Improved oral bioavailability of fexofenadine hydrochloride using lipid surfactants: ex vivo, in situ and in vivo studies

Abstract

The aim of the present study was to improve the dissolution, permeability and therefore oral bioavailability of the fexofenadine hydrochloride (FEX), by preparing lipid surfactant based dispersions using self-emulsifying carriers, i.e. Gelucire 44/14 (GLC) and d-α-tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS or TPGS). The reprecipitation studies were conducted using these carriers to evaluate inhibition of reprecipitation by maintaining super saturation state. The aqueous solubility of the FEX was increased linearly with increasing GLC, TPGS concentrations as verified by the phase solubility studies. The dispersions of FEX were prepared in different drug/GLC (GD) and drug/TPGS (TD) ratios by melt method and evaluated. The prepared dispersions showed improved dissolution rate in distilled water as dissolution media and highest dissolution rate was achieved with dispersions prepared using TPGS. The solid state characterization was carried by differential scanning calorimetry and scanning electron microscopy indicated reduced crystallinity of the drug. Fourier transform infrared spectroscopy revealed the compatibility of drug with carriers. The ex vivo permeation studies conducted using intestinal gut sac technique, resulted in reduced efflux of the drug by inhibiting intestinal P-glycoprotein from the dispersions. The in situ perfusion studies and in vivo pharmacokinetic studies in male wistar rats showed improved absorption and oral bioavailability from the prepared dispersions as compared to pure drug.

• Bioavailability
• dissolution
• fexofenadine hydrochloride
• Gelucire 44/14
• permeation
• vitamin E TPGS

Acknowledgements

The authors would like to thank Ami Life Sciences Pvt. Ltd, Gujarat, India for the generous gift sample of fexofenadine hydrochloride. The authors are also grateful to Gattefosse, France and Isochem, France for the donation of excipients. The financial assistance to Basanth Babu Eedara by All India Council of Technical Education (New Delhi, India) in the form of Junior Research Fellowship is duly acknowledged. The authors also thank Mr. T. Jayapal Reddy, Chairman, St. Peter’s Institute of Pharmaceutical Sciences, Hanamkonda for providing the necessary facilities.