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Human Native and Reconstructed Skin Preparations for In Vitro Penetration and Permeation Studies

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Percutaneous Penetration Enhancers Drug Penetration Into/Through the Skin

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Abstract

In vitro skin absorption studies are essential for dermal product development as well as in dermal risk assessment. This chapter introduces commonly used membranes for permeation and penetration studies, such as from human, animal, bioengineered, or artificial sources. In addition two basic types of experiments to investigate transdermal solute transport are discussed. In permeation studies, the substance transport through the skin is evaluated and systemic availability is addressed. In contrast penetration studies gain information on substance distribution in different skin layers, allowing the identification of substance depots in various skin layers. Furthermore, basic experimental setups for skin transport studies are addressed, e.g., finite and infinite dosing, vertical and horizontal diffusion cells, and static versus flow-through cells. Furthermore, the influence of fundamental experimental conditions on diffusion experiments, such as the choice of acceptor solution and temperature, are discussed.

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Abbreviations

Css:

Saturation concentration of solute in the vehicle

Cv:

Concentration in the vehicle

EC:

European Commission

ECETOC:

European Centre for Ecotoxicology and Toxicology of Chemicals

EDETOX:

Evaluations and predictions of dermal absorption of toxic chemicals

EEC:

European Economic Community

EFSA:

European Food Safety Authority

HaCaT:

Human adult low calcium high temperature keratinocytes

HPLC:

High-performance liquid chromato-graphy

Jpeak :

Peak flux

Jss :

Steady state flux

Jss(max) :

Maximum flux

LC:

Liquid chromatography

KP :

Apparent permeability coefficient

MS:

Mass spectrometry

NAFTA:

North American Free Trade Agreement

REACH:

Registration, Evaluation, Authorisation and Restriction of Chemicals

SC:

Stratum corneum

SCCNFP:

Scientific Committee on Cosmetic Products and Non-Food Products

SCCS:

Scientific Committee on Consumer Safety

TEWL:

Transepidermal water loss

tlag :

Lag-time

USEPA:

US Environmental Protection Agency

WHO:

World Health Organisation

References

  • Ackermann K, Lombardi Borgia S, Korting HC, Mewes KR, Schäfer-Korting M (2010) The phenion® full-thickness skin model for percutaneous absorption testing. Skin Pharmacol Physiol 23:105–112

    Google Scholar 

  • Avdeef A (2005) The rise of PAMPA. Expert Opin Drug Metab Toxicol 1:325–342

    Article  CAS  PubMed  Google Scholar 

  • Bernard FX, Barrault C, Deguercy A, De Wever B, Rosdy M (2000) Development of a highly sensitive in vitro phototoxicity assay using the SkinEthic™ reconstructed human epidermis. Cell Biol Toxicol 16:391–400

    Article  CAS  PubMed  Google Scholar 

  • Brain KR, Walters KA, Watkinson AC (1998) Investigation of skin permeation in vitro. In: Roberts M, Walters KA (eds) Dermal absorption and toxicity assessment, vol 91. Marcel Dekker, New York, pp. 161–187

    Google Scholar 

  • Bronaugh RL (2004a) Methods for in vitro percutaneous absorption. In: Zhai H, Maibach H (eds) Dermatotoxicology, 6th ed. CRC Press, New York, pp 520–526

    Google Scholar 

  • Bronaugh RL (2004b) Methods for in vitro skin metabolism studies. In: Zhai H, Maibach H (eds) Dermatotoxicology, 6th ed. CRC Press, New York, pp 622–630

    Google Scholar 

  • Bronaugh RL, Maibach HI (1985) Percutaneous absorption of nitroaromatic compounds: in vivo and in vitro studies in the human and monkey. J Invest Dermatol 84:180–183

    Article  CAS  PubMed  Google Scholar 

  • Bronaugh RL, Stewart RF (1984) Methods for in vitro percutaneous absorption studies III: hydrophobic compounds. J Pharm Sci 73:1255–1258

    Article  CAS  PubMed  Google Scholar 

  • Bronaugh RL, Stewart RF (1985) Methods for in vitro percutaneous absorption studies. IV: the flow-through diffusion cell. J Pharm Sci 74:64–67

    Article  CAS  PubMed  Google Scholar 

  • Bronaugh RL, Stewart RF, Congdon ER (1982) Methods for in vitro percutaneous absorption studies II. Animal models for human skin. Toxicol Appl Pharmacol 62:481–488

