Oral bioavailability enhancement of flubendazole by developing nanofibrous solid dosage forms

Drug Dev Ind Pharm. 2017 Jul;43(7):1126-1133. doi: 10.1080/03639045.2017.1298121. Epub 2017 Mar 8.

Abstract

The bioavailability of the anthelminthic flubendazole was remarkably enhanced in comparison with the pure crystalline drug by developing completely amorphous electrospun nanofibres with a matrix consisting of hydroxypropyl-β-cyclodextrin and polyvinylpyrrolidone. The thus produced formulations can potentially be active against macrofilariae parasites causing tropical diseases, for example, river blindness and elephantiasis, which affect altogether more than a hundred million people worldwide. The bioavailability enhancement was based on the considerably improved dissolution. The release of a dose of 40 mg could be achieved within 15 min. Accordingly, administration of the nanofibrous system ensured an increased plasma concentration profile in rats in contrast to the practically non-absorbable crystalline flubendazole. Furthermore, easy-to-grind fibers could be developed, which enabled compression of easily administrable immediate release tablets.

Keywords: Nanofiber; amorphization; bioavailability; dissolution; downstream; electrospinning; immediate release.

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Administration, Oral
  • Animals
  • Biological Availability
  • Chemistry, Pharmaceutical
  • Crystallization
  • Mebendazole / administration & dosage
  • Mebendazole / analogs & derivatives*
  • Mebendazole / chemistry
  • Nanofibers / chemistry*
  • Povidone / chemistry*
  • Rats
  • Tablets / chemistry*
  • beta-Cyclodextrins / chemistry*

Substances

  • Tablets
  • beta-Cyclodextrins
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Mebendazole
  • Povidone
  • flubendazole