Oral bioavailability enhancement of flubendazole by developing nanofibrous solid dosage forms

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
• electrospinning
• bioavailability
• dissolution
• downstream
• amorphization
• immediate release

Acknowledgements

A strong foundation of this work was the stimulating professional enthusiasm of Dr. Marcus E. Brewster, former Vice President and Scientific Fellow at Janssen Research and Development.

The authors are indebted to Éva Kiserdei for her outstanding technical support. This work is connected to the scientific program of the “Development of quality-oriented and harmonized R + D+ I strategy and functional model at BME” project. The authors mean to express their gratitude to Dr János Madarász (Budapest University of Technology and Economics, Hungary) for making XRD measurements possible in his laboratory.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This project is supported by the New Széchenyi Plan (Project ID: TÁMOP-4.2.1/B-09/1/KMR-2010–0002), by OTKA research fund [grant number K112644], and by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences.