Azone analogues: Classification, design, and transdermal penetration principles

Medicinal Research Reviews

Volumn 32, Issue 5, 2012, Pages 907-947

  Jampilek, Josef ^a,b   Brychtova, Katerina ^a  

^a UNIVERSITY OF VETERINARY AND PHARMACEUTICAL SCIENCES   (Czech Republic)

^b Zentiva Prague   (Czech Republic)

Author keywords

Azone like enhancers; Classification of enhancers; SAR QSAR; Transdermal penetration enhancers; Transdermal penetration principles

Indexed keywords

ALCOHOL DERIVATIVE; ALKANOIC ACID; AMINO ACID DERIVATIVE; ARACHIDONIC ACID; DECYL METHYL SULFOXIDE; DIMETHYL SULFOXIDE; FATTY ACID DERIVATIVE; FATTY ACID ESTER; GLYCINE DERIVATIVE; HEXYL OLEATE; LACTAM DERIVATIVE; LAURIC ACID; LAURIC ACID DERIVATIVE; LAUROCAPRAM; LINOLEIC ACID; LINOLENIC ACID; MACROGOL; MYRISTIC ACID; MYRISTIC ACID ISOPROPYL ESTER; N ACETYLPROLINE; N,N DIMETHYLACETAMIDE; N,N DIMETHYLFORMAMIDE; OLEIC ACID; POLYOL; SERINE DERIVATIVE; SULFOXIDE; UNCLASSIFIED DRUG; UNDECANOIC ACID; UNINDEXED DRUG; UREA; UREA DERIVATIVE;

ARTICLE; CHEMICAL STRUCTURE; DRUG DELIVERY SYSTEM; DRUG DESIGN; DRUG DOSAGE FORM; DRUG PENETRATION; HUMAN; NONHUMAN; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, CUTANEOUS; AZEPINES; DRUG DESIGN; HUMANS; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; SKIN; SKIN ABSORPTION;

EID: 84864851442     PISSN: 01986325     EISSN: 10981128     Source Type: Journal    
DOI: 10.1002/med.20227     Document Type: Article

References (238)

1. Barr M. Percutaneous absorption. J Pharm Sci 1962;51:395-409.
2. Idson B. Percutaneous absorption. J Pharm Sci 1975;64:901-924.
3. 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;102:4688-4693.
4. Swart PJ, Toulouse FAM, De Zeeuw RA. The influence of Azone on the transdermal penetration of the dopamine D2 agonist N-0923 in freely moving rats. Int J Pharm 1992;88:165-170.
5. Muller W, Peck JV. Transdermal therapeutic system for treating parkinsonism. U.S. Patent 7, 413, 747; 2008.
6. Moller HJ, Hampel H, Hegerl U, Schmitt W, Walter K. Double-blind, randomized, placebo-controlled clinical trial on the efficacy and tolerability of a physostigmine patch in patients with senile dementia of the Alzheimer type. Pharmacopsychiatry 1999;32:99-106.
7. Lee KC, Chen JJ. Transdermal selegiline for the treatment of major depressive disorder. Neuropsychiatr Dis Treat 2007;3:527-537.
8. Wong TW. Chitosan and its use in design of insulin delivery system. Recent Pat Drug Deliv Formul 2009;3:8-25.
9. Chandrashekar NS, Hiremath SRR. Transdermal delivery of 5-fluorouracil for induced Ehrlich ascites carcinoma tumor in Balb/c mice and pharmacokinetic study. Recent Patents Anti-Canc Drug Discov 2007;2:235-239.
10. Chandrashekar NS, Prasanth VV. Clinical evaluation of 5-fluorouracil from transdermal patches on EAC and DLA cell-induced tumors in mice. Asian Pac J Cancer Prev 2008;9:437-440.
11. Finnin BC, Morgan TM. Transdermal penetration enhancers: Applications, limitations, and potential. J Pharm Sci 1999;88:955-958.
12. Vasilev AE, Krasnyuk II, Ravikumar S, Tokhmakhchi VN. Transdermal therapeutic systems for controlled drug release. Pharm Chem J 2001;35:613-626.
13. Steinert PM. The complexity and redundancy of epithelial barrier function. J Cell Biol 2000;151:F5-F7.
14. Agache P, Humbert P. Measuring the skin. Berlin, Heidelberg: Springer; 2004.
15. Holbrook KA, Odland GF. Regional differences in the thickness (cell layers) of the human stratum corneum: An ultrastructural analysis. J Invest Dermatol 1974;62:415-422.
16. Elias PM. Structure and function of the stratum corneum permeability barrier. Drug Dev Res 1988;13:97-105.
17. Moghimi HR, Williams AC, Barry BW. A lamellar matrix model for the stratum corneum intercellular lipids. I. Characterization and comparison with stratum corneum intercellular structure. Int J Pharm 1996;131:103-115.
18. Suhonen TM, Bouwstra JA, Urtti A. Chemical enhancement of percutaneous absorption in relation to stratum corneum structural alterations. J Control Release 1999;59:149-161.
19. Scheuplein RJ, Morgan LJ. Bound water in keratin membranes measured by a microbalance technique. Nature 1967;214:456-458.
20. Nemes Z, Steinert PM. Bricks and mortar of the epidermal barrier. Exp Mol Med 1999;31:5-19.
21. Benson HAE. Transdermal drug delivery: Penetration enhancement techniques. Curr Drug Deliv 2005;2:23-33.
22. Potts RO, Francoeur ML. The influence of stratum corneum morphology on water permeability. J Invest Dermatol 1991;96:495-499.
23. Garson JC, Doucet J, Leveque JL, Tsoucaris G. Oriented structure in human stratum corneum revealed by X-ray diffraction. J Invest Dermatol 1991;96:43-49.
24. Bouwstra JA, Gooris GS, Salomons-de Vries MA, van der Spek JA, Bras W. Structure of human stratum corneum as a function of temperature and hydration: A wide-angle X-ray diffraction study. Int J Pharm 1992;84:205-216.
25. Williams ML, Elias PM. The extracellular matrix of stratum corneum: Role of lipids in normal and pathological function. Crit Rev Ther Drug Carr Syst 1987;3:95-122.
26. Norlen L. Skin barrier structure and function: The single gel phase model. J Invest Dermatol 2001;117:830-836.
27. Freinkel RK, Woodley DT. The biology of the skin. New York: Parthenon Publishing; 2001.
28. Vavrova K, Zbytovska J, Hrabalek A. Amphiphilic transdermal permeation enhancers: Structure-activity relationships. Curr Med Chem 2005;12:2273-2291.
29. Prausnitz MR, Mitragotri S, Langer R. Current status and future potential of transdermal drug delivery. Nat Rev Drug Discov 2004;3:115-124.
30. Illel B. Formulation for transfollicular drug administration: Some recent advances. Crit Rev Ther Drug Carr Syst 1997;14:207-219.
31. Barry BW. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci 2001;14:101-114.
32. Scheuplein RJ, Blank IH. Permeability of the skin. Physiol Rev 1971;51:702-747.
33. Ledger PW. Skin biological issues in electrically enhanced transdermal delivery. Adv Drug Deliv Rev 1992;9:289-307.
34. Pikal MJ. The role of electroosmotic flow in transdermal iontophoresis. Adv Drug Deliv Rev 2001;46:281-305.
35. Riviere JE, Heit MC. Electrically-assisted transdermal drug delivery. Pharm Res 1997;14:687-697.
36. Prausnitz MR. A practical assessment of transdermal drug delivery by skin electroporation. Adv Drug Deliv Rev 1999;35:61-76.
37. Prausnitz MR, Edelman ER, Gimm JA, Langer R, Weaver JC. Transdermal delivery of heparin by skin electroporation. Nat Biotechnol 1995;13:1205-1209.
38. Sen A, Daly ME, Hui SW. Transdermal insulin delivery using lipid enhanced electroporation. Biochim Biophys Acta Biomembr 2002;1564:5-8.
39. Misra A, Ganga S, Upadhyay P. Needle-free, non-adjuvanted skin immunization by electroporation-enhanced transdermal delivery of diphtheria toxoid and a candidate peptide vaccine against hepatitis B virus. Vaccine 1999;18:517-523.
40. Ueda H, Mutoh M, Seki T, Kobayashi D, Morimoto Y. Acoustic cavitation as an enhancing mechanism of low-frequency sonophoresis for transdermal drug delivery. Biol Pharm Bull 2009;32:916-920.
41. Ogura M, Paliwal S, Mitragotri S. Low-frequency sonophoresis: Current status and future prospects. Adv Drug Deliv Rev 2008;60:1218-1223.
42. Smith NB, Lee S, Shung KK. Ultrasound-mediated transdermal in vivo transport of insulin with low-profile cymbal arrays. Ultrasound Med Biol 2003;29:1205-1210.
43. Mitragotri S, Blankschtein D, Langer R. Ultrasound-mediated transdermal protein delivery. Science 1995;269:850-853.
44. Henry S, McAllister DV, Allen MG, Prausnitz MR. Microfabricated microneedles: A novel approach to transdermal drug delivery. J Pharm Sci 1998;87:922-925.
45. McAllister DV, Wang PM, Davis SP, Park JH, Canatella PJ, Allen MG, Prausnitz MR. Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies. Proc Natl Acad Sci USA 2003;100:13755-13760.
46. Mitragotri S. Synergistic effect of enhancers for transdermal drug delivery. Pharm Res 2000;17:1354-1359.
47. Naik A, Kalia YN, Guy RH. Transdermal drug delivery: Overcoming the skin's barrier function. Pharm Sci Technol Today 2000;3:318-326.
48. Karande P, Jain A, Mitragotri S. Relationships between skin's electrical impedance and permeability in the presence of chemical enhancers. J Control Release 2006;110:307-313.
49. Ganga S, Ramarao J, Singh J. Effect of Azone on the iontophoretic transdermal delivery of metoprolol tartrate through human epidermis in vitro. J Control Release 1996;42:57-64.
50. Johnson ME, Mitragotri S, Patel A, Blankschtein D, Langer R. Synergistic effects of chemical enhancers and therapeutic ultrasound on transdermal drug delivery. J Pharm Sci 1996;85:670-679.
51. Mitragotri S, Ray D, Farrell J, Tang H, Yu B, Kost J, Blankschtein D, Langer R. Synergistic effect of low-frequency ultrasound and sodium lauryl sulfate on transdermal transport. J Pharm Sci 2000;89:892-900.
52. Vanbever R, Prausnitz MR, Preat V. Macromolecules as novel transdermal transport enhancers for skin electroporation. Pharm Res 1997;14:638-644.
53. 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;49:11-20.
54. Chan SY, Po ALW. Prodrugs for dermal delivery. Int J Pharm 1989;55:1-16.
55. Fang JY, Leu YL. Prodrug strategy for enhancing drug delivery via skin. Curr Drug Discov Tech 2006;3:211-224.
56. Sloan KB, Wasdo S. Designing for topical delivery: Prodrugs can make the difference. Med Res Rev 2003;23:763-793.
57. Bonina FP, Montenegro L, de Caprariis P, Bousquet E, Tirendi S. 1-Alkylazacycloalkan-2-one esters as prodrugs of indomethacin for improved delivery through human skin. Int J Pharm 1991;77:21-29.
58. Bonina FP, Montenegro L, Guerrera F. Naproxen 1-alkylazacycloalkan-2-one esters as dermal prodrugs: In vitro evaluation. Int J Pharm 1993;100:99-105.
59. Bonina F, Santagati NA, Puglia C. Ketoprofen 1-alkylazacycloalkan-2-one esters as dermal prodrugs: In vivo and in vitro evaluations. Drug Dev Ind Pharm 2003;29:181-190.
60. Puglia C, Filosa R, Peduto A, de Caprariis P, Boatto G, Nieddu M, Santagati NA, Bonina F. Synthesis, physicochemical properties and in vitro permeation studies of new ketorolac ester derivatives. Curr Drug Deliv 2007;4:205-210.
61. Bonina FP, Montenegro L, Trapani G, Franco M, Liso G. In vitro evaluation of N-acyllactam esters of indomethacin as dermal prodrugs. Int J Pharm 1995;124:45-51.
