title: Biopharmaceutical modeling of drug supersaturation during lipid-based formulation digestion considering an absorption sink.
abstract: OBJECTIVE
  In vitro lipolysis is widely utilized for predicting in vivo performance of oral lipid-based formulations (LBFs). However, evaluation of LBFs in the absence of an absorption sink may have limited in vivo relevance. This study aimed at employing biopharmaceutical modeling to simulate LBF digestion and drug supersaturation in a continuous absorptive environment.
  
  
  METHODS
  Three fenofibrate-loaded LBFs were characterized in vitro (dispersion and lipolysis) and drug precipitation was monitored using in-line Raman spectroscopy. In vitro data were combined with pharmacokinetic data derived from an in vivo study in pigs to simulate intestinal LBF transit. This biopharmaceutical model allowed calculation of lipolysis-triggered drug supersaturation while drug and lipolysis products are absorbed from the intestine.
  
  
  RESULTS
  The biopharmaceutical model predicted that, in a continuous absorption environment, fenofibrate supersaturation was considerably lower compared to in vitro lipolysis (non-sink). Hence, the extensive drug precipitation observed in vitro was predicted to be unlikely in vivo. The absorption of lipolysis products increased drug supersaturation, but drug precipitation was unlikely for highly permeable drugs.
  
  
  CONCLUSIONS
  Biopharmaceutical modeling is a valuable approach for predicting LBFs performance in vivo. In the absence of in vitro tools simulating absorptive conditions, modeling strategies should be further considered.
authors: Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056, Basel, Switzerland.
authors: Cordula
authors: C
authors: Stillhart
authors: Georgios
authors: G
authors: Imanidis
authors: Brendan T
authors: BT
authors: Griffin
authors: Martin
authors: M
authors: Kuentz
mesh_terms: D000818:Animals; D001682:Biological Availability; D001702:Biopharmaceutics; D002626:Chemistry, Pharmaceutical; D011345:Fenofibrate / Q000008:administration & dosage / Q000493:pharmacokinetics; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008055:Lipids / Q000737:chemistry*; D008066:Lipolysis; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013059:Spectrum Analysis, Raman; D013552:Swine; D014961:X-Ray Diffraction
chemical_list: D000960:Hypolipidemic Agents; D008055:Lipids; D004364:Pharmaceutical Preparations; D011345:Fenofibrate