Clearance characteristics of chitosan based formulations in the sheep nasal cavity

This paper describes the clearance characteristics of two bioadhesive nasal delivery systems in the form of chitosan microspheres and chitosan solutio n, from the nasal cavity of conscious sheep. The pattern of deposition and clearance of the nasal dosage forms were evaluated using a radioactive trac er and the non-invasive technique of gamma scintigraphy. The clearance of c hitosan microsphere and solution formulations was compared with that of a c ontrol solution. The data show that the control was cleared rapidly from th e sheep nasal cavity with a half-time of clearance (time taken for 50% clea rance; t(50%)) of about 15 min. The bioadhesive chitosan delivery systems w ere cleared at a slower rate, with half-times of clearance of 43 min and 11 5 min, for solution and microsphere formulations respectively. From the res ults reported in this study it can be concluded that the chitosan delivery systems investigated had significantly reduced rates of clearance from the sheep nasal cavity, as compared to the control. Consequently, chitosan deli very systems have the ability to increase the residence time of drug formul ations in the nasal cavity thereby providing the potential for improved sys temic medication. The nasal clearance rates recorded in the sheep model mim ic very closely the clearance rates found in a previous study using human s ubjects. It can also be concluded that the sheep can be considered a suitab le model for in vivo nasal clearance studies of novel bioadhesive drug deli very systems. (C) 2001 Elsevier Science B.V. All rights reserved.