Related Topic: Use of PAMPA and Artificial Membranes

  • Bálint SinkóEmail author
  • Krisztina Takács-Novák


The following paragraphs describe the options of applying artificial membranes for the prediction of transdermal penetration, focusing mostly on the PAMPA method. A model membrane of PAMPA mimicking skin penetration was first described in 2006, but the need for a more bio-mimetic system has arisen with new industrial tendencies, and a more bio-relevant system was published in 2012. Since its first publication, Skin PAMPA has already been applied by several universities and industrial groups successfully and the first articles, podium, and poster presentations have appeared. Application of the Skin PAMPA model has been extended and examples for testing of semi-solid formulations and transdermal patches are available, besides the standard solution applications.


Skin penetration Topical formulation Formulation development Formulation ranking API screening Excipient selection Penetration enhancer testing 


  1. 1.
    Bouwstra JA, Honeywell-Nguyen PL, Gooris GS, Ponec M (2003) Structure of the skin barrier and its modulation by vesicular formulations. Prog Lipid Res 42:1–36CrossRefPubMedGoogle Scholar
  2. 2.
    Sinko B, Garrigues MT, Balogh TG, Nagy KZ, Tsinman O, Avdeef A, Takacs-Novak K (2012) Skin-PAMPA: a new method for fast prediction of skin penetration. Eur J Pharm Sci 45(5):698–707CrossRefPubMedGoogle Scholar
  3. 3.
    Amidon GL, Lennernäs H, Shah VP, Crison JR (1995) A theoretical basis for a biopharmaceutical drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 12:413–420CrossRefPubMedGoogle Scholar
  4. 4.
    Kansy M, Senner F, Gubernator K (1998) Physicochemical high throughput screening: parallel artificial membrane permeability assay in the description of passive absorption processes. J Med Chem 41:1007–1010CrossRefPubMedGoogle Scholar
  5. 5.
    Avdeef A (2003) Absorption and drug development. 7. Permeability. John Wiley & Sons, Hoboken, NJCrossRefGoogle Scholar
  6. 6.
    Avdeef A, Tsinman O (2006) PAMPA—a drug absorption in vitro model: 13. Chemical selectivity due to membrane hydrogen bonding: in combo comparison of HDM-, DOPC-, and DS-PAMPA models. Eur J Pharm Sci 28:43–50CrossRefPubMedGoogle Scholar
  7. 7.
    Tsinman O, Tsinman K, Sun N, Avdeef A (2011) Physicochemical selectivity of the BBB microenvironment governing passive diffusion—matching with a porcine brain lipid extract artificial membrane permeability model. Pharm Res 28:337–363CrossRefPubMedGoogle Scholar
  8. 8.
    Ottaviani G, Martel S, Carrupt PA (2006) Parallel artificial membrane permeability assay: a new membrane for the fast prediction of passive human skin permeability. J Med Chem 49:3948–3954CrossRefPubMedGoogle Scholar
  9. 9.
    Avdeef A (2005) The rise of PAMPA. Expert Opin Drug Metab Toxicol 1:325–342CrossRefPubMedGoogle Scholar
  10. 10.
    Khan G, Frum Y, Sarheed O, Eccleston GM, Meidan VM (2005) Assessment of drug permeability distribution in two different model skins. Int J Pharm 303:81–87CrossRefPubMedGoogle Scholar
  11. 11.
