TY - JOUR
T1 - Pancreatic lipase digestion
T2 - The forgotten barrier in oral administration of lipid-based delivery systems?
AU - Zupančič, Ožbej
AU - Kushwah, Varun
AU - Paudel, Amrit
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/10
Y1 - 2023/10
N2 - This review highlights the importance of controlling the digestion process of orally administered lipid-based delivery systems (LBDS) and their performance. Oral LBDS 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 rate. 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 LBDS with ester-free excipients. Recent in vivo studies demonstrated that digestion inhibition lead to altered pharmacokinetic profiles, where Cmax and Tmax were reduced in spite of same AUC compared to control or even improved oral bioavailability.
AB - This review highlights the importance of controlling the digestion process of orally administered lipid-based delivery systems (LBDS) and their performance. Oral LBDS 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 rate. 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 LBDS with ester-free excipients. Recent in vivo studies demonstrated that digestion inhibition lead to altered pharmacokinetic profiles, where Cmax and Tmax were reduced in spite of same AUC compared to control or even improved oral bioavailability.
KW - Lipase inhibition
KW - Lipid digestion
KW - Lipid-based delivery systems
KW - Pancreatic lipase
KW - pH stat model
UR - http://www.scopus.com/inward/record.url?scp=85169834736&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2023.08.024
DO - 10.1016/j.jconrel.2023.08.024
M3 - Review article
C2 - 37579977
AN - SCOPUS:85169834736
SN - 0168-3659
VL - 362
SP - 381
EP - 395
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -