Transdermal patches: Design and current approaches to painless drug delivery

Open access

Abstract

Use of transdermal patches can evade many issues associated with oral drug delivery, such as first-pass hepatic metabolism, enzymatic digestion attack, drug hydrolysis and degradation in acidic media, drug fluctuations, and gastrointestinal irritation. This article reviews various transdermal patches available in the market, types, structural components, polymer role, and the required assessment tools. Although transdermal patches have medical applications for smoking cessation, pain relief, osteoporosis, contraception, motion sickness, angina pectoris, and cardiac disorders, advances in formulation development are ongoing to make transdermal patches capable of delivering more challenging drugs. Transdermal patches can be tailored and developed according to the physicochemical properties of active and inactive components, and applicability for long-term use. Therefore, a number of chemical approaches and physical techniques for transdermal patch development are under investigation.

1. L. Zhang and S. Mao, Application of quality by design in the current drug development, As. J. Pharm. Sci. 12 (2017) 1–8; https://doi.org/10.1016/j.ajps.2016.07.006

2. M. R. Prausnitz and R. Langer, Transdermal drug delivery, Nat. Biotechnol. 26 (2008) 1261–1268; https://doi.org/10.1038/nbt.1504

3. M. J. Tsai, I. J. Lu, Y. S. Fu, Y.P. Fang, Y. B. Huang and P. C. Wu, Nanocarriers enhance the transdermal bioavailability of resveratrol: In-vitro and in-vivo study, Colloids Surf. B Biointerfaces 148 (2016) 650–656; https://doi.org/10.1016/j.colsurfb.2016.09.045

4. A. Simon and M. I. Amaro, A. M. Healy, L. M. Cabral and V. P. de Sousa, Comparative evaluation of rivastigmine permeation from a transdermal system in the Franz cell using synthetic membranes and pig ear skin with in vivo-in vitro correlation, Int. J. Pharm. 512 (2016) 234–241; https://doi.org/10.1016/j.ijpharm.2016.08.052

5. E. M. Pridgen, F. Alexis and O. C. Farokhzad, Polymeric nanoparticle drug delivery technologies for oral delivery applications, Expert Opin. Drug. Deliv. 12 (2015) 1459–1473; https://doi.org/10.1517/17425247.2015.1018175

6. M. Arafat, Approaches to achieve an oral controlled release drug delivery system using polymers: a recent review, Int. J. Pharm. Pharm. Sci. 7 (2015) 16–21.

7. R. Gannu, Y. V. Vishnu, V. Kishan and Y. M. Rao, Development of nitrendipine transdermal patches: in vitro and ex vivo characterization, Curr. Drug Deliv. 4 (2007) 69–76.

8. M. Arafat, Bilosomes as a Drug Delivery System, in Thesis, Doctor of Philosophy, University of Otago, NZ, (2012); http://hdl.handle.net/10523/2157

9. M. N. Pastore, Y. N. Kalia, M. Horstmann and M. S Roberts, Transdermal patches: history, development and pharmacology, Br. J. Pharmacol. 172 (2015) 2179–2209; https://doi.org/10.1111/bph.13059

10. M. B. Brown, G. P. Martin, S. A. Jones and F. K. Akomeah, Dermal and transdermal drug delivery systems: Current and future prospects, Drug Del. 13 (2008) 175–187; https://doi.org/10.1080/10717540500455975

11. K. S. Paudel, M. Milewski, C. L. Swadley, N. K Brogden, P. Ghosh and A. L. Stinchcomb, Challenges and opportunities in dermal/transdermal delivery, Ther. Deliv. 1 (2010) 109–131.

