Pharmaceutical Research

, Volume 28, Issue 5, pp 962–977 | Cite as

Lipophilicity and Its Relationship with Passive Drug Permeation

  • Xiangli Liu
  • Bernard Testa
  • Alfred Fahr
Expert Review


In this review, we first summarize the structure and properties of biological membranes and the routes of passive drug transfer through physiological barriers. Lipophilicity is then introduced in terms of the intermolecular interactions it encodes. Finally, lipophilicity indices from isotropic solvent systems and from anisotropic membrane-like systems are discussed for their capacity to predict passive drug permeation across biological membranes such as the intestinal epithelium, the blood-brain barrier (BBB) or the skin. The broad evidence presented here shows that beyond the predictive power of lipophilicity parameters, the various intermolecular forces they encode allow a mechanistic interpretation of passive drug permeation.


lipophilicity permeation quantitative structure-permeation relationships 



absorption, distribution, metabolism and excretion


blood-brain barrier






the 1,2-dichloroethane/water system






egg phosphatidylcholine


immobilized artificial membrane


immobilized liposome chromatography


liposome electrokinetic chromatography


large multilamellar vesicles

log D

distribution coefficient

log k

capacity factor

log Kp

permeability coefficients

log P

partition coefficient


large unilamellar vesicles








stratum corneum


small unilamellar vesicles


unstirred water layer



We would like to thank Dr. Sylvio May, North Dakota State University for helpful discussions.