    Article  CAS  PubMed  Google Scholar 

  • Bronaugh RL, Stewart RF, Simon M (1986) Methods for in vitro percutaneous absorption studies VII: use of excised human skin. J Pharm Sci 75:1094–1097

    Article  CAS  PubMed  Google Scholar 

  • Challapalli PVN, Stinchcomb AL (2002) In vitro experiment optimization for measuring tetrahydrocannabinol skin permeation. Int J Pharm 241:329–339

    Article  CAS  PubMed  Google Scholar 

  • Dal Pozzo A, Liggeri E, Delucca C, Calabrese G (1991) Prediction of skin permeation of highly lipophilic compounds: in vitro model with a modified receptor phase. Int J Pharm 70:219–223

    Article  CAS  Google Scholar 

  • De Jager MW, Gooris GS, Dolbnya IP, Bras W, Ponec M, Bouwstra JA (2004) Novel lipid mixtures based on synthetic ceramides reproduce the unique stratum corneum lipid organization. J Lipid Res 45:923–932

    Article  PubMed  Google Scholar 

  • De Jager MW, Gooris GS, Ponec M, Bouwstra JA (2005) Lipid mixtures prepared with well-defined synthetic ceramides closely mimic the unique stratum corneum lipid phase behavior. J Lipid Res 46:2649–2656

    Article  PubMed  Google Scholar 

  • Dl G, Gooris GS, Ponec M, Bouwstra JA (2008) Two new methods for preparing a unique stratum corneum substitute. Biochim Biophys Acta Biomembranes 1778:2421–2429

    Article  Google Scholar 

  • Dreher F, Patouillet C, Fouchard F, Zanini M, Messager A, Roguet R et al (2002) Improvement of the experimental setup to assess cutaneous bioavailability on human skin models: dynamic protocol. Skin Pharmacol Appl Skin Physiol 15:31–39

    Article  CAS  PubMed  Google Scholar 

  • Dreher F, Modjtahedi BS, Modjtahedi SP, Maibach HI (2005) Quantification of stratum corneum removal by adhesive tape stripping by total protein assay in 96-well microplates. Skin Res Technol 11:97–101

    Article  CAS  PubMed  Google Scholar 

  • EC (2003a) European Commission, Health & Consumer protection directorate, directorate E, Food safety: plant health, animal health and welfare, international questions, Flufenacet 7469/VI/98, Brussels, Belgium, https://www.fluoridealert.org/wp-content/pesticides/flufenacet.eu.july.2003.pdf

    Google Scholar 

  • EC (2003b) European Commission, Health & Consumer protection directorate, directorate E, Food safety: plant health, animal health and welfare, international questions. Propineb SANCO/7574/VI/97-final, Brussels, Belgium, http://ec.europa.eu/food/fs/sfp/ph_ps/pro/eva/existing/list1-34_en.pdf

    Google Scholar 

  • EC (2003c) Directive 2003/15/EC of the European Parliament and of the Council of 27 February 2003, http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32003L0015

    Google Scholar 

  • EC (2004) Guidance on dermal absorption, Sanco/22s2/2000rev.7, European Commission, Brussels, Belgium, http://ec.europa.eu/food/plant/docs/pesticides_ppp_app-proc_guide_tox_dermal-absorp-2004.pdf

    Google Scholar 

  • EC 1907/2006 (2006) Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), European Commission, Brussels, Belgium, http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=uriserv:OJ.L_.2006.396.01.0001.01.ENG

    Google Scholar 

  • ECETOX (1993) ECETOC (European Centre for Ecotoxicology and Toxicology of Chemicals), Percutaneous absorption. Monograph 020, ECETOC, Brussels, Belgium, http://www.ecetoc.org/publications/monographs/

    Google Scholar 

  • EDETOX (2004) Evaluations and predictions of dermal absorption of toxic chemicals, Final report for dissemination, Faith M. Williams, https://ec.europa.eu/research/quality-of-life/ka4/pdf/report_edetox_en.pdf

    Google Scholar 

  • EEC (1976) Council directive on the approximation of laws of the Member States relating to cosmetic products (76/768/EEC), European Commission, Brussels, Belgium