62. Kanikkannan N, Kandimalla K, Lamba SS, Singh M. Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery. Curr Med Chem 2000;7:593-608.
63. Hrabalek A, Dolezal P, Sklubalova Z, Farsa O, Krebs A. Transdermal penetration enhancers. Chem Listy 1999;93:107-119.
64. Hori M, Satoh S, Maibach HI. Classification of percutaneous penetration enhancers: A conceptional diagram. J Pharm Pharmacol 1990;42:71-72.
65. Lambert WJ, Kudla RJ, Holland JM, Curry JT. A biodegradable transdermal penetration enhancer based on N-(2-hydroxyethyl)-2-pyrrolidone. I. Synthesis and characterization. Int J Pharm 1993;95:181-192.
66. Jessy S, Shripad M, Mansi S. Transdermal penetration enhancers. Curr Drug Ther 2007;2:133-142.
67. Pfister WR, Hsieh DST. Permeation enhancers compatible with transdermal drug delivery systems. Part I: Selection and formulation considerations. Pharm Tech 1990;14:132-140.
68. Walker RB, Smith EW. The role of percutaneous penetration enhancers. Adv Drug Deliv Rev 1996;18:295-301.
69. Hadgraft J. Passive enhancement strategies in topical and transdermal drug delivery. Int J Pharm 1999;184:1-6.
70. Williams AC, Barry BW. Chemical permeation enhancement. In: Touitou E, Barry BW, editors. Enhancement in drug delivery. Boca Raton: CRC Press; 2007. pp 233-254.
71. Anigbogu ANC, Williams AC, Barry BW, Edwards HGM. Fourier transform Raman spectroscopy of interactions between the penetration enhancer dimethyl sulfoxide and human stratum corneum. Int J Pharm 1995;125:265-282.
72. Tang-Liu DDS, Richman JB, Weinkam RJ, Takruri H. Effects of four penetration enhancers on corneal permeability of drugs in vitro. J Pharm Sci 1994;83:85-90.
73. Jagat S, Mckay D. Topical nail formulation comprising antifungal, antiinflammatory, anticancer and/or antipsoriatic agents, and penetration enhancers selected from fatty acids or Azone-related compounds. PCT Int Appl 2007; WO 2007/098591 A2.
74. Kim N, El-Khalili M, Henary MM, Strekowski L, Michniak BB. Percutaneous penetration enhancement activity of aromatic S, S-dimethyliminosulfuranes. Int J Pharm 1999;187:219-229.
75. Kanikkannan N, Singh M. Skin permeation enhancement effect and skin irritation of saturated fatty alcohols. Int J Pharm 2002;248:219-228.
76. Andega S, Kanikkannan N, Singh M. Comparison of the effect of fatty alcohols on the permeation of melatonin between porcine and human skin. J Control Release 2001;77:17-25.
77. Herai H, Gratieri T, Thomazine JA, Bentley MV, Lopez RF. Doxorubicin skin penetration from monoolein-containing propylene glycol formulations. Int J Pharm 2007;329:88-93.
78. Godwin DA, Player MR, Sowell JW, Michniak BB. Synthesis and investigation of urea compounds as transdermal penetration enhancers. Int J Pharm 1998;167:165-175.
79. Michniak BB, Player MR, Fuhrman LC, Christensen CA, Chapman JM, Jr, Sowell JW. In vitro evaluation of a series of Azone analogs as dermal penetration enhancers. III. Acyclic amides. Int J Pharm 1994;110:231-239.
80. Sasaki H, Kojima M, Mori Y, Nakamura J, Shibasaki J. Enhancing effect of pyrrolidone derivatives on transdermal penetration of 5-fluorouracil, triamcinolone acetonide, indomethacin and flurbiprofen. J Pharm Sci 1991;80:533-538.
81. Okamoto H, Hashida M, Sezaki H. Structure-activity relationship of 1-alkyl or 1-alkenylazacycloalkanone derivates as percutaneous penetration enhancers. J Pharm Sci 1988;77:418-424.
82. Zhou X, Xu J, Yao K, Liu D, Wang L, Wang X, Yang X, Liu Y, Fang Y. Interaction of 1-dodecyl-azacycloheptan-2-one with mouse stratum corneum. J Biomater Sci Polym Ed 2005;16:563-574.
83. Ozawa Y, Yamahira T, Sunada H, Nadai T. Influence of fatty acid-alcohol esters on percutaneous absorption of hydrocortisone butyrate propionate. Chem Pharm Bull 1988;36:2145-2151.
84. Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Adv Colloid Interface Sci 1988;36:2145-2151.
85. Sato K, Sugibayashi K, Morimoto Y. Effect and mode of action of aliphatic esters on the in vitro skin permeation of nicorandil. Int J Pharm 1988;43:31-40.
86. Babu RJ, Singh M, Kanikkannan N. Fatty alcohols and fatty acids. In: Smith EW, Maibach HI, editors. Percutaneous penetration enhancers. Boca Raton: CRC Press; 2006. pp 137-158.
87. Yeager JL, Buyuktimkin N, Buyuktimkin S. Prostaglandin compositions and methods of treatment for male erectile dysfunction. WO 03022310 A1; 2003.
88. Michniak BB, Player MR, Godwin DA, Phillips CA, Sowell JW. In vitro evaluation of a series of Azone analogs as dermal penetration enhancers: IV. Amines. Int J Pharm 1995;116:201-209.
89. Fincher TK, Yoo SD, Player MR, Sowell JW, Michniak BB. In vitro evaluation of a series of N-dodecanoyl-L-amino acid methyl esters as dermal penetration enhancers. J Pharm Sci 1996;85:920-923.
90. Tenjarla SN, Kasina R, Puranajoti P, Omar MS, Harris WT. Synthesis and evaluation of N-acetylprolinate esters. Novel skin penetration enhancers. Int J Pharm 1999;192:147-158.
91. Vavrova K, Hrabalek A, Dolezal P, Holas T, Zbytovska J. L-Serine and glycine based ceramide analogs as transdermal permeation enhancers: Polar head size and hydrogen bonding. Bioorg Med Chem Lett 2003;13:2351-2353.
