Inclusion mode of flurbiprofen with .BETA.-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-.BETA.-cyclodextrin, and improvements of some pharmaceutical properties of flurbiprofen by complexation.

Abstract

The inclusion behavior of flurbiprofen (FP) with heptakis(2,3,6-tri-O-methyl)-.beta.-cyclodextrin (TM-.beta.-CyD) in solution and in the solid state was compared with that of FP with .beta.-cyclodextrin (.beta.-CyD) by microcalorimetry and solid-state nuclear magnetic resonance (NMR) measurements. Furthermore, solid complexes of FP with .beta.-CyD and TM-.beta.-CyD were obtained in the molar ratio of 1:1, and their dissolution behavior, permeation through a silicone membrane and in vivo [rabbit] absorption behavior were examined, in comparison with those of FP alone. The data suggest that the inclusion behavior of FP with TM-.beta.-CyD is somewhat different from that with .beta.-CyD. The apparent rates of dissolution, permeation and the bioavailability of FP were significantly increased by the inclusion complex formation. However, no differences between the pharmacokinetic parameters were found for the two complexes. It is concluded that the enhanced bioavailability of FP after oral administration may be due to the fast dissolution of the complexes.