Enhancement of Aqueous Solubility and Oral Bioavailability of Nelfinavir by Complexation with β- Cyclodextrin

Purpose: To determine if complexation with β- cyclodextrin (β-CD) increases water solubility and subsequent bioavailability of nelfinavir mesylate (NM).
Methods: Complexation of NM with β-CD in 1:1.5 molar ratio was carried out by solvent evaporation, freeze-drying and kneading methods. The complexes were characterized by Fourier transform infrared spectroscopy (FTIR). The in vitro solubility of the pure drug as well as that of the complexes was evaluated using USP type 2 apparatus. One of the drug complexes was also evaluated in vivo using Wistar rats to determine its pharmacokinetic profile.
Results: Freeze-dried NM-βCD complex was selected for in vivo studies based on its free flowing property and superior texture. The complexes prepared by the three methods all showed largely similar dissolution rate. The in vivo pharmacokinetic study of the freeze-dried complex in male Wistar rats showed significant increase in Cmax, tmax and AUC (p ≤ 0.05) compared to those of the plain drug.
Conclusion: These findings suggest that complexation of NM with β-CD is an effective and promising approach to increasing the oral bioavailability of NM.

Keywords
β-Cyclodextrin; Nelfinavir mesylate; Inclusion complex; Freeze-drying; Bioavailability; Dissolution; Kneading