92. Hrabalek A, Vavrova K, Dolezal P, Machacek M. Esters of 6-aminohexanoic acid as skin permeation enhancers: The effect of branching in the alkanol moiety. J Pharm Sci 2005;94:1494-1499.
93. Hrabalek A, Dolezal P, Vavrova K, Zbytovska J, Holas T, Klimentova J, Novotny J. Synthesis and enhancing effect of Transkarbam 12 on the transdermal delivery of theophylline, clotrimazole, flobufen, and griseofulvin. Pharm Res 2006;23:912-919.
94. Klimentova J, Kosak P, Vavrova K, Holas T, Novotny J, Hrabalek A. Transkarbams with terminal branching as transdermal permeation enhancers. Bioorg Med Chem Lett 2008;18:1712-1715.
95. Buyuktimkin S, Buyuktimkin N, Rytting JH. Synthesis and enhancing effect of dodecyl 2-(N, N-dimethylamino)propionate on the transepidermal delivery of indomethacin, clonidine, and hydrocortisone. Pharm Res 1993;10:1632-1637.
96. Turunen TM, Buyuktimkin S, Buyuktimkin N, Urtti A, Paronen P, Rytting JH. Enhanced delivery of 5-fluorouracil through shed snake skin by two new transdermal penetration enhancers. Int J Pharm 1993;92:89-95.
97. Godwin DA, Michniak BB. Influence of drug lipophilicity on terpenes as transdermal penetration enhancers. Drug Dev Ind Pharm 1999;25:905-915.
98. Williams AC, Barry BW. Terpenes and the lipid-protein-partitioning theory of skin penetration enhancement. Pharm Res 1991;8:17-24.
99. Sapra B, Jain S, Tiwary AK. Percutaneous permeation enhancement by terpenes: Mechanistic view. AAPS J 2008;10:120-132.
100. Rizwan M, Aqil M, Ahad A, Sultana Y, Ali MM. Transdermal delivery of valsartan: I. Effect of various terpenes. Drug Dev Ind Pharm 2008;34:618-626.
101. Zhao L, Fang L, Xu Y, Liu S, He Z, Zhao Y. Transdermal delivery of penetrants with differing lipophilicities using O-acylmenthol derivatives as penetration enhancers. Eur J Pharm Biopharm 2008;69:199-213.
102. Negishi J, Takayama K, Higashiyama K, Chida Y, Isowa K, Nagai T. Promoting effect of O-alkylmenthol and O-acylmenthol derivatives on the percutaneous absorption of ketoprofen in rats. STP Pharma Sci 1995;5:156-161.
103. Kear CL, Yang J, Godwin DA, Felton LA. Investigation into the mechanism by which cyclodextrins influence transdermal drug delivery. Drug Dev Ind Pharm 2008;34:692-697.
104. Masson M, Loftsson T, Masson G, Stefansson E. Cyclodextrins as permeation enhancers: Some theoretical evaluations and in vitro testing. J Control Release 1999;59:107-118.
105. Nokhodchi A, Shokri J, Dashbolaghi A, Hassan-Zadeh D, Ghafourian T, Barzegar-Jalali M. The enhancement effect of surfactants on the penetration of lorazepam through rat skin. Int J Pharm 2003;250:359-369.
106. Shokri J, Nokhodchi A, Dashbolaghi A, Hassan-Zadeh D, Ghafourian T, Barzegar-Jalali M. The effect of surfactants on the skin penetration of diazepam. Int J Pharm 2001;228:99-107.
107. Carelli V, Di Colo G, Nannipieri E, Serafini MF. Bile acids as enhancers of steroid penetration through excised hairless mouse skin. Int J Pharm 1993;89:81-89.
108. Shaikh IM, Jadhav KR, Kadam VJ, Pisal SS. Lecithin organogels as a drug delivery system: A review. Drug Deliv Technol 2007;7:60-66.
109. Sugibayashi K, Nemoto M, Morimoto Y. Effect of several penetration enhancers on the percutaneous absorption of indomethacin in hairless rats. Chem Pharm Bull 1988;36:1519-1528.
110. Michniak BB, Chapman JM, Seyda KL. Facilitated transport of two model steroids by esters and amides of clofibric acid. J Pharm Sci 1993;82:214-219.
111. Akimoto T, Nagase Y. Novel transdermal drug penetration enhancer: Synthesis and enhancing effect of alkyldisiloxane compounds containing glucopyranosyl group. J Control Release 2003;88:243-252.
112. Aoyagi T, Akimoto T, Nagase Y. Novel silicones for transdermal therapeutic system. 4. Modified route to prepare oligo(dimethyl siloxane) containing a cationic end-group, and its property as transdermal penetration enhancer. Makromol Chem 1992;193:2821-2828.
113. Fang JY, Fang CL, Hong CT, Chen HY, Lin TY, Wei HM. Capsaicin and nonivamide as novel skin permeation enhancers for indomethacin. Eur J Pharm Sci 2001;12:195-203.
114. Tsai JC, Guy RH, Thornfeldt CR, Feingold KR, Elias PM. Metabolic approaches to enhance transdermal drug delivery. 1. Effect of lipid synthesis inhibitors. J Pharm Sci 1996;85:643-648.
115. Patil S, Singh P, Szolar-Platzer C, Maibach H. Epidermal enzymes as penetration enhancers in transdermal drug delivery? J Pharm Sci 1996;85:249-252.
116. Venuganti VVK, Perumal OP. Poly(amidoamine) dendrimers as skin penetration enhancers: Influence of charge, generation, and concentration. J Pharm Sci 2009;98:2345-2356.
117. Michniak BB, Player MR, Godwin DA, Sowell JW. Investigation of enhancer structure activity relationships in congeners of 2-(1-nonyl)-1, 3-dioxolane. Drug Deliv 1995;2:117-122.
118. Barry BW. Mode of action of penetration enhancers in human skin. J Control Release 1987;6:85-97.
119. Walters KA, Brain KR, Green DM, James VJ, Watkinson AC, Sands RH. Comparison of the transdermal delivery of estradiol from two gel formulations. Maturitas 1998;29:189-195.
