BIOAVAILABILITY OF DANAZOL-HYDROXYPROPYL-BETA-CYLODEXTRIN COMPLEX BY DIFFERENT ROUTES OF ADMINISTRATION

Bioavailability of danazol-hydroxypropyl-beta-cyclodextrin complex was investigated in rats and dogs using different routes of administratio n. The complex was administered buccally in an aqueous solution form t o rats in which the esophagus had been ligated to prevent swallowing o f the complex, while oral administration was by gastric gavage. In dog s, the complex was administered buccally in the form of rapidly dissol ving adhesive patch formulation, and orally in the form of hard gelati n capsules. Buccal absorption of the complex was evaluated in an attem pt to bypass presystemic elimination. Buccal absorption of danazol in rats was slow and mean plasma concentration exhibited a plateau for 5 h. However, the extent of absorption was higher than the oral route, a nd bioavailability was 186% relative to oral administration. The absol ute bioavailability was 26.4%, indicating incomplete absorption of the complex after buccal administration. Plasma profiles and pharmacokine tic parameters obtained in dogs were similar in the orally and buccall y administered doses, suggesting that drug release from the buccal pat ch was not slow enough and the drug was consequently swallowed rather than absorbed across the buccal mucosa. Copyright (C) 1996 Elsevier Sc ience B.V.