12. G. A. Van Norman, Drugs, Devices, and the FDA: Part 2: An overview of approval processes: FDA approval of medical devices, JACC: Bas. Transl. Sci. 1 (2016) 277–287; https://doi.org/10.1016/j.jacbts.2016.03.009

13. M. Isaac and C. Holvey, Transdermal patches: the emerging mode of drug delivery system in psychiatry, Ther. Adv. Psychopharmacol. 2 (2012) 255–263; https://doi.org/10.1177/2045125312458311

14. A. Z. Alkilani, M. T. C. McCrudden and R. F. Donnelly, Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum, Pharmaceutics 7 (2015) 438–470; https://doi.org/10.3390/pharmaceutics7040438

15. M. Murphy and A. J. Carmichael, Transdermal drug delivery systems and skin sensitivity reactions. Incidence and management, Am. J. Clin. Dermatol. 1 (2000) 361–368.

16. P. Karandea and S. Mitragotrib, Enhancement of transdermal drug delivery via synergistic action of chemicals, Biochim. Biophys. Acta 1788 (2009) 2362–2373; https://doi.org/10.1016/j.bbamem.2009.08.015

17. J. Suksaeree, C. Monton, F. Madaka, T. Chusut, W. Saingam, W. Pichayakorn and P. Boonme, Formulation, physicochemical characterization, and in vitro study of chitosan/HPMC blends-based herbal blended patches, AAPS Pharm. Sci. Tech. 16 (2015) 171–181; https://doi.org/10.1208/s12249-014-0216-6

18. N. S. Chandrashekar and R. H. S. Rani, Physicochemical and pharmacokinetic parameters in drug selection and loading for transdermal drug delivery, Indian J. Pharm. Sci. 70 (2008) 94–96; https://doi.org/10.4103/0250-474X.40340

19. M. Arafat, The effect of intestinal bile on the stability of lipid-based vesicular system used as oral drug carriers, Glob. Drug Therap. 2 (2016) 1–2; https://doi.org/10.15761/GDT.1000109

20. J. Suksaereeab, L. Charoenchaib, F. Madakab, C. Montonb, A. Sakunpak, T. Charoonratana and W. Zingiber, Cassumunar blended patches for skin application: Formulation, physicochemical properties, and in vitro studies, Asian J. Pharm. Sci. 10 (2015) 341–349; https://doi.org/10.1016/j.ajps.2015.03.001

21. A. C. Willams and B. W. Barry, Penetration enhancers, Adv. Drug. Del. Rev. 56 (2004) 603–618.

22. S. D. Saoji, S. C. Atram, P. W. Dhore, P. S. Deole, N. A. Raut and V. S. Dave, Influence of the component excipients on the quality and functionality of a transdermal film formulation, AAPS Pharm. Sci. Tech. 16 (2015) 1344–1356; https://doi:10.1208/s12249-015-0322-0

23. M. Imani, F. Lahooti-Fard, S. M. Taghizadeh and M Takrousta, Effect of adhesive layer thickness and drug loading on estradiol crystallization in a transdermal drug delivery system, AAPS Pharm. Sci. Tech. 11 (2010) 1268–1275; https://doi.org/10.1208/s12249-010-9494-9

24. S. Dhiman, T. G. Singh and A. K. Rehni, Transdermal patches: A recent approach to new drug delivery system, Int. J. Pharm. Pharm. Sci. 3 (2011) 26–34.

25. S. Rani, K. Saroha, N. Syan and P. Mathur, Transdermal patches a successful tool in transdermal drug delivery system: An overview, Der Pharm. Sinica 2 (2011) 17–29.

26. B. Berner and V. A. John, Pharmacokinetic characterization of transdermal delivery system, J. Clin. Pharmacol. 26 (1994) 121–134.

27. S. Mutalik and N. Udupa, Pharmacological evaluation of membrane-moderated transdermal system of glipizide, Clin. Exp. Pharmacol. Physiol. 33 (2006) 17-26.

