Biopharmaceutical study of inclusion complexes. I. Pharmaceutical advantages of cyclodextrin complexes of bencyclane fumarate.

Abstract

Complexes of bencyclane fumarate (Ben) with cyclodextrins (CD) were newly prepared and their characteristics were studied from a pharmaceutical viewpoint. The results of differential scanning calorimetry (DSC), X-ray diffractometry and TLC were consistent with the formation of inclusion complexes. Water solubility of Ben-CD were 2- to 8-fold larger than that of Ben. The stability of Ben in acidic media (pH 1.2) was considerably improved by complex formation with .beta.-CD or .gamma.-CD. Apparent 1st-order rate constants [h-1] of hydrolysis of Ben were 6.5 .times. 10-2, 5.5 .times. 10-2, 1.0 .times. 1.0-2, and 1.7 .times. 10-2 for Ben, Ben-.alpha.-CD, Ben-.beta.-CD and Ben-.gamma.-CD, respectively. The intrinsic bitter taste of Ben was significantly reduced by inclusion complexation with CD. There are clear pharmaceutical advantages of Ben-CD compared with Ben. A novel rabbit test method, which is helpful for studying astringent bitter-tasting drugs, is proposed.