    Chilcott R, Barai N, Beezer AE, Brain SI, Brown M, Bunge AL, Burgess SE, Cross S, Dalton CH, Dias M, Farinha A, Finnin BC, Gallagher SJ, Green DM, Gunt H, Gwther RL, Heard CM, Jarvis CA, Kamiyama F, Kasting GB, Ley EE, Lim ST, Mcnaughton GS, Morris A, Nazemi MH, Pellett MA, Du Plessis J, Quan YS, Raghavan SL, Roberts M, Romonchuk W, Roper CS, Schenk D, Simonsen L, Simpson A, Traversa BD, Trottet L, Watkinson A, Wilkinson SC, Williams FM, Yamamoto A, Hadgraft J (2005) Inter- and intralaboratory variation of in vitro diffusion cell measurements: an international multicenter study using quasi-standardized methods and materials. J Pharm Sci 94:632–638CrossRefPubMedGoogle Scholar
  12. 12.
    Frum Y, Eccleston GM, Meidan VM (2007) Evidence that drug flux through synthetic membranes is associated with normally distributed permeability coefficients. Eur J Pharm Biopharm 67:434–439CrossRefPubMedGoogle Scholar
  13. 13.
    Dobricic V, Markovic B, Nikolic K, Savic V, Vladimirov S, Cudina O (2014) 17b-carboxamide steroids—in vitro prediction of human skin permeability and retention using PAMPA technique. Eur J Pharm Sci 52:95–108CrossRefPubMedGoogle Scholar
  14. 14.
    Kratz JM, Schneider NFZ, Caon T, Teixeira MR, Mascarello A, Nunes RJ, Koester LS, Simoes CMO (2013) Evaluation of in vitro intestinal and cutaneous permeability of pentyl gallate. Lat Am J Pharm 32:1508–1515Google Scholar
  15. 15.
    Sinkó B, Pálfi M, Béni S, Kökösi J, Takács-Novák K (2010) Synthesis and characterization of long-chain tartaric acid diamides as novel ceramide-like compounds. Molecules 15:824–833CrossRefPubMedGoogle Scholar
  16. 16.
    Sinkó B, Kökösi J, Avdeef A, Takács-Novák K (2009) A PAMPA study of the permeability-enhancing effect of new ceramide analogues. Chem Biodivers 6:1867–1874CrossRefPubMedGoogle Scholar
  17. 17.
    Lee PH, Conradi R, Shanmugasundaram V (2010) Development of an in silico model for human skin permeation based on a Franz cell skin permeability assay. Bioorg Med Chem Lett 20:69–73CrossRefPubMedGoogle Scholar
  18. 18.
    Guy RH, Hadgraft J (2003) Transdermal drug delivery, 2nd edn. Skin absorption databases and predictive equations. Marcel Dekker, New YorkGoogle Scholar
  19. 19.
    Karadzovska D, Riviere EJ (2013) Assessing vehicle effects on skin absorption using artificial membrane assays. Eur J Pharm Sci 50(5):569–576. doi: 10.1016/jejps.2013.02.020 CrossRefPubMedGoogle Scholar
  20. 20.
    Vizserálek G, Balogh T, Takács-Novák K, Sinkó B (2014) PAMPA study of the temperature effect on permeability. Eur J Pharm Sci 53:45–49CrossRefPubMedGoogle Scholar
  21. 21.
    Clough M, Richardson N, Romanski F, Langley N, Tsinman K, Tsinman O (2013) Assessment of transdermal penetration enhancement by topical pharmaceutical excipients using skin PAMPA method. AAPS; T2267Google Scholar
  22. 22.
    Tsinman K, Tsinman O, Schalau K G, Aliyar A H, Huber O R, Loubert L G (2012) Application of skin PAMPA to differentiate between topical pharmaceutical formulations of ibuprofen. AAPS; R6058Google Scholar
  23. 23.
    Luo L, Sinko B, Tsinman K, Abdalghafor M H, Hadgraft J, Lane E M (2014) A comparison of drug permeation in the skin PAMPA model and the Franz cell model. AAPS; W5104Google Scholar
  24. 24.
    Vizserálek G, Sinkó B, Tsinman K, Takács-Novák K (2014) Developing a method for skin PAMPA to test transdermal patches. AAPS; M1237Google Scholar

Copyright information

© Springer Japan KK 2017

Authors and Affiliations

  1. 1.Pion Inc.BillericaUSA
  2. 2.Semmelweis UniversityBudapestHungary

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