Enhancing the oral bioavailability of the poorly soluble drug dicumarol with a bioadhesive polymer

✍ Scribed by Chris G. Thanos; Zhi Liu; Moses Goddard; Joshua Reineke; Nicola Bailey; Matthew Cross; Roxanne Burrill; Edith Mathiowitz

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 237 KB
• Volume: 92
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.10446

✦ Synopsis

This article investigates the effect of particle size and the incorporation of a bioadhesive polymer, poly(fumaric-co-sebacic) anhydride p(FA:SA), on the relative bioavailability of dicumarol. A novel method was used to reduce particle size of the drug, and encapsulated formulations were fabricated using a phase inversion technique to produce nanospheres and microspheres with varying size. Groups of Yorkshire swine were catheterized and gavaged after fasting for 12 h with each formulation in a 50 mg/mL suspension. Blood was collected at different time points, from 0 to 96 h, and pharmacokinetic analysis revealed that formulations incorporating the smaller drug particles showed the highest bioavailability: micronized drug with 7% p(FA:SA) 17:83 polymer had 190% relative bioavailability, and phase inverted p(FA:SA) 17:83 microspheres with 31% (w/w) loading had 198% relative bioavailability to spray dried formulation. Formulations with larger drug particles achieved 71% relative bioavailability. A nonadhesive formulation, fabricated with poly(lactic acid) (PLA), showed 91% relative bioavailability. Both particle size and polymer composition play a role in oral absorption of dicumarol.