120. Barry BW. Lipid-protein-partitioning theory of skin penetration enhancement. J Control Release 1991;15:237-248.
121. Menon GK, Lee SH, Roberts MS. Ultrastructural effects of some solvents and vehicles on the stratum corneum and other skin components: Evidence for an "extended mosaic-partitioning model of the skin barrier". In: Roberts MS, Walters KA, editors. Dermal absorption and toxicity assessment. New York: Marcel Dekker; 1998. pp 727-751.
122. Williams AC, Barry BW. Skin absorption enhancers. Crit Rev Ther Drug Carrier Syst 1992;9:305-353.
123. Ibrahim SA, Li SK. Chemical enhancer solubility in human stratum corneum lipids and enhancer mechanism of action on stratum corneum lipid domain. Int J Pharm 2010;383:89-98.
124. Moser K, Kriwet K, Naik A, Kalia YN, Guy RH. Passive skin penetration enhancement and its quantification in vitro. Eur J Pharm Biopharm 2001;52:103-112.
125. Ongpipattanakul B, Burnette RR, Potts RO, Francoeur ML. Evidence that oleic acid exists in a separate phase within stratum corneum lipids. Pharm Res 1991;8:350-354.
126. Zheng T, Hopfinger AJ, Esposito EX, Liu J, Tseng YJ. Membrane-interaction quantitative structures-activity relationship (MI-QSAR) analyses of skin penetration enhancers. J Chem Inf Model 2008;48:1238-1256.
127. Menczel EM. Delipidization of the cutaneous permeability barrier and percutaneous penetration. In: Smith EW, Maibach HI, editors. Percutaneous penetration enhancers. Boca Raton: CRC Press; 1995. pp 383-392.
128. Abraham MH. Scales of solute hydrogen-bonding: Their construction and application to physicochemical and biochemical processes. Chem Soc Rev 1993;22:73-83.
129. Abraham MH, Chadha HS, Mitchell RC. The factors that influence skin penetration of solutes. J Pharm Pharmacol 1995;47:8-16.
130. Potts RO, Guy RH. A predictive algorithm for skin permeability: The effects of molecular size and hydrogen bond activity. Pharm Res 1995;12:1628-1633.
131. Roberts MS, Pugh WJ, Hadgraft J. Epidermal permeability: Penetrant structure relationships. 2. The effect of H-bonding groups in penetrants on their diffusion through the stratum corneum. Int J Pharm 1996;132:23-32.
132. Hadgraft J, Peck J, Williams DG, Pugh WJ, Allan G. Mechanisms of action of skin penetration enhancers/retarders: Azone and analogs. Int J Pharm 1996;141:17-25.
133. Mendelsohn R, Moore DJ. Vibrational spectroscopic studies of lipid domains in biomembranes and model systems. Chem Phys Lipids 1998;96:141-157.
134. Corbe E, Laugel C, Yagoubi N, Baillet A. Role of ceramide structure and its microenvironment on the conformational order of model stratum corneum lipids mixtures: An approach by FTIR spectroscopy. Chem Phys Lipids 2007;146:67-75.
135. Guillard EC, Tfayli A, Laugel C, Baillet-Guffroy A. Molecular interactions of penetration enhancers within ceramides organization: A FTIR approach. Eur J Pharm Sci 2009;36:192-199.
136. Karande P, Mitragotri S. High throughput screening of transdermal formulations. Pharm Res 2002;19:655-660.
137. Karande P, Jain A, Mitragotri S. Discovery of transdermal penetration enhancers by high-throughput screening. Nat Biotechnol 2004;22:192-197.
138. Rowat AC, Kitson N, Thewalt JL. Interactions of oleic acid and model stratum corneum membranes as seen by 2H NMR. Int J Pharm 2006;307:225-231.
139. Bouwstra JA, Peschier LJC, Brussee J, Bodde HE. Effect of N-alkylazacycloheptan-2-ones including Azone on the thermal behavior of human stratum corneum. Int J Pharm 1989;52:47-54.
140. Cornwell PA, Barry BW, Bouwstra JA, Gooris GS. 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 1996;127:9-26.
141. Thong HY, Zhai H, Maibach HI. Percutaneous penetration enhancers: An overview. Skin Pharmacol Physiol 2007;20:272-282.
142. Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev 2004;56:603-618.
143. Magnusson BM, Walters KA, Roberts MS. Veterinary drug delivery: Potential for skin penetration enhancement. Adv Drug Deliv Rev 2001;50:205-227.
144. Barry BW. Breachin the skin's barrier to drugs. Nat Biotechnol 2004;22:165-167.
145. Forslind B. A domain mosaic model of the skin barrier. Acta Dermatol-Venereol 1994;74:1-6.
146. Rajadhyaksha VJ. Novel N-bis-azacyclopentan-2-onyl alkanes. U.S. Patent 3, 989, 815; 1976.
147. Hou SY, Flynn GL. Influences of 1-dodecylazacycloheptan-2-one on permeation of membranes by weak electrolytes. 1. Theoretical analysis of weak electrolyte diffusion through membranes and studies involving silicone rubber membranes. J Pharm Sci 1997;86:85-91.
148. Afouna MI, Fincher TK, Zaghloul AAA, Reddy IK. Effect of Azone upon the in vivo antiviral efficacy of cidofovir or acyclovir topical formulations in treatment/prevention of cutaneous HSV-1 infections and its correlation with skin target site free drug concentration in hairless mice. Int J Pharm 2003;253:159-168.
149. Lopez-Cervantes M, Marquez-Mejia E, Cazares-Delgadillo J, Quintanar-Guerrero D, Ganem-Quintanar A, Angeles-Anguiano E. Chemical enhancers for the absorption of substances through the skin: Laurocapram and its derivatives. Drug Dev Ind Pharm 2006;32:267-286.
150. Hoogstraate AJ, Verhoef J, Brussee J, Ijzerman AP, Spies F, Bodde HE. Kinetics, ultrastructural aspects and molecular modeling of transdermal peptide flux enhancement by N-alkylazacycloheptanones. Int J Pharm 1991;76:37-47.
151. Lewis D, Hadgraft J. Mixed monolayers of dipalmitoylphosphatidylcholine with Azone or oleic acid at the air-water interface. Int J Pharm 1990;65:211-218.
152. Pascher I. Molecular arrangements in sphingolipids. Conformation and hydrogen bonding of ceramides and their implication on membrane stability and permeability. Biochim Biophys Acta 1976;455:433-451.
153. Jackson M, Johnston DS, Chapman D. Differential scanning calorimetric and Fourier transform infrared spectroscopic investigations of cerebroside polymorphism. Biochim Biophys Acta 1988;944:497-506.
154. Johnston DS, Chapman D. A calorimetric study of the thermotropic behaviour of mixtures of brain cerebrosides with other brain lipids. Biochim Biophys Acta 1988;939:603-614.
155. Wiedmann TS, Salmon A. Thermotropic phase properties of the hydroxyceramide/cholesterol system. Lipids 1991;26:364-368.
156. Mizushima H, Fukasawa J, Suzuki T. Thermotropic behavior of stratum corneum lipids containing a pseudoceramide. Lipids 1995;30:327-332.
157. Hadgraft J, Pugh WJ. The selection and design of topical and transdermal agents. A review. J Investig Dermatol Symp Proc 1998;3:131-135.
158. Pilgram GSK, van der Meulen J, Gooris GS, Koerten HK, Bouwstra JA. The influence of two azones and sebaceous lipids on the lateral organization of lipids isolated from human stratum corneum. Biochim Biophys Acta Biomembr 2001;1511:244-254.
159. Ponec M, Haverkort M, Soei YL, Kempenaar J, Brussee J, Bodde H. Toxicity screening of N-alkylazacycloheptan-2-one derivatives in cultured human skin cells: Structure-toxicity relationships. J Pharm Sci 1989;78:738-741.
160. Minaskanian G, Peck JV. Azocycloalkane, -ketone, and -thione derivatives as penetration enhancers for transdermal delivery of systemic agents. PCT Int Appl 1988; WO 88 02626 A1.
161. Michniak BB, Player MR, Fuhrman LC, Christensen CA, Chapman JM, Sowell JW. In vitro evaluation of a series of Azone analogs as dermal penetration enhancers. II. (Thio)amides. Int J Pharm 1993;94:203-210.
162. Singh J. Transdermal drug delivery formulation comprising an organic sulfoxide, a fatty acid ester, a fatty acid, and Azone-related compound. WO 2007016766 A1; 2007.
163. Minaskanian G, Peck JV. Penetration enhancers for transdermal delivery of systemic agents. U.S. Patent 5, 142, 044; 1992.
164. Peck JV, Minaskanian G. Use of azacycloalkanes as penetration enhancers for pharmaceutical and agrochemical preparations. WO 8704594 A1; 1987.
165. Michniak BB, Player MR, Chapman JM, Sowell JW. In vitro evaluation of a series of Azone analogs as dermal penetration enhancers I. Int J Pharm 1993;91:85-93.
166. Yamashita F, Toshioka T, Koyama Y, Okamoto H, Sezaki H, Hashida M. Analysis of skin penetration enhancement based on a two-layer skin diffusion model with polar and nonpolar routes in the stratum corneum: Dose-dependent effect of 1-geranylazacycloheptan-2-one on drugs with different lipophilicities. Biol Pharm Bull 1993;16:690-697.
167. Okamoto H, Muta K, Hashida M, Sezaki H. Percutaneous penetration of acyclovir through excised hairless mouse and rat skin: Effect of vehicle and percutaneous penetration enhancers. Pharm Res 1990;7:64-68.
168. Michniak BB, Player MR, Godwin DA, Lockhart CC, Sowell JW. In vitro evaluation of Azone analogs as dermal penetration enhancers: V. Miscellaneous compounds. Int J Pharm 1998;161:169-178.
169. Minaskanian G, Peck JV. Topical compositions comprising 1-oxo- or thiohydrocarbyl-substituted azacycloalkanes as penetration enhancers. PCT Int Appl 1989; WO 89 02735 A1.
170. Peck JV, Minaskanian G. Penetration enhancers for transdermal delivery of systemic agents. U.S. Patent 4, 879, 275; 1989.
171. Mirejovsky D, Takruri H. Dermal penetration enhancement profile of hexamethylenelauramide and its homologues: In vitro versus in vivo behavior of enhancers in the penetration of hydrocortisone. J Pharm Sci 1986;75:1089-1093.
172. Peck JV, Minaskanian G. Carboxylic acid derivatives as transdermal penetration enhancers. U.S. Patent 5, 472, 946; 1995.
173. Michniak BB, Player MR, Sowell JW. Synthesis and in vitro transdermal penetration enhancing activity of lactam N-acetic acid esters. J Pharm Sci 1996;85:150-154.
174. Kim N, El-Kattan AF, Asbill CS, Kennette RJ, Sowell JW, Latour R, Michniak BB. Evaluation of derivatives of 3-(2-oxo-1-pyrrolidine)hexahydro-1H-azepin-2-one as dermal penetration enhancers: Side chain length variation and molecular modeling. J Control Release 2001;73:183-196.
175. Quan DY, Higuchi RI, Takayama K, Higashiyama K, Nagai T. Enhancing effect of piperidone derivatives on the percutaneous absorption of indomethacin. Drug Des Deliv 1990;6:61-71.
176. Michniak BB, Player MR, Chapman JM, Jr, Sowell JW. Azone analogues as penetration enhancers: Effect of different vehicles on hydrocortisone acetate skin permeation and retention. J Control Release 1994;32:147-154.
177. Peck JV, Minaskanian G. Morpholine and piperazine derivatives as penetration enhancers for transdermal delivery of systemic agents. EP 268222 A2; 1988.
178. Takakura I, Yamakawa A, Kitayama I, Takamichi A. Transdermal preparations containing N-substituted morpholines. JP 02059528; 1990.
179. Chamber O, Thelin B. Morpholines and piperidines as transdermal and transmucosal drug delivery enhancers. WO 2008139170 A2; 2008.
180. Addy M, Moran J, Newcombe RG. Meta-analyses of studies of 0.2% delmopinol mouth rinse as an adjunct to gingival health and plaque control measures. J Clin Periodontol 2007;34:58-65.