28. C. L. Stevenson, J. T. Jr. Santini and R. Langer, Reservoir-based drug delivery systems utilizing microtechnology, Adv. Drug Deliv. Rev. 64 (2012) 1590–1602; https://doi.org/10.1016/j.addr.2012.02.005

29. P. J. Hughes, M. K. Freeman and T. M. Wensel, Appropriate use of transdermal drug delivery systems, J. Nurs. Edu. Pract. 3 (2013) 129–138.

30. S. Cherukuri, U. R. Batchu, K. Mandava, V. Cherukuri, K. R. Ganapuram, Formulation and evaluation of transdermal drug delivery of topiramate, Int. J. Pharm. Investig. 7 (2017) 10–17; https://doi.org/10.4103/jphi.JPHI_35_16

31. E. Abd, S. A. Yousef, M. N. Pastore, K. Telaprolu, Y. H. Mohammed, S. Namjoshi, J. E. Grice and M. S. Roberts, Skin models for the testing of transdermal drugs, Clin. Pharmacol. 8 (2016) 163–176; https://doi.org/10.2147/CPAA.S64788

32. A. Z. Alkilani, M. T. C. McCrudden and R. F. Donnelly, Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum, Pharmaceutics 7 (2015) 438–470; https://doi.org/10.3390/pharmaceutics7040438

33. H. Trommer and R. H. H. Neubert, Overcoming the stratum corneum: the modulation of skin penetration, Skin Pharmacol. Physiol. 19 (2006) 106–121; https://doi.org/10.1159/000091978

34. S. S. Davis and L. Illum, Drug Delivery Systems for Challenging Molecules, Int. J. Pharm. 176 (1998) 1–8.

35. A. Ahmed, N. Karki, R. Charde, M. Charde and B. Gandhare, Transdermal drug delivery systems: An overview, Int. J. Biomed. Adv. Res. 2 (2010) 38–56.

36. S. R. W. Baker and J. Heller, Material Selection for Transdermal Delivery Systems, in Transdermal Drug Delivery: Developmental Issues and Research Initiatives (Eds. J. Hadgraft and R. H. Guys), Marcel Dekker, Inc., New York 1989, pp. 293–311.

37. M. Guyot and F. Fawaz, Design and in vitro evaluation of adhesive matrix for transdermal delivery of propranolol, Int. J. Pharm. 204 (2000) 171–182.

38. Ł. Zimmer, R. Kasperek and E. Poleszak, Modern polymers in matrix tablets technology, Polim. Med. 44 (2014)189–196.

39. M. Guyot and F. Fawaz, Design and in vitro evaluation of adhesive matrix for transdermal delivery of propranolol, Int. J. Pharm. 204 (2000) 171–182.

40. A. F. El-Kattan, C. S. Asbill and B. B. Michniak, The effect of terpene enhancer lipophilicity on the percutaneous permeation of hydrocortisone formulated in HPMC gel systems, Int. J. Pharm. 198 (2000) 179–189.

41. R. Sutinen, P. Paronen, V. Saano and A. Urtti, Water-activated, pH-controlled patch in transdermal administration of timolol: II. Drug absorption and skin irritation, Eur. J. Pharm. Sci. 11 (2000) 25–31.

42. H. Iwase, J. I. Sudo, J. Terui, K. Kakuno, T. Watanabe, K. Takayama and T. Nagai, Transdermal absorption of L-dopa from a new system composed of two separate layers of L-dopa and hydrogel in rats, Drug Dev. Ind. Pharm. 26 (2000) 755–759.

43. M. K. Kim, H. Zhao, C. H. Lee and D. D. Kim, Formulation of a reservoir-type testosterone trans-dermal delivery system, Int. J. Pharm. 219 (2001) 51–59.

44. H. Gabiga, K. Cal and S. Janicki, Effect of penetration enhancers on isosorbide dinitrate penetration through rat skin from a transdermal therapeutic system, Int. J. Pharm. 199 (2000) 1–6.

