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Pharmaceutical Research

, Volume 21, Issue 8, pp 1405–1412 | Cite as

Susceptibility to Lipase-Mediated Digestion Reduces the Oral Bioavailability of Danazol After Administration as a Medium-Chain Lipid-Based Microemulsion Formulation

  • Christopher J. H. Porter
  • Ann Marie Kaukonen
  • Ben J. Boyd
  • Glenn A. Edwards
  • William N. Charman
Article

Abstract

Purpose. To investigate the impact of lipidic formulation type on in vitro dispersion and digestion properties and the relationship to oral bioavailability, using danazol as a model lipophilic poorly water-soluble drug.

Methods. Three lipid-based danazol formulations [a long-chain triglyceride solution (LCT-solution) and self-microemulsifying drug delivery systems (SMEDDS) based on long-chain (C18) lipids (LC-SMEDDS) and medium-chain (C8-C10) lipids (MC-SMEDDS)] were adminis- tered to fasted beagle dogs and compared with a micronized danazol formulation administered postprandially and in the fasted state. In vitro dispersion and particle size data for the two SMEDDS were compared, and the distribution/solubilization patterns of danazol across the various phases produced during in vitro digestion quantified.

Results. The LCT-solution and LC-SMEDDS formulations significantly enhanced the oral bioavailability of danazol when compared to fasted administration of the powder formulation. In contrast, and despite displaying excellent dispersion properties, the MC-SMEDDS resulted in little enhancement in danazol bioavailability. In support of the in vivo findings, in vitro digestion of the medium-chain formulation resulted in significant drug precipitation when compared with the long-chain lipid formulations.

Conclusions. Digestion of microemulsion preconcentrate formulations based on medium-chain lipids may limit in vivo utility when compared with similar formulations based on long chain lipids.

absorption bioavailability dispersion lipid-based drug delivery lipid digestion poorly water-soluble drugs 

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Copyright information

© Plenum Publishing Corporation 2004

Authors and Affiliations

  • Christopher J. H. Porter
    • 1
  • Ann Marie Kaukonen
    • 1
    • 2
  • Ben J. Boyd
    • 1
  • Glenn A. Edwards
    • 3
  • William N. Charman
    • 1
  1. 1.Department of Pharmaceutics, Victorian College of PharmacyMonash University (Parkville Campus)ParkvilleAustralia. (e-mail: Chris.Porter@vcp.monash.edu.au)
  2. 2.Viikki Drug Discovery Technology Center, Division of Pharmaceutical Technology, Faculty of PharmacyUniversity of HelsinkiFinland
  3. 3.Department of Veterinary SciencesThe University of MelbourneWerribeeAustralia

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