Abstract
Powder formulations of fluorescein were prepared with carriers, including microcrystalline cellulose (MCC), hydroxypropylcellulose (HPC), and lactose or polystyrene particles (PP), and administered to rabbits intranasally. The order of fluorescein absorption in terms of the AUC was MCC > PP > HPC > lactose. To clarify the differences between the carriers, absorption and elimination of fluorescein from the nasal cavity were simultaneously determined using a newly developed in vivo method. Elimination of carriers was also determined by the method. To quantify insoluble MCC and PP, a new image-analysis method was developed. These results, with in vitro fluorescein release studies, suggest that the schematic role of carriers in nasal delivery is as follows. Both MCC and PP are insoluble and showed rapid fluorescein release. PP was eliminated rapidly, while MCC was retained in the cavity. This suggests that bioadhesive MCC probably forms a local environment with a higher fluorescein concentration between the particles and membrane, thus resulting in enhanced absorption. In the HPC formulation, fluorescein or HPC eliminations and fluorescein release were sustained due to its gel-forming property. In the lactose formulation, lactose dissolves rapidly, and there may be no means for fluorescein to stay near the mucous membrane. As a result, fluorescein was eliminated rapidly by mucus flow, thus resulting in poor absorption.