45. S. Ohmori, T. Hayash, M. Kawase, S. Saito, K. Sugibayashi and Y. Morimoto, Transdermal delivery of the potent analgesic dihydroetorphine: kinetic analysis of skin permeation and analgesic effect in the hairless rat, J. Pharm. Pharmacol. 52 (2000) 1437–1449.

46. T. Pongjanyakul, S. Prakongpan and A. Priprem, Permeation studies comparing cobra skin with human skin using nicotine transdermal patches, Drug Dev. Ind. Pharm. 26 (2000) 635–642.

47. S. M. Al-Saidan,Y. S. R. Krishnaiah, D. V. Chandrasekhar, J. K. Lalla, B. Rama, B. Jayaram and P. Bhaskar, Formulation of an HPMC gel drug reservoir system with ethanol-water as a solvent system and limonene as a penetration enhancer for enhancing in vitro transdermal delivery of nicorandil, Skin Pharmacol. Physiol. 17 (2004) 310–320.

48. Y. S. Krishnaiah, P. Bhaskar and V. Satyanarayana, Penetration-enhancing effect of ethanol-water solvent system and ethanolic solution of carvone on transdermal permeability of nimodipine from HPMC gel across rat abdominal skin, Pharm. Dev. Technol. 9 (2004) 63–74.

49. Y. Tanwar, C. Chauhan and A. Sharma, Development and evaluation of carvedilol transdermal patches, Acta Pharm. 57 (2007) 151–159.

50. A. Wahid, B. Sridhar and S. Shivakumar, Preparation and evaluation of transdermal drug delivery system of etoricoxib using modified chitosan, Indian J. Pharm. Sci. 70 (2008) 455–460.

51. B. Winblad and J. C. Machado. Use of rivastigmine transdermal patch in the treatment of Alzheimer’s disease, Expert Opin. Drug Deliv. 5 (2008) 1377–1386.

52. C. Ren, L. Fang, L. Ling, Q. Wang, S. Liu, L. Zhao and Z. He, Design and in vivo evaluation of an indapamide transdermal patch, Int. J. Pharm. 370 (2009) 129–135.

53. S. Jayaprakash, S. M. Halith, P. M. Firthouse and N. M. Yasmin, Preparation and evaluation of celecoxib transdermal patches, Pak. J. Pharm. Sci. 23 (2010) 279–283.

54. Y. C. Ah, J. K. Choi, Y. K. Choi, H. M. Ki and J. H. Bae, A novel transdermal patch incorporating meloxicam: in vitro and in vivo characterization, Int. J. Pharm. 385 (2010) 12–19.

55. P. Anitha, S. Ramkanth, M. T. Saleem, K. Umasankari, B. P. Reddy and M. Chetty, Preparation, in-vitro and in-vivo characterization of transdermal patch containing glibenclamide and atenolol: a combinational approach, Pak. J. Pharm. Sci. 24 (2011) 155–163.

56. D. M. Panchaxari, S. Pampana, T. Pal, B. Devabhaktuni and A. K. Aravapalli, Design and characterization of diclofenac diethylamine transdermal patch using silicone and acrylic adhesives combination, Daru 21 (2013) 6; https://doi.org/10.1186/2008-2231-21-6

57. H. M. Wolff, Optimal process design for the manufacture of transdermal drug delivery systems, Pharm. Sci. Technol. Today. 3 (2000) 173–181.

58. L. Bromberg, Crosslinked poly(ethylene glycol) networks as reservoirs for protein delivery, J. Appl. Polym. Sci. 59 (1996) 459–466.

59. P. Costa, D. C. Ferreira, R. Morgado and J. S. Lobo, Design and evaluation of a lorazepam transdermal delivery system, Drug Dev. Ind. Pharm. 23 (1997) 939–944.

60. P. Minghetti, F. Cilurzo and L. Montanari, Evaluation of adhesive properties of patches based on acrylic matrices, Drug Dev. Ind. Pharm. 25 (1999) 1–6.

