Formulation approaches to improving the delivery of an antiviral drug with activity against seasonal flu

Abstract

The main objective of the present study was to develop formulations of noscapine hydrochloride hydrate with enhanced solubility and bioavailability using co-solvent- and cyclodextrin-based approaches. Different combinations of co-solvents, which were selected on the basis of high-throughput solubility screening, were subjected to in vitro intestinal drug permeability studies conducted with Ussing chambers. Vitamin E tocopherol polyethylene glycol succinate and propylene glycol based co-solvent formulations provided the maximum permeability coefficient for the drug. Inclusion complexes of the drug were prepared using hydroxypropyl-β-cyclodextrin and sulphobutylether cyclodextrins. Pharmacokinetic studies were carried out in male Sprague–Dawley rats for the selected formulations. The relative bioavailabilities of the drug with the co-solvent- and cyclodextrin-based formulations were found to be similar.

• Bioavailability
• co-solvents
• cyclodextrins
• solubility
• Ussing chambers

Acknowledgements

The authors would like to thank Dr Joan-Huey Dow for HPLC analysis of formulation samples, Dr Robert Swezey for bioanalysis of the plasma samples and Mr. Paul Penwell for DSC determinations.

Declaration of interest

This project has been funded in whole or part with federal funds from NIAID, NIH, DHHS under Contract No. HHSN266200600011C/N01-AI-60011. The authors report no declarations of interest.