Zupancic_2023_J.Control.Release__

This review highlights the importance of controlling the digestion process of orally administered lipid-based delivery systems (LBDS) and their performance. Oral LBDS delivery are prone to digestion via pancreatic lipase in the small intestine. Rapid or uncontrolled digestion may cause the loss of delivery system integrity, its structural changes, reduced solubilization capacity and physical stability issues. All these events can lead to uncontrolled drug release from the digested LBDS into the gastrointestinal environment, exposing the incorporated drug to precipitation or degradation by luminal proteases. To prevent this, the digestion rate of orally administered LBDS can be estimated by appropriate choice of the formulation type, excipient combinations and their ratios. In addition, in vitro digestion models like pH-stat are useful tools to evaluate the formulation digestion performance. Controlling digestion can be achieved by conventional lipase inhibitors like orlistat, sterically hindering of lipase adsorption on the delivery system surface with polyethylene glycol (PEG) chains, lipase desorption or saturation of the interface with surfactants as well as formulating with ester-free excipients. Recent in vivo studies demonstrated that digestion inhibition lead to altered pharmacokinetic profiles, where C(max) and T(max) were reduced in spite of same AUC compared to control or even improved oral bioavailability.