Inclusion Complexes of Ketoprofen with β-cyclodextrins: Oral Pharmacokinetics of Ketoprofen in Human

The inclusion behavior of hydroxypropyl β-cyclodextrin and natural β-cyclodextrin was studied toward ketoprofen, in order to develop a new oral dosage form with enhanced dissolution rate and bioavailability, and to study the oral pharmacokinetics of ketoprofen in humans, following cyclodextrin complexation. Drug-cyclodextrin solid systems were prepared by kneading, co-evaporation, and freeze-drying. The formation of inclusion complexes with β­ cyclodextrin and hydroxypropyl β-cyclodextrin in the solid state, were confirmed by differential scanning calorimetry, Fourier transform infrared spectroscopy, powder X-ray diffractometry, scanning electron microscopy studies, and comparative studies on the in vitro dissolution and in vivo absorption of ketoprofen in humans volunteers, were carried out. The initial dissolution rate of ketoprofen in the inclusion complexes was 15 fold higher, than that of plain drug powder. The maximal plasma concentration of ketoprofen after the oral administration of inclusion complexes to human volunteers increased about 1.5 fold (7.15 vs 4.65 μg/ml), and there was no significant increase in area under concentration-time curve, AUC0-5 (10.35 vs. 9.35 μg. hr/ml), compared to those of ketoprofen powder alone.