    Google Scholar 

  • EFSA (2012) Panel on Plant Protection Products and their Residues, Guidance on Dermal Absorption, EFSA Journal 10(4):2665. DOI: 10.2903/j.efsa.2012.2665 https://www.efsa.europa.eu/en/efsajournal/pub/2665

    Google Scholar 

  • Elkeeb R, Hui X, Chan H, Tian L, Maibach HI (2010) Correlation of transepidermal water loss with skin barrier properties in vitro: comparison of three evaporimeters. Skin Res Technol 16:9–15

    Article  PubMed  Google Scholar 

  • FDA (1997) U.S. Food and Drug Administration, Silver Spring, MD 20993, USA Guidance SUPAC-SS: Nonsterile Semisolid Dosage Forms; Scaling-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls; In Vitro Release Testing and In Vivo Bioequivalence Documentation. Food and Drug Administration, Silver Spring, MD 20993, USA, http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm070930.pdf

    Google Scholar 

  • Feldmann RJ, Maibach HI (1969) Percutaneous penetration of steroids in man. J Invest Dermatol 52:89–94

    Article  CAS  PubMed  Google Scholar 

  • Franz TJ (1975) Percutaneous absorption. On the relevance of in vitro data. J Invest Dermatol 64:190–195

    Article  CAS  PubMed  Google Scholar 

  • Franzen L, Windbergs M, Hansen S (2012) Assessment of near-infrared densitometry for in situ determination of the total stratum corneum thickness on pig skin: influence of storage time. Skin Pharmacol Physiol 25:249–256

    Article  CAS  PubMed  Google Scholar 

  • Grégoire S, Patouillet C, Noé C, Fossa I, Benech Kieffer F, Ribaud C (2008) Improvement of the experimental setup for skin absorption screening studies with reconstructed skin EPISKIN®. Skin Pharmacol Physiol 21:89–97

    Google Scholar 

  • Gysler A, Kleuser B, Sippl W, Lange K, Korting HC, Höltje HD et al (1999) Skin penetration and metabolism of topical glucocorticoids in reconstructed epidermis and in excised human skin. Pharm Res 16:1386–1391

    Article  CAS  PubMed  Google Scholar 

  • Hahn T, Hansen S, Neumann D, Kostka KH, Lehr CM, Muys L et al (2010) Infrared densitometry: a fast and non-destructive method for exact stratum corneum depth calculation for in vitro tape-stripping. Skin Pharmacol Physiol 23:183–192

    Article  CAS  PubMed  Google Scholar 

  • Hahn T, Selzer D, Neumann D, Kostka KH, Lehr CM, Schaefer UF (2012) Influence of the application area on finite dose permeation in relation to drug type applied. Exp Dermatol 21:233–235

    Article  CAS  PubMed  Google Scholar 

  • Haigh JM, Smith EW (1994) The selection and use of natural and synthetic membranes for in vitro diffusion experiments. Eur J Pharma Sci 2:311–330

    Article  CAS  Google Scholar 

  • Hansen S, Henning A, Naegel A, Heisig M, Wittum G, Neumann D et al (2008) In-silico model of skin penetration based on experimentally determined input parameters. Part I: experimental determination of partition and diffusion coefficients. Eur J Pharm Biopharm 68:352–367

    Article  CAS  PubMed  Google Scholar 

  • Harrison SM, Barry BW, Dugard PH (1984) Effects of freezing on human skin permeability. J Pharm Pharmacol 36:261–262

    Article  CAS  PubMed  Google Scholar 

  • Hawkins GS Jr, Reifenrath WG (1984) Development of an in vitro model for determining the fate of chemicals applied to skin. Fundam Appl Toxicol 4:S133–S144

    Article  PubMed  Google Scholar 

  • Henning A, Neumann D, Kostka KH, Lehr CM, Schaefer UF (2008) Influence of human skin specimens consisting of different skin layers on the result of in vitro permeation experiments. Skin Pharmacol Physiol 21:81–88

    Article  CAS  PubMed  Google Scholar 

  • Henning A, Schaefer UF, Neumann D (2009) Potential pitfalls in skin permeation experiments: influence of experimental factors and subsequent data evaluation. Eur J Pharm Biopharm 72:324–331

