Pharmaceutical Research

, Volume 20, Issue 7, pp 1093–1100 | Cite as

Improving Relative Bioavailability of Dicumarol by Reducing Particle Size and Adding the Adhesive Poly(Fumaric-Co-Sebacic) Anhydride

  • C. G. Thanos
  • Z. Liu
  • J. Reineke
  • E. Edwards
  • E. Mathiowitz
Article

Abstract

Purpose. This study was carried out to show the effect of particle size reduction and bioadhesion on the dissolution and relative bioavailability of dicumarol.

Methods. Formulations were produced by a variety of methods including a novel technique to reduce particle size as well as phase inversion with poly(fumaric-co-sebacic)anhydride p(FA:SA) to create nanospheres. Drug was administered to groups of pigs and rats via oral gavage of a suspension, and dicumarol concentration in the blood was measured using a double extraction technique.

Results. In vitro results showed improved dissolution in both the micronized formulation and the encapsulated p(FA:SA) nanospheres. In vivo, relative bioavailability of a spray-dried formulation was increased by 17% in the rat and 72% in the pig by further reduction in particle size. The bioadhesive p(FA:SA) formulation also improved relative bioavailability over the spray-dried drug, increasing it by 55% in the rat and 96% in the pig. Additionally, the p(FA:SA) formulation prolonged Tmax and decreased Cmax in both species.

Conclusion. This work demonstrates the importance of particle size and bioadhesion to improve oral bioavailability of ducumarol.

reducing particle size solid solution poly(fumaric-co-sebacic) anhydride bioadhesion poorly water-soluble drug 

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Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • C. G. Thanos
    • 1
  • Z. Liu
    • 1
  • J. Reineke
    • 1
  • E. Edwards
    • 1
  • E. Mathiowitz
    • 1
  1. 1.Department of Molecular Pharmacology, Physiology, and BiotechnologyBrown UniversityProvidence

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