  1. 1.
    Stenberg P, Norinder U, Luthman K, Artursson P. Experimental and computational screening models for the prediction of intestinal drug absorption. J Med Chem. 2001;44(12):1927–37.PubMedCrossRefGoogle Scholar
  2. 2.
    Singer SJ, Nicolson GL. The fluid mosaic model of the structure of cell membranes. Science. 1972;175(23):720–31.PubMedCrossRefGoogle Scholar
  3. 3.
    Thomas G. Medicinal chemistry. An introduction. Chichester: Wiley; 2000.Google Scholar
  4. 4.
    Delattre J, Couvreur P, Puisieux F, Philippot JR, Schuber F. Les liposomes aspects technologiques, biologiques et pharmacologiques. Paris: Les Editions INSERM; 1993.Google Scholar
  5. 5.
    Lasic DD. Liposomes: from physics to applications. Amsterdam: Elsevier; 1993.Google Scholar
  6. 6.
    Tsui FC, Ojcius DM, Hubbell WL. The intrinsic pKa values for phosphatidylserine and phosphatidylethanolamine in phosphatidylcholine host bilayers. Biophys J. 1986;49(2):459–68.PubMedCrossRefGoogle Scholar
  7. 7.
    Albert A. Selective toxicity. The physico-chemical basis of therapy. London: Chapman and Hall; 1985.Google Scholar
  8. 8.
    Conradi RA, Burton PS, Borchardt RT. Physico-chemical and biological factors that influence a drug’s cellular permeability by passive diffusion. In: Pliska V, Testa B, van de Waterbeemd H, editors. Lipophilicity in drug action and toxicology. Weinheim: VCH Publishers; 1996. p. 233–52.CrossRefGoogle Scholar
  9. 9.
    Borchardt RT. Biological models to acess drug bioavailability. In: Testa B, van de Waterbeemd H, Folkers G, Guy RH, editors. Pharmacokinetic optimization in drug research: biological, physicochemical and computational strategies. Zurich: Wiley-VHCA; 2001. p. 117–26.CrossRefGoogle Scholar
  10. 10.
    Camenisch G, Folkers G, van de Waterbeemd H. Review of theoretical passive drug absorption models: historical background, recent developments and limitations. Pharm Acta Helv. 1996;71(5):309–27.PubMedGoogle Scholar
  11. 11.
    Smith DA, Jones BC, Walker DK. Design of drugs involving the concepts and theories of drug metabolism and pharmacokinetics. Med Res Rev. 1996;16(3):243–66.PubMedCrossRefGoogle Scholar
  12. 12.
    Lennernas H. Does fluid flow across the intestinal mucosa affect quantitative oral drug absorption? Is it time for a reevaluation? Pharm Res. 1995;12(11):1573–82.PubMedCrossRefGoogle Scholar
  13. 13.
    Pauletti GM, Gangwar S, Siahaan TJ, Abé J, Borchardt RT. Improvement of oral peptide bioavailability: peptidomimetics and prodrug strategies. Adv Drug Deliv Rev. 1997;27:235–56.PubMedCrossRefGoogle Scholar
  14. 14.
    Nellans HN. Mechanisms of peptide and protein absorption. Paracellular intestinal transport: modulation of absorption. Adv Drug Deliv Rev. 1991;7:339–64.CrossRefGoogle Scholar
  15. 15.
    Van Itallie CM, Holmes J, Bridges A, Gookin JL, Coccaro MR, Proctor W, et al. The density of small tight junction pores varies among cell types and is increased by expression of claudin-2. J Cell Sci. 2008;121(3):298–305.PubMedCrossRefGoogle Scholar
  16. 16.
    Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol. 2009;9(11):799–809.PubMedCrossRefGoogle Scholar
  17. 17.
    Pauletti GM, Okumu FW, Borchardt RT. Effect of size and charge on the passive diffusion of peptides across Caco-2 cell monolayers via the paracellular pathway. Pharm Res. 1997;14(2):164–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Brightman MW, Tao-Chen JH. Tight junctions of brain endothelium and epithelium. In: Pardridge WM, editor. The blood–brain barrier cellular and molecular biology. New York: Raven Press; 1993. p. 107–25.Google Scholar
  19. 19.
    Wunderli-Allenspach H. Methodologies in cell culture. In: Testa B, van de Waterbeemd H, Folkers G, Guy RH, editors. Pharmacokinetic optimization in drug research: biological, physicochemical and computational strategies. Zurich: Wiley-VHCA; 2001. p. 99–116.Google Scholar
