Membrane Permeability Calculators

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Membrane permeability describes how easily a substance crosses a biological lipid bilayer membrane. The lipid bilayer is selectively permeable — small, nonpolar molecules cross freely while ions and large polar molecules are blocked. Permeability (P) is determined by the membrane-water partition coefficient (K) and the diffusion coefficient (D) within the bilayer, divided by membrane thickness (d): P = K × D / d. Membrane permeability determines drug bioavailability, toxin penetration, and cellular homeostasis, and is a critical parameter in early-stage drug development.

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Permeability Coefficient Formula

P = K × D / d

K = lipid-water partition coefficient; D = diffusion coefficient within the membrane; d = membrane thickness (~7–10 nm). Flux across the membrane: J = P × ΔC, where ΔC is concentration difference across the membrane.

Permeability of Different Molecule Classes

  • High P (>10⁻⁶ cm/s): O₂, CO₂, ethanol, steroid hormones, small lipophilic drugs
  • Moderate (∼10⁻⁸ cm/s): Water (through bilayer), urea, glycerol
  • Low (less than 10⁻¹⁰ cm/s): Na⁺, K⁺, Cl⁻, glucose, amino acids, ATP

Lipinski's Rule of Five

Predicts good membrane permeability (oral bioavailability) when: MW ≤ 500 Da; logP ≤ 5; H-bond donors ≤ 5; H-bond acceptors ≤ 10. These rules identify drug candidates likely to cross gut epithelium by passive diffusion and are a standard filter in pharmaceutical lead optimization.

Measurement Methods

Membrane permeability is measured using: PAMPA (Parallel Artificial Membrane Permeability Assay) for passive diffusion prediction; Caco-2 cell monolayers for intestinal permeability; patch clamp for single-channel ion permeability in living cells. Caco-2 Papp >10⁻⁶ cm/s predicts high oral absorption; Papp <10⁻⁷ cm/s predicts poor absorption.

Glossary

Permeability Coefficient (P)
A measure of membrane crossing ease: P = K × D / d (units: cm/s); determines flux for a given concentration gradient across a membrane.
Partition Coefficient (K / logP)
The ratio of compound concentration in lipid vs. aqueous phase; high logP means lipophilic and high membrane permeability; logP ≤ 5 is a key Lipinski oral bioavailability criterion.
Lipinski's Rule of Five
Guidelines predicting good oral drug absorption: MW ≤ 500 Da, logP ≤ 5, H-bond donors ≤ 5, H-bond acceptors ≤ 10; violations predict poor membrane permeability or solubility.

Frequently Asked Questions

Passive membrane permeability is governed by P = K × D / d, where K is the lipid-water partition coefficient (lipophilicity), D is the diffusion coefficient in the membrane, and d is thickness. High logP (lipophilic) molecules have high K and cross freely. Charged ions have effectively zero passive permeability (K ≈ 10⁻¹⁴ for Na⁺) and require ion channels or pumps. Molecular size also matters — larger molecules have lower D and cross more slowly.

Ions (Na⁺, K⁺, Cl⁻) carry charge and are surrounded by a hydration shell of water molecules. Crossing the hydrophobic bilayer core would require stripping this hydration shell — an energetically very unfavorable process (~150–200 kJ/mol). The resulting lipid-water partition coefficient for ions is essentially zero, making passive permeability negligible. Ion channels overcome this by providing a hydrophilic pore allowing ions to cross without contacting the hydrophobic core.

Lipinski's Rule of Five predicts that a drug will have good oral absorption (can cross intestinal membranes by passive diffusion) if: molecular weight ≤ 500 Da, logP ≤ 5 (not too lipophilic), hydrogen bond donors ≤ 5, hydrogen bond acceptors ≤ 10. Violating two or more rules usually predicts poor oral bioavailability. These rules are used in pharmaceutical early screening to filter compounds before expensive in vivo testing.

Caco-2 cells are human intestinal epithelial cells that form tight junctions and express transporters similar to the small intestine. The assay measures how fast a drug crosses this monolayer from apical (intestinal lumen side) to basolateral (blood side). Apparent permeability Papp > 10⁻⁶ cm/s predicts high intestinal absorption; Papp < 10⁻⁷ predicts poor absorption. It is a standard early pharmaceutical screening assay used before in vivo studies.