SolubilityDiffusionModell

The Solubility-Diffusion Modell, also known as the solution-diffusion model, describes the passive transport of small, typically neutral molecules across biological membranes. In this framework a penetrant first dissolves in the lipid membrane, diffuses through the hydrophobic core, and partitions back into the aqueous phases on either side of the membrane. The overall permeability P is approximated by P = (D_m × K) / l, where D_m is the diffusion coefficient within the membrane, K is the partition coefficient between membrane and water, and l is the membrane thickness. Under steady-state conditions the flux J across the membrane is J = P × ΔC, with ΔC the concentration difference across the membrane.

The model highlights how molecular properties influence permeability. D_m reflects size and interaction with the lipid interior, while K increases with lipophilicity, making more lipophilic compounds generally more permeable up to a point. The framework provides a simple, quantitative link between chemical structure and membrane transport, and is widely used in pharmacokinetics and membrane biophysics to interpret and predict the permeability of neutral and weakly polar compounds. It supports screening of drug candidates for intestinal absorption and for crossing barriers such as the blood-brain barrier, often in conjunction with in vitro assays.

Limitations include its inapplicability to charged or highly polar molecules, which often require alternative transport mechanisms. It does not account for active transport, carrier-mediated uptake, pores, or membrane heterogeneity and protein interactions. Despite simplifications, the model remains a foundational tool for understanding and estimating membrane permeability based on solubility and diffusion in the lipid phase.