  20. 20.
    Peters WH, Boon CE, Roelofs HM, Wobbes T, Nagengast FM, Kremers PG. Expression of drug-metabolizing enzymes and P-170 glycoprotein in colorectal carcinoma and normal mucosa. Gastroenterology. 1992;103(2):448–55.PubMedGoogle Scholar
  21. 21.
    Gottesman MM, Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem. 1993;62:385–427.PubMedCrossRefGoogle Scholar
  22. 22.
    Avdeef A. Physicochemical profiling (solubility, permeability and charge state). Curr Top Med Chem. 2001;1(4):277–351.PubMedCrossRefGoogle Scholar
  23. 23.
    Balimane PV, Chong S. Cell culture-based models for intestinal permeability: a critique. Drug Discov Today. 2005;10(5):335–43.PubMedCrossRefGoogle Scholar
  24. 24.
    Audus KL, Bartel RL, Hidalgo IJ, Borchardt RT. The use of cultured epithelial and endothelial cells for drug transport and metabolism studies. Pharm Res. 1990;7(5):435–51.PubMedCrossRefGoogle Scholar
  25. 25.
    Kramer SD, Abbott NJ, Begley DJA. Biological models to study blood brain barrier permeation. In: Testa B, van de Waterbeemd H, Folkers G, Guy RH, editors. Pharmacokinetic optimization in drug research: biological, physicochemical and computational strategies. Zurich: Wiley-VHCA; 2001. p. 127–53.CrossRefGoogle Scholar
  26. 26.
    de Boer AG, Breimer DD. Reconstitution of the blood-brain barrier in cell culture for studies of drug transport and metabolism. Adv Drug Deliv Rev. 1996;22:251–64.CrossRefGoogle Scholar
  27. 27.
    van Bree JB, de Boer AG, Danhof M, Breimer DD. Drug transport across the blood-brain barrier. I. Anatomical and physiological aspects. Pharm Weekbl Sci. 1992;14:305–10.PubMedGoogle Scholar
  28. 28.
    Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37(1):13–25.PubMedCrossRefGoogle Scholar
  29. 29.
    Hadgraft J. Skin deep. Eur J Pharm Biopharm. 2004;58(2):291–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Hadgraft J, Pugh WJ. The selection and design of topical and transdermal agents: a review. J Investig Dermatol Symp Proc. 1998;3(2):131–5.PubMedGoogle Scholar
  31. 31.
    de Jager MW, Gooris GS, Dolbnya IP, Ponec M, Bouwstra JA. Modelling the stratum corneum lipid organisation with synthetic lipid mixtures: the importance of synthetic ceramide composition. Biochim Biophys Acta. 2004;1664(2):132–40.PubMedCrossRefGoogle Scholar
  32. 32.
    Heisig M, Lieckfeldt R, Wittum G, Mazurkevich G, Lee G. Non steady-state descriptions of drug permeation through stratum corneum. I. The biphasic brick-and-mortar model. Pharm Res. 1996;13(3):421–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Roberts MS, Pugh WJ, Hadgraft J, Watkinson AC. Epidermal permeability penetrant structure relationships.1. An analysis of methods of predicting penetration of monofunctional solutes from aqueous solutions. Int J Pharm. 1995;126(1–2):219–33.CrossRefGoogle Scholar
  34. 34.
    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(1–2):23–32.CrossRefGoogle Scholar
  35. 35.
    Leahy DE, Morris JJ, Taylor PJ, Wait AR. Model solvent systems for qsar.3. An lser analysis of the critical quartet—new light on hydrogen-bond strength and directionality. J Chem Soc Perk Trans 2. 1992;4:705–22.Google Scholar
  36. 36.
    Leahy DE, Morris JJ, Taylor PJ, Wait AR. Model solvent systems for qsar.2. Fragment values (F-Values) for the critical quartet. J Chem Soc Perk Trans 2. 1992;4:723–31.Google Scholar
  37. 37.
    Leahy DE, Taylor PJ, Wait AR. Model solvent systems for qsar,1, Propylene-Glycol Dipelargonate (Pgdp)—a new standard solvent for use in partition-coefficient determination. Quant Struct-Act Relat. 1989;8(1):17–31.CrossRefGoogle Scholar
  38. 38.
