Preparation and Evaluation of Eudragit Gels. VIII. Rectal Absorption of 5-Fluorouracil from Eudispert hv Gels in Rats

Abstract

Rectal absorption of the hydrophilic 5‐fluorouracil (5‐FU) in rats was studied with Eudispert hv gels with or without fatty acids as the rectal bases. In the absence of fatty acids, absolute bioavailabilities of 5‐FU for Eudispert hv hydrogel and xerogel preparations increased ˜2.5 times compared with those of Witepsol H‐15 and PEG 2000 suppositories. Whenn‐capric acid or linolenic acid was used as an absorption enhancer, absolute bioavalabilities of 5‐FU were, respectively, 25.5 and 30.9% for Witepsol H‐15 and 64.4 and 66.1% for PEG 2000. Furthermore, the absolute bioavailabilities of 5‐FU for Eudispert hv hydrogel withn‐capric acid or linolenic acid were 95.6% and 81.7%. The addition of capric acid or linolenic acid to the hydrogel was a useful method for increasing 5‐FU permeability through the rectal membranes. These results are consistent with the observation that the total amounts of 5‐FU remaining in the lumenal contents of the rectum and that accumulated in the rectal tissue decreased in relation to the increase in the bioavailabilities. Thus, the Eudispert hv hydrogel containing 5‐FU with capric acid may be a useful rectal preparation for increasing the maximum plasma level and improving the absolute bioavailability of 5‐FU.