61. P. R. Rao and P. V. Diwan, Formulation and in vitro evaluation of polymeric films of diltiazem hydrochloride and indomethacin for transdermal administration, Drug Dev. Ind. Pharm. 24 (1998) 327–336.

62. S. S. Baek and S. H. Hwang, Eco-friendly UV-curable pressure sensitive adhesives containing acryloyl derivatives of monosaccharides and their adhesive performances, Int. J. Adhes. Adhes. 70 (2016) 110–116; https://doi.org/10.1016/j.ijadhadh.2016.06.002

63. S. Banerjee, P. Chattopadhyay, A. Ghosh, P. Datta and V. Veer, Aspect of adhesives in transdermal drug delivery systems, Int. J. Adhes. Adhes. 50 (2014) 70–84; https://doi.org/10.1016/j.ijadhadh.2014.01.001

64. C. Fang, Y. Jing, Y. Zong and Z. Lin, Effect of N,N-dimethylacrylamide (DMA) on the comprehensive properties of acrylic latex pressure sensitive adhesives, Int. J. Adhes. Adhes. 71 (2016) 105–111; https://doi.org/10.1016/j.ijadhadh.2016.09.003

65. V. G. Kadajji and G. V. Betageri. Water soluble polymers for pharmaceutical applications, Polymers 3 (2011) 1972–2009; https://doi.org/10.3390/polym3041972

66. I. Benedek, M. M. Feldstein, N. Willenbacher and O. V. Lebedeva, Polyisobutene-Based Pressure-Sensitive Adhesives. Technology of Pressure-Sensitive Adhesives and Products, CRC Press; 2008. p. 4-1-4-18.

67. X. Tong, Q. Wang, H. X. Wang, X. H. Li, W. Wu and X. Y. Chey, Fabrication of pH sensitive amphiphilic hot-melt pressure sensitive adhesives for transdermal drug delivery system, Int. J. Adhes. Adhes. 48 (2014) 217–223; https://doi.org/10.1016/j.ijadhadh.2013.09.025

68. D. J. Lyman and B. H. Loo, New synthetic membranes for dialysis. IV. A copolyether–urethane membrane system, J. Biomed. Mater. Res. 1 (1967) 17–26.

69. V. Stannett, W. Koros, D. Paul, H. Lonsdale and R. Baker, Recent Advances in Membrane Science and Technology, in Advances in Polymer Sciences, Vol. 32, Chemistry, Springer Verlag, Berlin 1979, pp. 69–121.

70. D. G. Maillard-Salin, P. Becourt and G. Couarraze, Physical evaluation of a new patch made of a progestomimetic in a silicone matrix, Int. J. Pharm. 199 (2000) 29–38.

71. D. G. Maillard-Salin, P. Becourt and G. Couarraze, A study of the adhesive-skin interface: correlation between adhesion and passage of a drug, Int. J. Pharm. 200 (2000) 121–126.

72. C. D. Ebert, W. Heiber, R. Andriola and P. Williams, Development of a novel transdermal system design, J. Control. Release. 6 (1987) 107–111.

73. A. Flo, T. Cambras, A. Díez-Noguera and A. Calpena, Melatonin pharmacokinetics after transdermal administration changes according to the time of the day, Eur. J. Pharm. Sci. 96 (2017) 164–170; https://doi.org/10.1016/j.ejps.2016.09.020

74. I. Som, K. Bhatia and M. Yasir, Status of surfactants as penetration enhancers in transdermal drug delivery, J. Pharm. Bioallied Sci. 4 (2012) 2–9; https://doi.org/10.4103/0975-7406.92724

75. Y. Chen, P. Quan, X. Liu, M. Wang and L. Fang, Novel chemical permeation enhancers for transdermal drug delivery, Asian J. Pharm. Sci. 9 (2014) 51–64.