    Pagliara A, Caron G, Lisa G, Fan W, Gaillard P, Carrupt PA, et al. Solvatochromic analysis of di-n-butyl ether/water partition coefficients as compared to other solvent systems. J Chem Soc, Perkin Trans 1997;2639–43.Google Scholar
  39. 39.
    Dearden JC, Bresnen GM. The measurement of partition-coefficients. Quant Struct-Act Relat. 1988;7(3):133–44.CrossRefGoogle Scholar
  40. 40.
    Avdeef A. pH-metric log P. II: refinement of partition coefficients and ionization constants of multiprotic substances. J Pharm Sci. 1993;82(2):183–90.PubMedCrossRefGoogle Scholar
  41. 41.
    Scherrer RA, Donovan SF. Automated potentiometric titrations in KCl/water-saturated octanol: method for quantifying factors influencing ion-pair partitioning. Anal Chem. 2009;81(7):2768–78.PubMedCrossRefGoogle Scholar
  42. 42.
    Kamlet MJ, Doherty RM, Abraham MH, Marcus Y, Taft RW. Linear solvation energy relationships.46. An improved equation for correlation and prediction of octanol water partition-coefficients of organic nonelectrolytes (Including strong hydrogen-bond donor solutes). J Phys Chem-Us. 1988;92(18):5244–55.CrossRefGoogle Scholar
  43. 43.
    Abraham MH, Chadha HS. Application of a solvation equation to drug transport properties. In: Pliska V, Testa B, van de Waterbeemd H, editors. Lipophilicity in drug action and toxicology. Weinheim: VCH Publishers; 1996. p. 311–37.CrossRefGoogle Scholar
  44. 44.
    El Tayar N, Tsai RS, Testa B, Carrupt PA, Leo A. Partitioning of solutes in different solvent systems: the contribution of hydrogen-bonding capacity and polarity. J Pharm Sci. 1991;80(6):590–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Steyaert G, Lisa G, Gaillard P, Boss G, Reymond F, Girault HH, et al. Intermolecular forces expressed in 1, 2-dichloroethane-water partition coefficients—a solvatochromic analysis. J Chem Soc Faraday Trans. 1997;93(3):401–6.CrossRefGoogle Scholar
  46. 46.
    Testa B, Crivori P, Reist M, Carrupt PA. The influence of lipophilicity on the pharmacokinetic behavior of drugs: concepts and examples. Perspect Drug Discov. 2000;19(1):179–211.CrossRefGoogle Scholar
  47. 47.
    van de Waterbeemd H, Testa B. The parametrization of lipophilicity and other structural properties in drug design. In: Testa B, editor. Advances in drug research, vol. 16. London: Academic; 1987. p. 87–227.Google Scholar
  48. 48.
    Comer J, Tam K. Lipophilicity profiles: theory and measurement. In: Testa B, van de Waterbeemd H, Folkers G, Guy RH, editors. Pharmacokinetic optimization in drug research: biological, physicochemical and computational strategies. Zurich: Wiley-VHCA; 2001. p. 275–304.CrossRefGoogle Scholar
  49. 49.
    Caron G, Gaillard P, Carrupt PA, Testa B. Lipophilicity behavior of model and medicinal compounds containing a sulfide, sulfoxide, or sulfone moiety. Helv Chim Acta. 1997;80(2):449–62.CrossRefGoogle Scholar
  50. 50.
    Kubinyi H. QSAR: Hansch analysis and related approaches. Weinheim: VCH Publisher; 1993.CrossRefGoogle Scholar
  51. 51.
    Rolando B, Lazzarato L, Di Stilo A, Fruttero R, Carrupt PA, Martel S, et al. Physicochemical profile and in vitro permeation behavior of a new class of non-steroidal anti-inflammatory drug candidates. Eur J Pharm Sci. 2010;40(3):217–21.PubMedCrossRefGoogle Scholar
  52. 52.
    Caron G, Steyaert G, Pagliara A, Reymond F, Crivori P, Gaillard P, et al. Structure-lipophilicity relationships of neutral and protonated beta-blockers Part I Intra- and intermolecular effects in isotropic solvent systems. Helv Chim Acta. 1999;82(8):1211–22.CrossRefGoogle Scholar
  53. 53.
    Caron G, Pagliara A, Gaillard P, Carrupt PA, Testa B. Ionization and partitioning profiles of zwitterions: the case of the anti-inflammatory drug azapropazone. Helv Chim Acta. 1996;79(6):1683–95.CrossRefGoogle Scholar
  54. 54.
    Tsai RS, Testa B, El Tayar N, Carrupt PA. Structure lipophilicity relationships of zwitterionic amino-acids. J Chem Soc Perk Trans 2. 1991;11:1797–802.Google Scholar
