The absorption of drugs and other substances from the small intestine is impacted by dose size, concentration, coadministration with food, hydration, the substances physicochemical characteristics, the concentration of endogenous agents such as digestive enzymes and bile acids, longitudinal distribution and the transit time. Modelling the contribution of factors influencing drug absorption, independently of metabolism and clearance, is reliant on dissolution experiments or results derived from animal dosing experiments.
We are interested in alternative oral dosing formats, including for veterinary applications, and understanding the influence of how important the longitudinal distribution of formulations is to absorption efficiency, particularly for lipophilic drugs.
To facilitate such studies, we have constructed a multi-chambered dynamic dissolution apparatus in which the dose form can be mixed with simulated or scavenged gastrointestinal fluids, digesta, buffered media or other relevant aqueous samples in a chamber that is separated from a simulated blood volume by a semipermeable membrane. The design allows the simulation of peristaltic mixing, either in aqueous media or in the presence of diffusion limiting or sorbing effects of digesta (eg cellulose bulk).
Multiple longitudinally separated sampling and addition ports allow the impact of drug absorption or transit to be modelled. Data will be presented for representative agents from BCS classes 1 to 4 that illustrates the increasing importance of longitudinal distribution and surface area on drug absorption for substances with low solubility (BCS 2 and 4) and low permeability (BCS 3 and 4).