76. Q. D. Pham, S. Björklund, J. Engblom, D. Topgaard and E. Sparr, Chemical penetration enhancers in stratum corneum – Relation between molecular effects and barrier function, J. Control. Release 232 (2016) 175–187; https://doi.org/10.1016/j.jconrel.2016.04.030

77. G. El Maghraby, A. C. Williams and B. Barry, Interactions of surfactants (edge activators) and skin penetration enhancers with liposomes, Int. J. Pharm. 276 (2004) 143–161.

78. M. Arafat, C. Kirchhoefer, M. Mikov, M. Sarfraz and R. Löbenberg, Nanosized liposomes containing bile salt: A vesicular nanocarrier for enhancing oral bioavailability of BCS class III drug, J. Pharm. Pharm. Sci. 20 (2017) 305–318; https://doi.org/10.18433/J3CK88

79. M. Arafat, C. Kirchhoefer and M. Mikov, Mixed micelles loaded with bile salt: an approach to enhance intestinal transport of the BCS class III drug cefotaxime in rats, Eur. J. Drug Metab. Pharmacokinet. 42 (2017) 635–645; https://doi.org/10.1007/s13318-016-0375-9

80. T. E. G. K. Murthy and V. S. Kishore, Effect of casting solvent and polymer on permeability of propranolol hydrochloride through membrane controlled transdermal drug delivery system, Indian J. Pharm. Sci. 69 (2007) 646–650; https://doi.org/10.4103/0250-474X.38469

81. A. Alexander, S. Dwivedi, T. K. Giri, S. Saraf and D. K. Tripathi, Approaches for breaking the barriers of drug permeation through transdermal drug delivery, J. Control. Release 164 (2012) 26–40; https://doi.org/10.1016/j.jconrel.2012.09.017

82. Guideline on quality of transdermal patches. European Medicines Agency, Committee for Medicinal Products for Human Use (2014) 1-27. EMA/CHMP/QWP/608924/2014

83. H. Lim and S. W. Hoag, Plasticizer effects on physical–mechanical properties of solvent cast Soluplus® films, AAPS Pharm. Sci. Tech. 14 (2013) 903–910; https://doi.org/10.1208/s12249-013-9971-z

84. M. Arafat, Z. Ahmed and O. Arafat, Comparison between generic drugs and brand name drugs from bioequivalence and thermoequivalence prospective, Int. J. Pharm. Pharm. Sci. 9 (2017) 1–4.

85. M. Bharkatiya, R. Nema and M. Bhatnagar, Designing and characterization of drug free patches for transdermal application, Int. J. Pharm. Sci. Drug Res. 2 (2012) 35–39.

86. K. C. Garala, A. J. Shinde and P. H. Shah, Formulation and in-vitro characterization of monolithic matrix transdermal systems using HPMC/Eudragit S 100 polymer blends, Int. J. Pham. Pharm. Sci. 1 (2009) 108–120.

87. J. M. Prosser, B. E. Jones and L. Nelson, Complications of oral exposure to fentanyl transdermal delivery system patches, J. Med. Toxicol. 6 (2010) 443–447.

88. J. Singh, K. Tripathi and T. Sakya, Effect of penetration enhancers on the in vitro transport of ephedrine through rat skin and human epidermis from matrix based transdermal formulations, Drug Dev. Ind. Pharm. 19 (1993) 1623–1628.

89. N. Maftoona, H. S. Ramaswamy and M. Marcotte, Evaluation of factors affecting barrier, mechanical and optical properties of pectin-based films using response surface methodology, J. Food. Process Eng. 30 (2007) 539–563; https://doi.org/10.1111/j.1745-4530.2007.00123.x

90. A. Singh and A. Bali, Formulation and characterization of transdermal patches for controlled delivery of duloxetine hydrochloride, J. Anal. Sci. Technol. 7 (2016) 25; https://doi.org/10.1186/s40543-016-0105-6

91. J. Wiechers, Use of chemical penetration enhancers in transdermal drug delivery – possibilities and difficulties, Acta Pharm Nord. 4 (1992) 123.

