Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs.
Highly potent, but poorly water-soluble, drug candidates are common outcomes of contemporary drug discovery programmes and present a number of challenges to drug development - most notably, the issue of reduced systemic exposure after oral administration. However, it is increasingly apparent that formulations containing natural and/or synthetic lipids present a viable means for enhancing the oral bioavailability of some poorly water-soluble, highly lipophilic drugs. This Review details the mechanisms by which lipids and lipidic excipients affect the oral absorption of lipophilic drugs and provides a perspective on the possible future applications of lipid-based delivery systems. Particular emphasis has been placed on the capacity of lipids to enhance drug solubilization in the intestinal milieu, recruit intestinal lymphatic drug transport (and thereby reduce first-pass drug metabolism) and alter enterocyte-based drug transport and disposition.
Porter
Christopher J H
CJ
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, Parkville campus, 381 Royal Parade, Parkville, Victoria 3052, Australia. chris.porter@vcp.monash.edu.au
Trevaskis
Natalie L
NL
Charman
William N
WN
D000284:Administration, Oral; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007408:Intestinal Absorption; D008055:Lipids / Q000737:chemistry* / Q000493:pharmacokinetics; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism
D005079:Excipients; D008055:Lipids; D004364:Pharmaceutical Preparations