    Article  CAS  PubMed  Google Scholar 

  • Hikima T, Kaneda N, Matsuo K, Tojo K (2012) Prediction of percutaneous absorption in human using three-dimensional human cultured epidermis LabCyte EPI-MODEL. Biol Pharm Bull 35:362–368

    Article  CAS  PubMed  Google Scholar 

  • Jaeckle E, Schaefer UF, Loth H (2003) Comparison of effects of different ointment bases on the penetration of ketoprofen through heat-separated human epidermis and artificial lipid barriers. J Pharm Sci 92:1396–1406

    Article  CAS  PubMed  Google Scholar 

  • Joshi V, Brewster D, Colonero P (2012) In vitro diffusion studies in transdermal research: a synthetic membrane model in place of human skin, Drug Dev Deliv, Issue: March 2012, http://www.drug-dev.com/Main/Back-Issues/In-Vitro-Diffusion-Studies-in-Transdermal-Research-509.aspx

    Google Scholar 

  • Kalia YN, Pirot F, Guy RH (1996) Homogeneous transport in a heterogeneous membrane: water diffusion across human stratum corneum in vivo. Biophys J 71:2692–2700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kandárová H, Liebsch M, Schmidt E, Genschow E, Traue D, Spielmann H et al (2006a) Assessment of the skin irritation potential of chemicals by using the SkinEthic reconstructed human epidermal model and the common skin irritation protocol evaluated in the ECVAM skin irritation validation study. ATLA Altern Lab Anim 34:393–406

    PubMed  Google Scholar 

  • Kandárová H, Liebsch M, Spielmann H, Genschow E, Schmidt E, Traue D et al (2006b) Assessment of the human epidermis model SkinEthic RHE for in vitro skin corrosion testing of chemicals according to new OECD TG 431. Toxicol In Vitro 20:547–559

    Article  PubMed  Google Scholar 

  • Kasting GB, Miller MA (2006) Kinetics of finite dose absorption through skin 2: volatile compounds. J Pharm Sci 95:268–280

    Article  CAS  PubMed  Google Scholar 

  • Kietzmann M, Loscher W, Arens D, Maass P, Lubach D (1993) The isolated perfused bovine udder as an in vitro model of percutaneous drug absorption of dexamethasone, benzoyl peroxide, and etofenamate. J Pharmacol Toxicol Meth 30:75–84

    Article  CAS  Google Scholar 

  • Kiistala U (1968) Suction blister device for separation of viable epidermis from dermis. J Invest Dermatol 50:129–137

    Article  CAS  PubMed  Google Scholar 

  • Kligman AM, Christophers E (1963) Preperation of isolated sheets of human stratum corneum. Arch Dermatol 88:702–705

    Article  CAS  PubMed  Google Scholar 

  • Lademann J, Richter H, Schaefer UF, Blume-Peytavi U, Teichmann A, Otberg N et al (2006) Hair follicles – a long-term reservoir for drug delivery. Skin Pharmacol Physiol 19:232–236

    Article  CAS  PubMed  Google Scholar 

  • Lademann J, Richter H, Teichmann A, Otberg N, Blume-Peytavi U, Luengo J et al (2007) Nanoparticles – an efficient carrier for drug delivery into the hair follicles. Eur J Pharm Biopharm 66:159–164

    Article  CAS  PubMed  Google Scholar 

  • Lademann J, Jacobi U, Surber C, Weigmann HJ, Fluhr JW (2009) The tape stripping procedure – evaluation of some critical parameters. Eur J Pharm Biopharm 72:317–323

    Article  CAS  PubMed  Google Scholar 

  • Lee G, Parlicharla P (1986) An examination of excised skin tissues used for in vitro membrane permeation studies. Pharm Res 3:356–359

    Article  CAS  PubMed  Google Scholar 

  • Liebsch M, Traue D, Barrabas C, Spielmann H, Gerberick GF, Prevalidationof the EpiDermTM phototoxicity test; Alternatives to Animal Testing II. In: Clark D G, Lisansky SG, andMacmillan R. (ed.) COLIPA, Brussels, Belgium, pp.160–167.

