Predicting Drug Membrane Permeability

Fluid Membrane Bilayer can be modeled by IAM column. Immobilized Artificial Membrane (IAM) chromatography has recently gained acceptance amoung drug discovery chemists for estimating the membrane of small molecule drugs. The figure below illustrates that the interaction between membrane bilayer and drug can be modeled by the IAM column/drug system. KIAM, the equilibrium constant describing the relative concentrations of drug in the membrane and in the external fluid, is analogous to the k' IAM. Fluid membrane bilayer can be modeled by IAM column.

This IAM technique provides superior correlation with experimentally determined drug permeability when compared to other chromatographic methods. IAM more closely mimics the interaction of analytes with biological membranes, where a combination of hydrophobic, ion pairing, and hydrogen bonding interactions are possible. The combination of interactions measured by the IAM column is known as phospholipophilicity.

These advantages have led to the development of several new IAM phases used by predicting membrane permeability.

The IAM.PC.DD2 packing offers the following advantages:

  • More Hydrophobic: The IAM.PC.DD2 offers more hydrophobicity, thus giving longer retentions to compounds not well retained on the IAM.PC.DD packing. Retentions are typically double on the IAM.PC.DD2 column than on the DD column and exhibit excellent correlation for groups of compounds.
  • Greater Stability: Another distinct advantage of the IAM.PC.DD2 packing is its ability to tolerate mobile phases between pH's 7.0 and 7.5, thus resulting in longer column life under these conditions.
  • Excellent Correlation to Traditional Methods: The traditional means of predicting membrane permeability include the use of Caco-2 cell line cultures, intestinal tissue, or liposom assays. These methods are laborious and costly to perform.
  • Intestinal Tissue Correlation: Measuring drug permeability in the intestinal tissue, where absorption is occuring, is physiologically more relevant than measuring drug permeability in Caco-2 cells.
Correlating Drug Partitioning into IAM with Rat Intestinal Drug Absorption
Sample % Absorption of Inverted Rat Intestine (k') IAM.PC.DD (k') IAM.PC.DD2
m-nitroaniline 77 3.875 10.838
p-nitroanaline 68 8.576 16.086
salicylic acid 60 1.936 6.963
p-toluidine 59 1.554 4.546
aniline 54 0.811 2.069
m-nitrobenzoic acid 53 1.213 4.403
phenol 51 2.965 6.544
benzoic acid 51 0.531 2.088
acetanilide 32 0.685 3.350
antipyrine 32 0.685 3.350
theophyline 29 0.583 1.478
acetysalcylic acid 20 0.197 0.931
r (correlation factor)   0.8088
0.8025


The interaction between membrane bilayer and drug can be modeled by the IAM column/drug system.           The traditional means of predicting membrane permeability include the use of Caco-2 cell line cultures, intestinal tissue, or liposom assays. These methods are laborious and costly to perform.


Email the Chromatography Department (chromsales@registech.com) for more information on how IAM Drug Discovery Columns can help with your project.

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