Effect of viscosity on particle size, deposition, and clearance of nasal delivery systems containing desmopressin

Abstract

The effect of methylcellulose on the particle size distribution and dosing accuracy of pre-metered spray pump devices containing the peptide desmopressin (DDAVP) was investigated. Using gamma scintigraphy, the influence of methylcellulose on the in vivo deposition and clearance of nasal solutions administered as drops or spray was studied. Nasal formulations containing 0, 0.25, and 0.50% methylcellulose produced a dose-related increase in average particle size from 51 micron for 0% to 81 and 200 micron for 0.25 and 0.50% methylcellulose, respectively. However, no effect was observed on the dosing accuracy of the spray pumps. The addition of methylcellulose gave a more localized in vivo deposition in the anterior region of the nasal vestibule. However, the net effect on clearance followed a biphasic pattern which showed an increase in retention time for the 0.25% solution, followed by a decrease in retention time and faster clearance time for the 0.50% solution. The spray delivers well-controlled doses to the nasal cavity. These findings show that viscosity, particle size, and nasal clearance are important parameters in the design of nasal delivery systems.