EVALUATION OF ENHANCERS TO INCREASE NASAL ABSORPTION USING USSING CHAMBER TECHNIQUE

The effects of eight prospective absorption enhancers on the nasal muc osa in rabbit have been assessed using an in vitro Ussing chamber tech nique. Sodium taurodihydrofusidate (STDHF), sodium deoxycholate (DC), polyoxyethylene-9-lauryl ether (BL-9), lysophosphatidylcholine (LPC) a nd sodium dodecyl sulfate (SDS) were found to possess relatively high protein leaching activity, while sodium glycocholate (GC), sodium taur ocholate (TC) and EDTA had relatively low activity. The permeation of fluorescein isothiocyanate-labeled dextran (FD, M.W. 9400) as a model drug across the nasal mucosa was found to be greater in the presence o f these enhancers. Their enhancement ratio was found to be in the orde r of BL-9 > STDHF > SDS > LPC > DC > EDTA > GC > TC, which correlated with the protein leaching activity. The differences in protein leachin g and enhancement ratio dependent on the magnitude of change of membra ne resistance (Delta Rm), indicating that these enhancers damaged the membrane and increased FD permeation. Delta Rm thus appears to be a us eful indicator by which one can estimate nasal mucosa damage by the en hancers.