Development of a new non-surgical perfusion technique for evaluation of nasal drug delivery.
A new non-surgical perfusion technique was developed to evaluate nasal absorption using the rabbit as an animal model and insulin as a model drug. For these studies 20 ml of insulin solution (10 U/kg + 0.05% Na taurocholate) was perfused for 3.5 hours at a rate of 10 ml/hr. Spray formulations containing different levels of insulin (1.25, 2.5, 5 and 10 U/kg) and sodium taurocholate (0.05 and 1.0%) were evaluated in the same animal model. Insulin loaded polyacrylic acid microparticles were administered in 1% gel formulation to determine the comparative effect of insulin. The absorption of insulin was measured by glucose reduction. Pharmacodynamic parameters were determined relative to subcutaneously injected insulin (0.25 U/kg). The new non-surgical perfusion technique proved to be easier to control and more reproducible than the formerly used perfusion model while providing comparable results. The maximum relative absorption was observed for the 1.25 U/kg spray containing 1% NaTC. The polyacrylic acid gel formulation containing insulin loaded microparticles (10 U/kg) resulted in lower hypoglycemic effect compared to the spray formulations and subcutaneous injection.