92. S. Banerjee, P. Chattopadhyay, A. Ghosh, P. Datta and V. Veer, Aspect of adhesives in transdermal drug delivery systems, Int. J. Adhes. Adhes. 50 (2014) 70–84.

93. A. M. Wokovich, S. Prodduturi, W. H. Doub, A. S. Hussain and L. F. Buhse, Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy and quality attribute, Eur. J. Pharm. Biopharm. 64 (2006) 1–8.

94. A. J. Steven-Fountain, A. G. Atkins, G. Jeronimidis, J. F. V. Vincent, D. F. Farrar and R. A. Chivers, The effect of flexible substrates on pressure-sensitive adhesive performance, Int. J. Adhes. Adhes. 22 (2002) 423–430.

95. G. Thakur, A. Singh and I. Singh, Formulation and evaluation of transdermal composite films of chitosan-montmorillonite for the delivery of curcumin, Int. J. Pharm. Investig. 6 (2016) 23–31; https://doi.org/10.4103/2230-973X.176468

96. T. Kamal, M. Sarfraz, M. Arafat, M. Mikov and N Rahman, Cross-linked guar gum and sodium borate based microspheres as colon-targeted anticancer drug delivery systems for 5-fluorouracil, Pak. J. Pharm. Sci. 30 (2017) 2329–2336.

97. O. A. Hanbali, R. Hamed, M. Arafat, Y. Bakkour, H. Matubsi, R. Mansour, Y. Bataineh, M. Aldhoun, M. Sarfraz and A. K. Yousef Dardas, Formulation and evaluation of diclofenac controlled release matrix tablets made of HPMC and Poloxamer 188 polymer: An assessment on mechanism of drug release, Pak. J. Pharm. Sci. 31 (2018) 345–351.

98. T. Z. Marques, R. Santos-Oliveira, L. B. de Siqueira, V. S. Cardoso, Z. M. de Freitas, R. C. Barros, A. L. Villa, M. S. Monteiro, E. P. Santos and E. Ricci-Junior, Development and characterization of a nanoemulsion containing propranolol for topical delivery, Int. J. Nanomedicine 13 (2018) 2827–2837; https://doi.org/10.2147/IJN.S164404

99. C. S. Cerqueira-Coutinho, V. E. De Campo, A. L. Rossi, V. F. Veiga, C. Holandino, Z. M. Freitas, E. Ricci-Junior, C. R. Mansur, E. P. Santos and R. Santos-Oliveira, Comparing in vivo biodistribution with radiolabeling and Franz cell permeation assay to validate the efficacy of both methodologies in the evaluation of nanoemulsions: a safety approach, Nanotechnology 27 (2016) 015101; https://doi.org/10.1088/0957-4484/27/1/015101

100. J. Wang, Y. Wei, Y. R. Fei, L. Fang, H. S. Zheng, C. F. Mu, F. Z. Li and Y. S. Zhang, Preparation of mixed monoterpenes edge activated PEGylated transfersomes to improve the in vivo transdermal delivery efficiency of sinomenine hydrochloride, Int. J. Pharm. 533 (2017) 266–274; https://doi.org/10.1016/j.ijpharm.2017.09.059

101. I. I. Abu Hashim, N. F. Abo El-Magd, A. R. El-Sheakh and M. F. Hamed, Pivotal role of Acitretin nanovesicular gel for effective treatment of psoriasis: ex vivo–in vivo evaluation study, Int. J. Nanomedicine 13 (2018) 1059–1079; https://doi.org/10.2147/IJN.S156412

102. A. Manosroi, C. Chankhampan, W. Manosroi and J. Manosroi, Transdermal absorption enhancement of papain loaded in elastic niosomes incorporated in gel for scar treatment, Eur. J. Pharm. Sci. 48 (2013) 474–483; https://doi.org/10.1016/j.ejps.2012.12.010

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