Virtual intestine

Beskrivning

The overall aim of this work is to develop MD simulation protocols applicable to complex and lipid-rich water-based systems, which we then will use to explore drug solubilization in fasted and fed state intestinal fluids. The hypothesis is that this approach results in unique insights of interactions at the molecular level that will help us understand drug dissolution, solubilization and precipitation in vivo. In addition, future applications will include computational design of advanced drug delivery systems since the extent to which a particular LBF will maintain supersaturation will be possible to explore taking use of the MD simulation protocols established.

In the work with the virtual intestine we computationally produce intestinal fluids that mimick data obtained after in vivo aspiration of healthy volunteers in the fasted and fed state (data obtained in collaboration with University of Leuven). The intestinal fluids are composed of complex, multicomponent systems of phospholipids, bile salts, excipients and food components, all being a physiological concentration in our simulations.

To allow large enough systems as well as detailed molecular interactions to be explored we make use of different resolution scales (all atom, united atoms, coarse grained). When established the virtual intestine will be used to explore performance (dilution, digestion, absorption) of lipid-based formulations, supersaturation tendency of amorphous and carrier based dosage forms as well as specific interactions between excipients, drugs and naturally available colloidal structures of the intestinal fluid. The drug delivery systems can then be simulated in the same way as airplanes are simulated before first time in the air; the dosage form is tested extensively in the virtual intestine for its performance (dissolution, solubility and absorption-wise) and is therefore optimized for these properties prior to first time in man.