181. 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;115:85-93.
182. Ren C, Fang L, Li T, Wang M, Zhao L, He Z. Effect of permeation enhancers and organic acids on the skin permeation of indapamide. Int J Pharm 2008;350:43-47.
183. Rhee YS, Huh JY, Park CW, Nam TY, Yoon KR, Chi SC, Park ES. Effects of vehicles and enhancers on transdermal delivery of clebopride. Arch Pharm Res 2007;30:1155-1161.
184. Furuishi T, Oda S, Saito H, Fukami T, Suzuki T, Tomono K. Effect of permeation enhancers on the in vitro percutaneous absorption of pentazocine. Biol Pharm Bull 2007;30:1350-1353.
185. Yoneto K, Li SK, Higuchi WI, Shimabayashi S. Influence of the permeation enhancers 1-alkyl-2-pyrrolidones on permeant partitioning into the stratum corneum. J Pharm Sci 1998;87:209-214.
186. Yoneto K, Ghanem AH, Higuchi WI, Peck KD, Li SK. Mechanistic studies of the 1-alkyl-2-pyrrolidones as skin permeation enhancers. J Pharm Sci 1995;84:312-317.
187. Rachakonda VK, Yerramsetty KM, Madihally SV, Robinson RL, Gasem KAM. Screening of chemical penetration enhancers for transdermal drug delivery using electrical resistance of skin. Pharm Res 2008;25:2697-2704.
188. Godwin DA, Michniak BB, Player MR, Sowell JW. Transdermal and dermal enhancing activity of pyrrolidinones in hairless mouse skin. Int J Pharm 1997;155:241-250.
189. Yano T, Higo N, Furukawa K, Tsuji M, Noda K, Otagiri M. Evaluation of a new penetration enhancer 1-[2-(decylthio)ethyl]azacyclopentan-2-one. J Pharmacobiodyn 1992;15:527-533.
190. Minaskanian G, Peck JV. Penetration enhancers for transdermal delivery of systemic agents. U.S. Patent 5, 444, 075; 1995.
191. Alexander J, Higuchi T. Pyroglutamic acid esters used as dermal penetration enhancers for drugs. U.S. Patent 4, 847, 250; 1989.
192. Sasaki H, Kojima M, Mori Y, Nakamura J, Shibasaki J. Enhancing effect of pyrrolidone derivatives on transdermal drug delivery I. Int J Pharm 1988;44:15-24.
193. Feldkamp JR, Koenig DW, Wenzel SW, Joseph WR. Transdermal delivery of oleocanthal for relief of inflammation. WO 2008001240 A2; 2008.
194. Aoyagi T, Tadenuma R, Nagase Y. Novel silicones for transdermal therapeutic system. 6. Preparation of oligodimethylsiloxane containing 2-pyrrolidone moiety as a terminal group and its enhancing effect on transdermal drug penetration. Macromol Chem Phys 1996;197:677-686.
195. Brychtova K, Jampilek J, Opatrilova R, Raich I, Farsa O, Csollei J. Synthesis, physico-chemical properties and penetration activity of alkyl-6-(2, 5-dioxopyrrolidin-1-yl)-2-(2-oxopyrrolidin-1-yl)hexanoates as potential transdermal penetration enhancers. Bioorg Med Chem 2010;18:73-79.
196. Brychtova K, Dittrichova S, Slaba B, Placek L, Opatrilova R, Jampilek J, Csollei J. Synthesis of esters of 6-(2, 5-dioxopyrrolidin-1-yl)-2-(morpholin-4-yl)hexanoic acid as potential transdermal penetration enhancers. Proceedings of the 13th International Electronic Conference on Synthetic Organic Chemistry (ECSOC-13), November 1-30, 2009, c010, http://www.usc.es/congresos/ecsoc/13 8 http://www.sciforum.net/presentation/210. Seijas JA, Vazquez-Tato MP, editors. CD-ROM edition. Basel: MDPI; 2009.
197. Ni N, El-Sayed MM, Sanghvi T, Yalkowsky SH. Estimation of the effect of NaCl on the solubility of organic compounds in aqueous solutions. J Pharm Sci 2000;89:1620-1625.
198. Katz M, Ben-Shlush I, Kolusheva S, Jelinek R. Rapid colorimetric screening of drug interaction and penetration through lipid barriers. Pharm Res 2006;23:580-588.
199. Fang JY, Tsai TH, Hung CF, Wong WW. Development and evaluation of the essential oil from Magnolia fargesii for enhancing the transdermal absorption of theophylline and cianidanol. J Pharm Pharmacol 2004;56:1493-1500.
200. Sloan KB, Beall HD, Taylor HE, Getz JJ, Villaneuva R, Nipper R, Smith K. Transdermal delivery of theophylline from alcohol vehicles. Int J Pharm 1998;171:185-193.
201. Franz TJ. Percutaneous absorption on the relevance of in vitro data. J Invest Dermatol 1975;64:190-195.
202. Jacobi U, Kaiser M, Toll R, Mangelsdorf S, Audring H, Otberg N, Sterry W, Lademann J. Porcine ear skin: An in vitro model for human skin. Skin Res Technol 2007;13:19-24.
203. Sekkat N, Kalia YN, Guy RH. Biophysical study of porcine ear skin in vitro and its comparison to human skin in vivo. J Pharm Sci 2002;91:2376-2381.
204. Herkenne C, Naik A, Kalia YN, Hadgraft J, Guy RH. Pig ear skin ex vivo as a model for in vivo dermatopharmacokinetic studies in man. Pharm Res 2006;23:1850-1856.
205. Meyer W, Schwarz K, Neurand K. The skin of domestic mammals as a model for the human skin, with special reference to the domestic pig. Curr Probl Dermatol 1978;7:39-52.
206. Wilkinson SC, Maas WJM, Nielsen JB, Greaves LC, Sandt JJM, Williams FM. Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies. Int Arch Occup Environ Health 2006;79:405-413.
207. Bronaugh RL, Maibach HI. In vitro percutaneous absorption: principles, fundamentals, and applications. Boca Raton: CRC Press; 1991.
