permeability

Permeability measures how readily a drug slips across a biological barrier — most often the wall of the intestine. If dissolution decides how much drug is dissolved and waiting at the membrane, permeability decides how fast that dissolved drug can get through. Think of a crowd at a turnstile: even with plenty of people ready (dissolved drug), a slow turnstile (low permeability) limits how many pass per minute.

Quantitatively, permeability is expressed as an effective permeability coefficient (Peff, in cm/s), the proportionality between flux across the membrane and the concentration gradient driving it (Fick's first law). It depends on the drug's lipophilicity (log P), degree of ionization at the gut pH, molecular size, and whether transporters help or hinder. Lipophilic, small, un-ionized molecules generally permeate well.

In the BCS, a drug is 'highly permeable' when at least about 85–90% of an oral dose is absorbed, judged from human mass-balance or absolute bioavailability studies, or from validated permeability models such as Caco-2 cell monolayers or PAMPA assays. A real caveat: efflux transporters like P-glycoprotein can pump drug back into the gut, so measured permeability is a net result, not just passive crossing.