permeability

Permeability is a molecule's ability to slip across the fatty walls that wrap every cell. Those membranes act like an oily curtain: a molecule that wants to enter the bloodstream from the gut, or reach a target inside a cell, must pass through this barrier rather than around it.

Passive permeability favors molecules that are reasonably greasy, not too large, and not heavily charged, with few hydrogen-bond donors. Each polar group it carries must shed its shell of water to enter the membrane, which costs energy, so very polar molecules permeate poorly. This is why polar surface area and hydrogen-bond donor count are watched so closely.

Permeability is not the whole story of absorption. Some molecules are actively pumped in by transporters or, conversely, pumped back out by efflux proteins, and some cross between cells rather than through them. Common ways to measure it include the Caco-2 cell assay and the artificial-membrane PAMPA assay.