Influence of some surface-active agents on nasal absorption in rabbits

Abstract The nasal mucosa is a potential site for drug absorption, avoiding problems such as first-pass metabolism and/or gastrointestinal decomposition. The nasal route is especially important for the administration of hormones. However, the aid of absorption enhancers is sometimes required to achieve a high enough bioavailability. Until now, bile salts are the most frequent studied nasal absorption enhancers. The frequent use of bile salts as absorption promotors is limited by their local side-effects. Other, non-bile salt surfactants are currently under research for their efficacy and safety. In this study the effect of 6 different surfactants on the nasal absorption of a model compound (Phenol red) was determined in rabbits. Three bile salts, sodium taurodeoxycholate (TDC), sodium glycode-oxycholate (GDC), sodium deoxycholate (DC)) and 3 other surfactants (Cremophor-EL (CEL), polyoxyethylene-9-lauryl ether (BL-9) and sodium taurodihydrofusidate (STDHF)) were used. The concentration of most of the absorption enhancers in the nasal absorption experiment was 20 mmol 1 , for CEL and BL-9 it was 1% ( w v ) as their exact molecular weight is unknown. The influence of the absorption enhancers on the phenol red bioavailability was calculated from the serum curves. Phenol red serum concentrations were determined spectrophotometrically. It was found that the combination of Phenol red with the bile salts DC and with the ether-type surfactant BL-9 resulted in a fast and almost complete phenol red absorption, related to the intravenous standard ( F DC = 98 ± 36% and F BL-9 = 87 ± 20%). STDHF resulted in a relatively high bioavailability of f stqhf = 83 ± 18% b absorption was slow with a mean residence time (MRT) = 36 ± 6 min. The ester type surfactant CEL had no detectable influence on the nasal absorption; the bioavailability of the phenol red did not differ from the bioavailability of the blank administration F CEL = 21 ± 6% and F BLANK = 22 ± 11%. The ester may be hydrolysed in the nasal mucus, either by enzymes or bacteria present the mucus layer. Surfactant resistance to these degrading activities may be essential. The described procedure with Phenol red as a model compound proved to be suitable for nasal absorption studies.