抄録
Flurbiprofen (FP), nonsteroidal antiinflammatory drug, is poorly soluble in water and sometimes causes an adverse reaction due to a stimulant property to stomach after oral administration. The inclusion complexes of FP with natural β-and γ-cyclodextrin (β-, γ-CyD) or methylated β-CyD, heptakis(2, 6-di-O-methyl)-β-CyD (DM-β-CyD) and heptakis(2, 3, 6-tri-O-methyl)-β-CyD (TM-β-CyD), in a 1:1 molar ratio were prepared, and then their dissolution, absorption characteristics and the irritation of the gastric mucosa of rats were compared with those of FP. The dissolution rate of FP from capsules in JP XI No. 1 was significantly increased by the inclusion complexation (γ->DM-β->β->TM-β-CyD complex>FP alone). The serum levels of FP following the oral administration in form of complex to rats are higher than after the drug alone (DM-β-≈γ->β->TM-β-CyDcomplex> FP alone). The gastric damages induced by a single administration of complexes with β-, γ-and TM-β-CyD were less than that of FP alone, while gastric damage induced by DM-β-CyD complex was same as FP alone. The enhanced bioavailability and reduced gastric damage of FP by complexation with natural β-and γ-CyD suggested the possibility of smaller doses and fewer adverse effects in FP therapy.