208. Crutcher W, Maibach HI. The effect of perfusion rate on in vitro percutaneous penetration. J Invest Dermatol 1969;53:264-269.
209. Reifenrath WG, Lee B, Wilson DR, Spencer TS. A comparison of in vitro skin-penetration cells. J Pharm Sci 1994;83:1229-1233.
210. Hatanaka T, Shimoyama M, Sugibayashi K, Morimoto Y. Effect of vehicle on the skin permeability of drugs: Polyethylene glycol 400-water and ethanol-water binary solvents. J Control Release 1993;23:247-260.
211. Drakulic BJ, Juranic IO, Eric S, Zloh M. Role of complexes formation between drugs and penetration enhancers in transdermal delivery. Int J Pharm 2008;363:40-49.
212. Karande P, Jain A, Arora A, Ho MJ, Mitragotri S. Synergistic effects of chemical enhancers on skin permeability: A case study of sodium lauroylsarcosinate and sorbitan monolaurate. Eur J Pharm Sci 2007;31:1-7.
213. Bouwstra JA, Gooris GS, Brussee J, Salomons-de Vries MA, Bras W. The influence of alkyl-azones on the ordering of the lamellae in human stratum corneum. Int J Pharm 1992;79:141-148.
214. Brain KA, Walters KA. In: Walters KA, Hadgraft J. editors. Pharmaceutical skin penetration enhancement. New York: Marcel Dekker; 1993. pp 389-416.
215. Morimoto K, Tojima H, Haruta T, Suzuki M, Kakemi M. Enhancing effects of unsaturated fatty acids with various structures on the permeation of indomethacin through rat skin. J Pharm Pharmacol 1996;48:1133-1137.
216. Golden GM, McKie JE, Potts RO. Role of stratum corneum lipid fluidity in transdermal drug flux. J Pharm Sci 1987;76:25-28.
217. Tanojo H, Bouwstra JA, Junginger HE, Bodde HA. In vitro human skin barrier modulation by fatty acids: Skin permeation and thermal analysis studies. Pharm Res 1997;14:42-49.
218. Aungst BJ, Rogers NJ, Shefter E. Enhancement of naloxone penetration through human skin in vitro using fatty acids, fatty alcohols, surfactants, sulfoxides and amides. Int J Pharm 1986;33:225-234.
219. Carelli V, Di Colo G, Nannipieri E, Serafini MF. Enhancement effects in the permeation of Alprazolam through hairless mouse skin. Int J Pharm 1992;88:89-97.
220. Neumann D. Modeling transdermal absorption. In: Ehrhardt C, Kim KJ, editors. Drug absorption studies: In situ, in vitro and in silico models (biotechnology: pharmaceutical aspects, vol. 7). New York: Springer; 2008. pp 459-485.
221. Hadgraft J. Skin deep. Eur J Pharm Biopharm 2004;58:291-299.
222. Yamashita F, Hashida M. Mechanistic and empirical modeling of skin permeation of drugs. Adv Drug Deliv Rev 2003;55:1185-1199.
223. Neumann D, Kohlbacher O, Merkwirth C, Lengauer T. A fully computational model for predicting percutaneous drug absorption. J Chem Inf Model 2006;46:424-429.
224. Katritzky AR, Dobchev DA, Fara DC, Hur E, Tamm K, Kurunczi L, Karelson M, Varnek A, Solovev VP. Skin permeation rate as a function of chemical structure. J Med Chem 2006;49:3305-3314.
225. Degim IT. New tools and approaches for predicting skin permeability. Drug Discov Today 2006;11:517-523.
226. Pugh WJ, Wong R, Falson F, Michniak BB, Moss GP. Discriminant analysis as a tool to identify compounds with potential as transdermal enhancers. J Pharm Pharmacol 2005;57:1389-1396.
227. Iyer M, Mishra R, Han Y, Hopfinger AJ. Predicting blood-brain barrier partitioning of organic molecules using membrane-interaction QSAR analysis. Pharm Res 2002;19:1611-1621.
228. Iyer M, Zheng T, Hopfinger AJ, Tseng YJ. QSAR analyses of skin penetration enhancers. J Chem Inf Model 2007;47:1130-1149.
229. Kulkarni A, Han Y, Hopfinger AJ. Predicting Caco-2 cell permeation coefficients of organic molecules using membrane interaction QSAR analysis. J Chem Inf Comput Sci 2002;42:331-342.
230. Morimoto Y, Hatanaka T, Sugibayashi K, Omiya H. Prediction of skin permeability of drugs: Comparison of human and hairless rat skin. J Pharm Pharmacol 1992;44:634-639.
231. Bando H, Sahashi M, Mohri S, Yamashita F, Takakura Y, Hashida M. In vivo skin penetration enhancement of acyclovir by theoretical design of prodrug-enhancer combination. Int J Pharm 1996;145:103-113.
232. Manitz R, Lucht W, Strehmel K, Weiner R, Neubert R. On mathematical modeling of dermal and transdermal drug delivery. J Pharm Sci 1998;87:873-879.
233. Rim JE, Pinsky PM, van Osdol WW. Finite element modeling of coupled diffusion with partitioning in transdermal drug delivery. Ann Biomed Eng 2005;33:1422-1438.
234. Riviere JE, Brooks JD. Prediction of dermal absorption from complex chemical mixtures: Incorporation of vehicle effects and interactions into a QSPR framework. SAR QSAR Environ Res 2007;18:31-44.
235. Riviere JE, Brooks JD. Predicting skin permeability from complex chemical mixtures. Toxicol Appl Pharmacol 2005;208:99-110.
236. Bernardo FP, Saraiva PM. A theoretical model for transdermal drug delivery from emulsions and its dependence upon formulation. J Pharm Sci 2008;97:3781-3809.
237. Narishetty STK, Panchagnula R. Transdermal delivery of zidovudine: Effect of terpenes and their mechanism of action. J Control Release 2004;95:367-379.
238. Kang L, Yap CW, Lim PFC, Chen YZ, Ho PC, Chan YW, Wong GP, Chan SY. Formulation development of transdermal dosage forms: Quantitative structure-activity relationship model for predicting activities of terpenes that enhance drug penetration through human skin. J Control Release 2007;120:211-219.