In medicinal chemistry, Drug Permeability is an empirical parameter that indicates the likelihood of a chemical entity or an active pharmaceutical ingredient to cross biological barrier and to became bioavailable in the body. Drug permeability, together with drug aqueous solubility are the two parameters which defines the fate of the active ingredient after oral administration that ultimately defines its bioavailability.^[1] When drug permeability is empirically measured in vitro, it is generally called apparent permeability (P_app) as its absolute value varies according to the method selected for its measurement. P_app is measured in vitro utilizing cellular based barriers such as the Caco-2^[2] model or utilizing artificial biomimetic barriers, such as the Parallel Artificial Membrane Permeation Assay (PAMPA)^[3] or the PermeaPad.^[4] All these methods are built on an acceptor compartment (from 0.2 up to several mL according to the method uses) where the drug solution is placed, a biomimetic barrier and an acceptor compartment, where the drug concentration is quantified over time. By maintaining sink condition, a steady state is reached after a lag time (τ, Fig. 1) .

Data Analysis

Figure 1. Drug flux diagram

The drug flux represents the slope of the linear regression of the accumulated mass (Q) over time (t) normalized over the permeation area (A), i.e., the surface area of the barrier available for permeation.

Equation 1: ${\displaystyle j=dQ/dt*1/A}$

The drug apparent permeability (P_app) is calculated by normalizing the drug flux (j) over the initial concentration of the API in the donor compartment (c₀) as:

Equation 2: ${\displaystyle P_{app}=j/c_{0}}$

Dimensionally, the P_app represents a velocity, and it is normally expressed in cm/sec. The highest is the permeability, the highest is expected to be the bioavailability of the drug after oral administration.

References