  55. 55.
    Tam KY, Avdeef A, Tsinman O, Sun N. The permeation of amphoteric drugs through artificial membranes—an in combo absorption model based on paracellular and transmembrane permeability. J Med Chem. 2010;53(1):392–401.PubMedCrossRefGoogle Scholar
  56. 56.
    Pagliara A, Carrupt PA, Caron G, Gaillard P, Testa B. Lipophilicity profiles of ampholytes. Chem Rev. 1997;97(8):3385–400.PubMedCrossRefGoogle Scholar
  57. 57.
    Kakemi K, Arita T, Hori R, Konishi R, Nishimura K. Absorption and exretion of drugs. XXXIV. An aspect of the mechanism of drug absorption from the intestinal tract in rats. Chem Pharm Bull (Tokyo). 1969;17(2):255–61.Google Scholar
  58. 58.
    Houston JB, Upshall DG, Bridges JW. A re-evaluation of the importance of partition coefficients in the gastrointestinal absorption of anutrients. J Pharmacol Exp Ther. 1974;189(1):244–54.PubMedGoogle Scholar
  59. 59.
    Garrigues TM, Perezvarona AT, Climent E, Bermejo MV, Martinvillodre A, Pladelfina JM. Gastric absorption of acidic xenobiotics in the rat—biophysical interpretation of an apparently atypical behavior. Int J Pharm. 1990;64(2–3):127–38.CrossRefGoogle Scholar
  60. 60.
    Murthy KS, Zografi G. Oil-water partitioning of chlorpromazine and other phenothiazine derivatives using dodecane and normal-octanol. J Pharm Sci. 1970;59(9):1281–5.PubMedCrossRefGoogle Scholar
  61. 61.
    Buur A, Trier L, Magnusson C, Artursson P. Permeability of 5-fluorouracil and prodrugs in Caco-2 cell monolayers. Int J Pharm. 1996;129(1–2):223–31.CrossRefGoogle Scholar
  62. 62.
    Komiya I, Park JY, Kamani A, Ho NFH, Higuchi WI. Quantitative mechanistic studies in simultaneous fluid-flow and intestinal-absorption using steroids as model solutes. Int J Pharm. 1980;4(3):249–62.CrossRefGoogle Scholar
  63. 63.
    Taylor DC, Pownall R, Burke W. The absorption of beta-adrenoceptor antagonists in rat in-situ small intestine; the effect of lipophilicity. J Pharm Pharmacol. 1985;37(4):280–3.PubMedCrossRefGoogle Scholar
  64. 64.
    El Tayar N, Tsai RS, Testa B, Carrupt PA, Hansch C, Leo A. Percutaneous penetration of drugs: a quantitative structure-permeability relationship study. J Pharm Sci. 1991;80(8):744–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Singh P, Roberts MS. Skin permeability and local tissue concentrations of nonsteroidal anti-inflammatory drugs after topical application. J Pharmacol Exp Ther. 1984;268:144–51.Google Scholar
  66. 66.
    Schoenwald RD, Huang HS. Corneal penetration behavior of beta-blocking agents I: physiochemical factors. J Pharm Sci. 1983;72(11):1266–72.PubMedCrossRefGoogle Scholar
  67. 67.
    Dearden JC. Molecular structure and drug transport. In: Ramsden CA, Hansch C, Sammer PG, Taylor JB, editors. Comprehensive medicinal chemistry. The rational design, mechanistic study & therapeutic applications of chemical compounds, vol. 4. Oxford: Pergamon; 1990. p. 375–411.Google Scholar
  68. 68.
    Camenisch G, Folkers G, van de Waterbeemd H. Shapes of membrane permeability-lipophilicity curves: extension of theoretical models with an aqueous pore pathway. Eur J Pharm Sci. 1998;6(4):321–9.CrossRefGoogle Scholar
  69. 69.
    Young RC, Mitchell RC, Brown TH, Ganellin CR, Griffiths R, Jones M, et al. Development of a new physicochemical model for brain penetration and its application to the design of centrally acting H2 receptor histamine antagonists. J Med Chem. 1988;31(3):656–71.PubMedCrossRefGoogle Scholar
  70. 70.
    Yoshida F, Topliss JG. Unified model for the corneal permeability of related and diverse compounds with respect to their physicochemical properties. J Pharm Sci. 1996;85(8):819–23.PubMedCrossRefGoogle Scholar
  71. 71.
