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Quantifying In Vivo Luminal Drug Solubilization -Supersaturation-Precipitation Profiles to Explain the Performance of Lipid Based Formulations

Authors
  • Tanaka, Yusuke1, 2
  • Tay, Erin1
  • Nguyen, Tri-Hung1
  • Porter, Christopher J. H.1, 3
  • 1 Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia , Parkville (Australia)
  • 2 Hiroshima International University, 5-1-1 Hiro-koshingai, Kure, Hiroshima, 737-0112, Japan , Hiroshima (Japan)
  • 3 Monash University, Parkville, Victoria, 3052, Australia , Parkville (Australia)
Type
Published Article
Journal
Pharmaceutical Research
Publisher
Springer-Verlag
Publication Date
Feb 03, 2020
Volume
37
Issue
3
Identifiers
DOI: 10.1007/s11095-020-2762-9
Source
Springer Nature
Keywords
License
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Abstract

PurposeTo evaluate the role of supersaturation in the in vivo absorption of fenofibrate (FFB), after oral administration in a medium-chain lipid-based formulation (MCLBF).MethodsFFB was loaded at 90% and 20% w/w of saturated solubility in MCLBF. The two formulations were pre-dispersed in purified water at 5% w/w (ME90% and 20%, respectively) and orally administered to rats to measure in vivo luminal drug concentrations.ResultsFFB precipitated in the stomach due to lipid digestion by gastric lipases and loss of solubilization capacity. This was most significant for ME90%. For ME90%, a high degree of supersaturation was also observed in the duodenum, however, precipitated FFB crystals rapidly re-dissolved. The combination of supersaturation and rapid re-dissolution appeared to drive effective absorption in the upper intestine. For ME20%, FFB precipitated in the stomach but not in the crystalline form and rapidly re-dissolved. Supersaturation in the duodenum again appeared to be the major driver of oral absorption.ConclusionsThe data provide one of the first studies of in vivo luminal drug concentration, supersaturation and absorption from lipid based formulations and suggests that for FFB, whilst very high supersaturation may drive in vitro and in vivo precipitation, re-dissolution and drug absorption is rapid and efficient.

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