    Google Scholar 

  • Magnusson BM, Anissimov YG, Cross SE, Roberts MS (2004) Molecular size as the main determinant of solute maximum flux across the skin. J Invest Dermatol 122:993–999

    Article  CAS  PubMed  Google Scholar 

  • Suhonen TM, Pasonen-Seppänen S, Kirjavainen M, Tammi M, Tammi R, Urtti A (2003) Epidermal cell culture model derived from rat keratinocytes with permeability characteristics comparable to human cadaver skin. Eur J Pharm Sci 20:107–113

    Google Scholar 

  • Melero A, Hahn TM, Schaefer UF, Schneider M (2011) In vitro human skin segmentation and drug concentration-skin depth profiles. Methods Mol Biol 763:33–50

    Google Scholar 

  • Moghimi HR, Barry BW, Williams AC (1999) Stratum corneum and barrier performance: a model lamellar structural approach. In: Bronaugh RL, Maibach H (eds) Drugs – cosmetics – mechanisms – methodology. Marcel Dekker, New York, Basel, Hong Kong, pp 515–553

    Google Scholar 

  • Moody RP (1997) Automated in Vitro Dermal Absorption (AIVDA): a new in vitro method for investigating transdermal flux. ATLA Altern Lab Anim 25:347–357

    Google Scholar 

  • Moody RP (2000) Automated In Vitro Dermal Absorption (AIVDA): predicting skin permeation of atrazine with finite and infinite (swimming/bathing) exposure models. Toxicol In Vitro 14:467–474

    Article  CAS  PubMed  Google Scholar 

  • NAFTA (2009) Detailed Review and Harmonisation of Dermal Absorption Practices – Position Paper on Use of in vitro Dermal Absorption Data in Risk Assessment. NAFTA Absorption Group, Washington, DC 20508, USA

    Google Scholar 

  • Netzlaff F, Lehr CM, Wertz PW, Schaefer UF (2005) The human epidermis models EpiSkin®, SkinEthic® and EpiDerm®: an evaluation of morphology and their suitability for testing phototoxicity, irritancy, corrosivity, and substance transport. Eur J Pharm Biopharm 60:167–178

    Google Scholar 

  • Netzlaff F, Kostka KH, Lehr CM, Schaefer UF (2006a) TEWL measurements as a routine method for evaluating the integrity of epidermis sheets in static Franz type diffusion cells in vitro. Limitations shown by transport data testing. Eur J Pharm Biopharm 63:44–50

    Article  CAS  PubMed  Google Scholar 

  • Netzlaff F, Schaefer UF, Lehr CM, Meiers P, Stahl J, Kietzmann M et al (2006b) Comparison of bovine udder skin with human and porcine skin in percutaneous permeation experiments. ATLA Altern Lab Anim 34:499–513

    CAS  PubMed  Google Scholar 

  • Netzlaff F, Kaca M, Bock U, Haltner-Ukomadu E, Meiers P, Lehr C-M et al (2007) Permeability of the reconstructed human epidermis model Episkin® in comparison to various human skin preparations. Eur J Pharm Biopharm 66:127–134

    Google Scholar 

  • OECD (2004a) Guidance Document for the Conduct of Skin Absorption Studies, OECD series on testing and assessment Nr. 28, OECD Publishing, Paris. DOI: http://dx.doi.org/10.1787/9789264078796-en

    Google Scholar 

  • OECD (2004b) Test No. 428: Skin Absorption: In Vitro Method, OECD Publishing, Paris. DOI: http://dx.doi.org/10.1787/9789264071087-en

    Google Scholar 

  • OECD (2004c) Test No. 431: In Vitro Skin Corrosion: Human Skin Model Test, OECD Publishing, Paris. DOI: http://dx.doi.org/10.1787/9789264071148-en

    Google Scholar 

  • OECD (2006) Test No. 435: In Vitro Membrane Barrier Test Method for Skin Corrosion, OECD Publishing, Paris. DOI: http://dx.doi.org/10.1787/9789264067318-en

    Google Scholar 

  • OECD (2010) Test No. 439: In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method, OECD Publishing, Paris. DOI: http://dx.doi.org/10.1787/9789264090958-en

    Google Scholar 

  • Ottaviani G, Martel S, Carrupt P-A (2006) Parallel artificial membrane permeability assay: a new membrane for the fast prediction of passive human skin permeability. J Med Chem 49:3948–3954

    Article  CAS  PubMed  Google Scholar 

  • Patzelt A, Richter H, Knorr F, Schaefer U, Lehr C-M, Dähne L et al (2011) Selective follicular targeting by modification of the particle sizes. J Control Release 150:45–48

    Article  CAS  PubMed  Google Scholar 

  • Pittermann WF, Kietzmann M (2006) Bovine Udder Skin (BUS): testing of skin compatibility an skin protection. Bovine Udder Skin (BUS): Prüfung von Hautverträglichkeit und Hautschutz 23:65–71

    Google Scholar 

  • Poet TS, McDougal JN (2002) Skin absorption and human risk assessment. Chem Biol Interact 140:19–34

    Article  CAS  PubMed  Google Scholar 

  • Prow TW, Grice JE, Lin LL, Faye R, Butler M, Becker W et al (2011) Nanoparticles and microparticles for skin drug delivery. Adv Drug Deliv Rev 63:470–491

    Article  CAS  PubMed  Google Scholar 

  • Rauma M, Boman A, Johanson G (2013) Predicting the absorption of chemical vapours. Adv Drug Deliv Rev 65:306–314

    Article  CAS  PubMed  Google Scholar 

  • Reichling J, Landvatter U, Wagner H, Kostka KH, Schaefer UF (2006) In vitro studies on release and human skin permeation of Australian tea tree oil (TTO) from topical formulations. Eur J Pharm Biopharm 64:222–228

    Article  CAS  PubMed  Google Scholar 

  • Roberts M, Cross S, Pellett M (2002) Skin transport. In:. Walters K (ed) Dermatological and trandermal formulations, vol 119. Marcel Dekker, New York, pp 89–195

    Google Scholar 

  • Rossignol MR (2005) The 7th Amendment to the Cosmetics Directive. Atla-Altern Lab Anim 33:19–22

    Google Scholar 

  • Russell LM, Guy RH (2012) Novel imaging method to quantify stratum corneum in dermatopharmacokinetic studies. Pharma Res 29:2389–2397

    Article  CAS  Google Scholar 

  • Russell C, Russell WMS (1957) An approach to human ethology. Behav Sci 2:169–200

    Article  Google Scholar 

  • Russell LM, Wiedersberg S, Begoña Delgado-Charro M (2008) The determination of stratum corneum thickness. An alternative approach. Eur J Pharm Biopharm 69:861–870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Savic S, Weber C, Tamburic S, Savic M, Müller-Goymann C (2009) Topical vehicles based on natural surfactant/fatty alcohols mixed emulsifier: the influence of two polyols on the colloidal structure and in vitro/in vivo skin performance. J Pharm Sci 98:2073–2090

    Article  CAS  PubMed  Google Scholar 

  • SCCNFP/0167/99, (2003), Final: Basic Criteria for the in vitro assessment of percutaneous absorption of cosmetic ingredients, adopted by the SCCNFP during the 8th plenary meeting of 23 June 1999. European Commission Health & Consumers, Directorate C: Public Health and Risk Assessment, Unit C7 - Risk Assessment Office: B232 B-1049, Brussels, Belgium

    Google Scholar 

  • SCCNFP/0690/03 (2003) Final: Notes of Guidance for Testing of Cosmetic Ingredients for Their Safety Evaluation, adopted by the SCCNFP during the 25th plenary meeting of 20 October 2003. European Commission Health & Consumers, Directorate C: Public Health and Risk Assessment, Unit C7 - Risk Assessment Office: B232 B-1049, Brussels, Belgium

    Google Scholar 

  • SCCS/1358/10 (2010) Basic criteria for the in vitro assessment of dermal absorption of cosmetic ingredients, doi: 10.2772/25843, European Commission, Health & Consumers Directorate C: Public Health and Risk Assessment, Unit C7 - Risk Assessment, Office: B232 B-1049 Brussels, Belgium, doi: 10.2772/25843

    Google Scholar 

  • Schaefer H, Loth H (1996) An ex vivo model for the study of drug penetration into human skin. Pharm Res 13:366

    Google Scholar 

  • Schaefer U, Hansen S, Schneider M, Luengo J, Lehr C-M (2008) Models for skin absorption and skin toxicity testing. Drug absorption studies: in situ, in vitro and in silico models. Springer, New York

    Google Scholar 

  • Schäfer-Korting M, Bock U, Gamer A, Haberland A, Haltner-Ukomadu E, Kaca M et al (2006) Reconstructed human epidermis for skin absorption testing: results of the German prevalidation study. ATLA Altern Lab Anim 34:283–294