    von Geldern TW, Hoffman DJ, Kester JA, Nellans HN, Dayton BD, Calzadilla SV, et al. Azole endothelin antagonists. 3. Using delta log P as a tool to improve absorption. J Med Chem. 1996;39(4):982–91.CrossRefGoogle Scholar
  72. 72.
    Plemper van Balen G, Martinet CM, Caron G, Bouchard G, Reist M, Carrupt PA, et al. Liposome/water lipophilicity: methods, information content, and pharmaceutical applications. Med Res Rev. 2004;24(3):299–324.CrossRefGoogle Scholar
  73. 73.
    Seydel JK, Velasco MA, Coats EA, Cordes HP, Kunz B, Wiese M. The importance of drug-membrane interaction in drug research-and-development. Quant Struct-Act Relat. 1992;11(2):205–10.CrossRefGoogle Scholar
  74. 74.
    Malkia A, Murtomaki L, Urtti A, Kontturi K. Drug permeation in biomembranes: in vitro and in silico prediction and influence of physicochemical properties. Eur J Pharm Sci. 2004;23(1):13–47.PubMedCrossRefGoogle Scholar
  75. 75.
    New RRC. Liposomes. A practical approach. Oxford: IRL Press; 1990.Google Scholar
  76. 76.
    Betageri GV, Rogers JA. Thermodynamics of partitioning of beta-blockers in the normal-octanol-buffer and liposome systems. Int J Pharm. 1987;36(2–3):165–73.CrossRefGoogle Scholar
  77. 77.
    Betageri GV, Rogers JA. Correlation of partitioning of nitroimidazoles in the n-octanol/saline and liposome systems with pharmacokinetic parameters and quantitative structure-activity relationships (QSAR). Pharm Res. 1989;6(5):399–403.PubMedCrossRefGoogle Scholar
  78. 78.
    Balon K, Riebesehl BU, Muller BW. Drug liposome partitioning as a tool for the prediction of human passive intestinal absorption. Pharm Res. 1999;16(6):882–8.PubMedCrossRefGoogle Scholar
  79. 79.
    Rogers JA, Choi YW. The liposome partitioning system for correlating biological activities of imidazolidine derivatives. Pharm Res. 1993;10(6):913–7.PubMedCrossRefGoogle Scholar
  80. 80.
    Avdeef A, Box KJ, Comer JE, Hibbert C, Tam KY. pH-metric logP 10. Determination of liposomal membrane-water partition coefficients of ionizable drugs. Pharm Res. 1998;15(2):209–15.PubMedCrossRefGoogle Scholar
  81. 81.
    Pauletti GM, Wunderliallenspach H. Partition-coefficients in-vitro—artificial membranes as a standardized distribution model. Eur J Pharm Sci. 1994;1(5):273–82.CrossRefGoogle Scholar
  82. 82.
    Ong S, Cai SJ, Bernal C, Rhee D, Qiu X, Pidgeon C. Phospholipid immobilization on solid surfaces. Anal Chem. 1994;66(6):782–92.PubMedCrossRefGoogle Scholar
  83. 83.
    Beigi F, Gottschalk I, Hagglund CL, Haneskog L, Brekkan E, Zhang YX, et al. Immobilized liposome and biomembrane partitioning chromatography of drugs for prediction of drug transport. Int J Pharm. 1998;164(1–2):129–37.CrossRefGoogle Scholar
  84. 84.
    Ornskov E, Gottfries J, Erickson M, Folestad S. Experimental modelling of drug membrane permeability by capillary electrophoresis using liposomes, micelles and microemulsions. J Pharm Pharmacol. 2005;57(4):435–42.PubMedCrossRefGoogle Scholar
  85. 85.
    Pidgeon C, Ong S, Liu H, Qiu X, Pidgeon M, Dantzig AH, et al. IAM chromatography: an in vitro screen for predicting drug membrane permeability. J Med Chem. 1995;38(4):590–4.PubMedCrossRefGoogle Scholar
  86. 86.
    Liu H, Ong S, Glunz L, Pidgeon C. Predicting drug-membrane interactions by HPLC: structural requirements of chromatographic surfaces. Anal Chem. 1995;67(19):3550–7.PubMedCrossRefGoogle Scholar
  87. 87.
    Taillardat-Bertschinger A, Carrupt PA, Barbato F, Testa B. Immobilized artificial membrane HPLC in drug research. J Med Chem. 2003;46(5):655–65.PubMedCrossRefGoogle Scholar
  88. 88.
    Marcus Y, Migron Y. Polarity, hydrogen-bonding, and structure of mixtures of water and cyanomethane. J Phys Chem-Us. 1991;95(1):400–6.CrossRefGoogle Scholar
  89. 89.
    Hanna M, de Biasi V, Bond B, Camilleri P, Hutt A. Biomembrane lipids as components of chromatographic phases: comparative chromatography on coated and bonded phases. Chromatographia. 2000;52:710–20.CrossRefGoogle Scholar
