The AAPS Journal

, Volume 16, Issue 3, pp 539–549 | Cite as

In Vitro Lipolysis Data Does Not Adequately Predict the In Vivo Performance of Lipid-Based Drug Delivery Systems Containing Fenofibrate

  • Nicky Thomas
  • Katharina Richter
  • Thomas B. Pedersen
  • René Holm
  • Anette Müllertz
  • Thomas Rades
Research Article

Abstract

The present study investigated the utility of in vitro lipolysis performance indicators drug solubilization and maximum supersaturation ratio (SRM) for their predictive use for the in vivo performance in a minipig model. The commercial Lipanthyl formulation and a series of LbDDS based on identical self-nanoemulsifying drug delivery systems (SNEDDS) containing 200 mg of fenofibrate, either dissolved or suspended, were subjected to combined gastric (pH 2) and intestinal (pH 6.5) in vitro lipolysis. Based on the solubilization profiles and SRM the rank-order SNEDDS (75% drug load) > super-SNEDDS (150% drug load, dissolved) = SNEDDS suspension (150% drug load, partially suspended) > Lipanthyl was established, with an increased likelihood of drug precipitation above SRM > 3. The in vitro performance, however, was not reproduced in vivo in a minipig model as the mean plasma concentration over time curves of all LbDDS were comparable, independent of the initial physical state of the drug. There was no correlation between the area under the solubilization-time curves (AUCin vitro) of the intestinal step and the AUCin vivo. The study suggests careful interpretation of in vitro performance criteria and revision of LbDDS optimization towards increased solubilization.

KEY WORDS

in vitro ipolysis in vitro/in vivo correlation lipids SNEDDS suspensions super-SNEDDS supersaturation 

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Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  • Nicky Thomas
    • 1
    • 2
  • Katharina Richter
    • 1
    • 2
  • Thomas B. Pedersen
    • 1
  • René Holm
    • 3
  • Anette Müllertz
    • 1
    • 4
  • Thomas Rades
    • 1
  1. 1.Department of Pharmacy, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
  2. 2.Ian Wark Research InstituteUniversity of South AustraliaMawson LakesAustralia
  3. 3.Biologics and Pharmaceutical ScienceValbyDenmark
  4. 4.Bioneer:FARMA, Danish Drug Development Center, Department of Pharmacy, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark

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