    PubMed  Google Scholar 

  • Schäfer-Korting M, Bock U, Diembeck W, Düsing HJ, Gamer A, Haltner-Ukomadu E et al (2008) The use of reconstructed human epidermis for skin absorption testing: results of the validation study. ATLA Altern Lab Anim 36:161–187

    PubMed  Google Scholar 

  • Schreiber S, Mahmoud A, Vuia A, Rübbelke MK, Schmidt E, Schaller M et al (2005) Reconstructed epidermis versus human and animal skin in skin absorption studies. Toxicol In Vitro 19:813–822

    Article  CAS  PubMed  Google Scholar 

  • Sclafani J, Liu P, Hansen E, Cettina MG, Nightingale J (1995) A protocol for the assessment of receiver solution additive-induced skin permeability changes. An example with γ-cyclodextrin. Int J Pharm 124:213–217

    Article  CAS  Google Scholar 

  • Scott RC, Walker M, Dugard PH (1986) In vitro percutaneous absorption experiments: a technique for the production of intact epidermal membranes from rat skin. J Soc Cosm Chem Jap 37:35–41

    CAS  Google Scholar 

  • Selzer D, Schaefer UF, Lehr C-M, Hansen S (2013) Basic mathematics in skin absorption. In: Dragicevic-Curic N, Maibach HI (eds) Chemical methods in penetration enhancement. Springer, Heidelberg

    Google Scholar 

  • Semlin L, Schäfer-Korting M, Borelli C, Korting HC (2011) In vitro models for human skin disease. Drug Discov Today 16:132–139

    Article  CAS  PubMed  Google Scholar 

  • Shah VP, Flynn GL, Yacobi A, Maibach HI, Bon C, Fleischer NM et al (1998) Bioequivalence of topical dermatological dosage forms – methods of evaluation of bioequivalence. Pharm Res 15:167–171

    Article  CAS  PubMed  Google Scholar 

  • Sinkó B, Garrigues TM, Balogh GT, Nagy ZK, Tsinman O, Avdeef A et al (2012) Skin-PAMPA: a new method for fast prediction of skin penetration. Eur J Pharm Sci 45:698–707

    Article  PubMed  Google Scholar 

  • Solich P, Ogrocka E, Schaefer U (2001) Application of automated flow injection analysis to drug liberations studies with the Franz diffusion cell. Die Pharmazie 56:787–789

    CAS  PubMed  Google Scholar 

  • Solich P, Sklenarova H, Huclova J, Stafinsky D, Schaefer UF (2003) Fully automated drug liberation apparatus for semisolid preparations based on sequential injection analysis. Anal Chim Acta 499:9–16

    Article  CAS  Google Scholar 

  • Spielmann H, Müller L, Averbeck D, Balls M, Brendler-Schwaab S, Castell JV et al (2000) The second ECVAM workshop on phototoxicity testing: the report and recommendations of ECVAM workshop 42 1,2. ATLA Altern Lab Anim 28:777–814

    CAS  PubMed  Google Scholar 

  • Surber C, Smith EW (2005) The mystical effects of dermatological vehicles. Dermatology 210:157–168

    Article  PubMed  Google Scholar 

  • Surber C, Schwarb FP, Smith EW (1999) Tape-stripping technique. In: Bronaugh RL, Maibach H (eds) Percutaneous absorption: drugs-cosmetics-mechanisms-methodology, vol 97, 3rd ed. Marcel Dekker, New York, pp 395–409

    Google Scholar 

  • Swarbrick J, Lee G, Brom J (1982) Drug permeation through human skin: I. Effect of storage conditions of skin. J Invest Dermatol 78:63–66

    Article  CAS  PubMed  Google Scholar 

  • USEPA (2004) In vitro dermal absorption rate testing of certain chemicals of interest to the Occupational Safety and Heath Administration; Final rule. Fed Regist; 69(80):22402-41. https://www.gpo.gov/fdsys/pkg/FR-2004-04-26/pdf/04-9409.pdf

    Google Scholar 

  • Van De Sandt JJM, Meuling WJA, Elliott GR, Cnubben NHP, Hakkert BC (2000) Comparative in vitro-in vivo percutaneous absorption of the pesticide propoxur. Toxicol Sci 58:15–22