  90. 90.
    Barbato F, di Martino G, Grumetto L, La Rotonda MI. Can protonated beta-blockers interact with biomembranes stronger than neutral isolipophilic compounds? A chromatographic study on three different phospholipid stationary phases (IAM-HPLC). Eur J Pharm Sci. 2005;25(4–5):379–86.PubMedCrossRefGoogle Scholar
  91. 91.
    Barbato F, La Rotonda MI, Quaglia F. Interactions of nonsteroidal antiinflammatory drugs with phospholipids: comparison between octanol/buffer partition coefficients and chromatographic indexes on immobilized artificial membranes. J Pharm Sci. 1997;86(2):225–9.PubMedCrossRefGoogle Scholar
  92. 92.
    Barbato F, La Rotonda MI, Quaglia F. Chromatographic indices determined on an immobilized artificial membrane (IAM) column as descriptors of lipophilic and polar interactions of 4-phenyldihydropyridine calcium-channel blockers with biomembranes. Eur J Med Chem. 1996;31(4):311–8.CrossRefGoogle Scholar
  93. 93.
    Liu X, Hefesha H, Scriba G, Fahr A. Retention behavior of neutral, positively and negatively charged solutes on immobilized artificial membrane (IAM) stationary. Helv Chim Acta. 2008;91:1505–12.CrossRefGoogle Scholar
  94. 94.
    Taillardat-Bertschinger A, Martinet CA, Carrupt PA, Reist M, Caron G, Fruttero R, et al. Molecular factors influencing retention on immobilized artifical membranes (IAM) compared to partitioning in liposomes and n-octanol. Pharm Res. 2002;19(6):729–37.PubMedCrossRefGoogle Scholar
  95. 95.
    Ong S, Liu H, Pidgeon C. Immobilized-artificial-membrane chromatography: measurements of membrane partition coefficient and predicting drug membrane permeability. J Chromatogr A. 1996;728(1–2):113–28.PubMedCrossRefGoogle Scholar
  96. 96.
    Nasal A, Sznitowska M, Bucinski A, Kaliszan R. Hydrophobicity parameter from high-performance liquid-chromatography on an immobilized artificial membrane column and its relationship to bioactivity. J Chromatogr A. 1995;692(1–2):83–9.CrossRefGoogle Scholar
  97. 97.
    Genty M, Gonzalez G, Clere C, Desangle-Gouty V, Legendre JY. Determination of the passive absorption through the rat intestine using chromatographic indices and molar volume. Eur J Pharm Sci. 2001;12(3):223–9.PubMedCrossRefGoogle Scholar
  98. 98.
    Pehourcq F, Matoga M, Bannwarth B. Diffusion of arylpropionate non-steroidal anti-inflammatory drugs into the cerebrospinal fluid: a quantitative structure-activity relationship approach. Fundam Clin Pharmacol. 2004;18(1):65–70.PubMedCrossRefGoogle Scholar
  99. 99.
    Lazaro E, Rafols C, Abraham MH, Roses M. Chromatographic estimation of drug disposition properties by means of immobilized artificial membranes (IAM) and C18 columns. J Med Chem. 2006;49(16):4861–70.PubMedCrossRefGoogle Scholar
  100. 100.
    Kotecha J, Shah S, Rathod I, Subbaiah G. Prediction of oral absorption in humans by experimental immobilized artificial membrane chromatography indices and physicochemical descriptors. Int J Pharm. 2008;360(1–2):96–106.PubMedCrossRefGoogle Scholar
  101. 101.
    Shin BS, Yoon CH, Balthasar JP, Choi BY, Hong SH, Kim HJ, et al. Prediction of drug bioavailability in humans using immobilized artificial membrane phosphatidylcholine column chromatography and in vitro hepatic metabolic clearance. Biomed Chromatogr. 2009;23(7):764–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Boija E, Johansson G. Interactions between model membranes and lignin-related compounds studied by immobilized liposome chromatography. Biochim Biophys Acta. 2006;1758(5):620–6.PubMedCrossRefGoogle Scholar
  103. 103.
    Beigi F, Yang Q, Lundahl P. Immobilized-liposome chromatographic analysis of drug partitioning into lipid bilayers. J Chromatogr A. 1995;704(2):315–21.PubMedCrossRefGoogle Scholar
