Rectal versus oral absorption of diflunisal in man

Rectal absorption of diflunisal from various dosage forms was studied in man. The rectal dosage forms included fatty and macrogol suppositories, an aqueous suspension and solutions with various solvents in order to achieve complete dissolution of diflunisal. A comparison was made with an orally administered suspension. The plasma concentrations of diflunisal were measured by means of HPLC analysis after a single dose of 250 mg diflunisal in a cross-over study in 7 volunteers.

Compared with oral administration, rectal absorption conditions are limited as a consequence of the poor solubility characteristics of diflunisal. Therefore attempts were made to improve absorption conditions by varying the nature of the rectal dosage form. The addition of alkali and solvents such as polyethylene glycol and glycofurol, did result in an increase of the rate of absorption, whereas the bioavailability 8 h after administration did rise up to 80% as compared with oral dosing. In the case where suppositories are employed, a fatty vehicle rather than a water-soluble base should be chosen in order to stimulate the driving force for absorption. It is concluded that 500 mg diflunisal suspended in a 4 ml fatty mass results in peak plasma concentrations comparable with an oral dose of 250 mg diflunisal.