    Article  PubMed  Google Scholar 

  • van de Sandt JJM, van Burgsteden JA, Cage S, Carmichael PL, Dick I, Kenyon S et al (2004) In vitro predictions of skin absorption of caffeine, testosterone, and benzoic acid: a multi-centre comparison study. Regul Toxicol Pharmacol 39:271–281

    Article  PubMed  Google Scholar 

  • Veccia BE, Bunge AL (2003) Skin absorption databases and predictive equations. In: Guy R, Hadgraft J (eds) Transdermal drug delivery, vol 123, 2nd ed. Marcel Dekker, New York, pp 57–141

    Google Scholar 

  • Voegeli R, Heiland J, Doppler S, Rawlings AV, Schreier T (2007) Efficient and simple quantification of stratum corneum proteins on tape strippings by infrared densitometry. Skin Res Technol 13:242–251

    Article  CAS  PubMed  Google Scholar 

  • Wagner H, Kostka KH, Lehr CM, Schaefer UF (2000) Drug distribution in human skin using two different in vitro test systems: comparison with in vivo data. Pharm Res 17:1475–1481

    Article  CAS  PubMed  Google Scholar 

  • Wagner H, Kostka KH, Lehr CM, Schaefer UF (2001) Interrelation of permeation and penetration parameters obtained from in vitro experiments with human skin and skin equivalents. J Control Release 75:283–295

    Article  CAS  PubMed  Google Scholar 

  • Wagner H, Kostka KH, Lehr CM, Schaefer UF (2002) Correlation between stratum corneum/water-partition coefficient and amounts of flufenamic acid penetrated into the stratum corneum. J Pharm Sci 91:1915–1921

    Article  CAS  PubMed  Google Scholar 

  • Weigmann HJ, Lindemann U, Antoniou C, Tsikrikas GN, Stratigos AI, Katsambas A et al (2003) UV/VIS absorbance allows rapid, accurate, and reproducible mass determination of corneocytes removed by tape stripping. Skin Pharmacol Appl Skin Physiol 16:217–227

    Article  PubMed  Google Scholar 

  • Wertz PW (1996) The nature of the epidermal barrier: biochemical aspects. Adv Drug Deliv Rev 18:283–294

    Article  CAS  Google Scholar 

  • WHO (2006) Dermal Absorption. Environmental Health Criteria (EHC) 235, ISBN 978 92-4-157235, World Health Organization, Geneva

    Google Scholar 

  • Wilkinson SC, Mass WJM, Nielsen JB, Greaves LC, van de Sandt JJM, Williams FM (2004) Influence of skin thickness on percutaneous penetration in vitro. In: Brain KR, Walters KA (eds) Perspectives in percutaneous penetration, vol 9a. STS Publishing, Cardiff

    Google Scholar 

  • Wilkinson SC, Maas WJM, Nielsen JB, Greaves LC, van de Sandt JJM, Williams FM (2006) Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies. In Arch Occup Environ Health 79:405–413

    Article  CAS  Google Scholar 

  • Williams AC, Barry BW (2012) Penetration enhancers. Adv Drug Deliv Rev 64(Suppl):128–137

    Google Scholar 

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Authors and Affiliations

  1. Biopharmaceutics and Pharmaceutical Technology, Saarland University, Campus A 4.1, D-66123, Saarbruecken, Germany

    Ulrich F. Schaefer, D. Selzer, S. Hansen & Claus-Michael Lehr

  2. Department of Drug Delivery, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Campus E 8.1, D-66123, Saarbruecken, Germany

    S. Hansen & Claus-Michael Lehr

Authors
  1. Ulrich F. Schaefer
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  2. D. Selzer
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  3. S. Hansen
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  4. Claus-Michael Lehr
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Corresponding authors

Correspondence to Ulrich F. Schaefer or Claus-Michael Lehr .

Editor information

Editors and Affiliations

  1. Apoteka “Beograd”, Belgrade, Serbia

    Nina Dragicevic

  2. San Francisco, California, USA

    Howard I. Maibach

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Schaefer, U.F., Selzer, D., Hansen, S., Lehr, CM. (2017). Human Native and Reconstructed Skin Preparations for In Vitro Penetration and Permeation Studies. In: Dragicevic, N., I. Maibach, H. (eds) Percutaneous Penetration Enhancers Drug Penetration Into/Through the Skin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-53270-6_10

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