  104. 104.
    Osterberg T, Svensson M, Lundahl P. Chromatographic retention of drug molecules on immobilised liposomes prepared from egg phospholipids and from chemically pure phospholipids. Eur J Pharm Sci. 2001;12(4):427–39.PubMedCrossRefGoogle Scholar
  105. 105.
    Wiedmer SK, Jussila MS, Riekkola ML. Phospholipids and liposomes in liquid chromatographic and capillary electromigration techniques. TrAC Trends Anal Chem. 2004;23(8):562–82.CrossRefGoogle Scholar
  106. 106.
    Yang Q, Liu XY, Ajiki S, Hara M, Lundahl P, Miyake J. Avidin-biotin immobilization of unilamellar liposomes in gel beads for chromatographic analysis of drug-membrane partitioning. J Chromatogr B Biomed Sci Appl. 1998;707(1–2):131–41.PubMedCrossRefGoogle Scholar
  107. 107.
    Liu XY, Nakamura C, Yang Q, Kamo N, Miyake J. Immobilized liposome chromatography to study drug-membrane interactions. Correlation with drug absorption in humans. J Chromatogr A. 2002;961(1):113–8.PubMedCrossRefGoogle Scholar
  108. 108.
    Liu X, Fan P, Chen M, Scriba G, Gabel D, Fahr A. Drug-membrane interaction on immobilized liposome chromatography compared to immobilized artificial membrane (IAM), liposome/water and n-octanol/water systems. Helv Chim Acta. 2010;93:203–11.CrossRefGoogle Scholar
  109. 109.
    Burns ST, Khaledi MG. Rapid determination of liposome-water partition coefficients (Klw) using liposome electrokinetic chromatography (LEKC). J Pharm Sci. 2002;91(7):1601–12.PubMedCrossRefGoogle Scholar
  110. 110.
    Zhang Y, Zhang R, Hjerten S, Lundahl P. Liposome capillary electrophoresis for analysis of interactions between lipid bilayers and solutes. Electrophoresis. 1995;16(8):1519–23.PubMedCrossRefGoogle Scholar
  111. 111.
    Wiedmer SK, Shimmo R. Liposomes in capillary electromigration techniques. Electrophoresis. 2009;30:S240–57.PubMedCrossRefGoogle Scholar
  112. 112.
    Muhonen J, Holopainen JM, Wiedmer SK. Interactions between local anesthetics and lipid dispersions studied with liposome electrokinetic capillary chromatography. J Chromatogr A. 2009;1216(15):3392–7.PubMedCrossRefGoogle Scholar
  113. 113.
    Helle A, Makitalo J, Huhtanen J, Holopainen JM, Wiedmer SK. Antibiotic fusidic acid has strong interactions with negatively charged lipid membranes: an electrokinetic capillary chromatographic study. Biochim Biophys Acta. 2008;1778(11):2640–7.PubMedCrossRefGoogle Scholar
  114. 114.
    Carrozzino JM, Khaledi MG. Interaction of basic drugs with lipid bilayers using liposome electrokinetic chromatography. Pharm Res. 2004;21(12):2327–35.PubMedCrossRefGoogle Scholar
  115. 115.
    Wiedmer SK, Holopainen JM, Mustakangas P, Kinnunen PK, Riekkola ML. Liposomes as carriers in electrokinetic capillary chromatography. Electrophoresis. 2000;21(15):3191–8.PubMedCrossRefGoogle Scholar
  116. 116.
    Wang YJ, Sun J, Liu HZ, Wang YJ, He ZG. Prediction of human drug absorption using liposome electrokinetic chromatography. Chromatographia. 2007;65(3–4):173–7.CrossRefGoogle Scholar
  117. 117.
    Wang YJ, Sun J, Liu HZ, He ZG. Rapidly profiling blood-brain barrier penetration with liposome EKC. Electrophoresis. 2007;28(14):2391–5.PubMedCrossRefGoogle Scholar
  118. 118.
    Wang YJ, Sun J, Liu HZ, Liu JF, Zhang LQ, Liu K, et al. Predicting skin permeability using liposome electrokinetic chromatography. Analyst. 2009;134(2):267–72.PubMedCrossRefGoogle Scholar
  119. 119.
    Ermondi G, Caron G. Recognition forces in ligand-protein complexes: blending information from different sources. Biochem Pharmacol. 2006;72(12):1633–45.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Pharmaceutical TechnologyFriedrich-Schiller-Universität JenaJenaGermany
  2. 2.Pharmacy DepartmentUniversity Hospital Centre, CHUV-BH04LausanneSwitzerland

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