Effects of Cyclodextrin Derivatives on Bioavailability of Ketoprofen

Abstract

In order to develop a new oral dosage form of ketoprofen with enhanced dissolution rate and bioavailability, inclusion complexes of ketoprofen with cyclodextrin derivatives such as α-cyclodextrin, β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, and dimethyl-β-cyclodextrin were prepared using a spray dryer, and comparative studies on the in vitro dissolution and in vivo absorption of ketoprofen were carried out. Ketoprofen in the inclusion complexes was completely dissolved within 5 min. On the other hand, only about 50.1% of ketoprofen powder alone dissolved in 60 min. The initial dissolution rates of ketoprofen in the inclusion complexes markedly increased in distilled water at 37°C, which were over 5-fold higher than that of powder alone. The maximal plasma concentration of ketoprofen (Cmax) and area under concentration-time curve (AUC0→8h) after the oral administration of inclusion complexes increased about 6-fold (46.69 or 45.36 vs. 7.55 μ/ml) and 3-fold (44.41 or 50.14 vs. 17.33 μ hr/ml) compared to those of powder alone. It was obvious that ketoprofen inclusion complex might be a useful solid dosage form in improving the dissolution rate and bioavailability of poorly water-soluble ketoprofen.