaccine 26(26):3197–3208. Epub 2008/05/20PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Avinash Kumar Seth
    • 1
  1. 1.Department of PharmacySumandeep Vidyapeeth, Deemed to be UniversityVadodaraIndia

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