A Novel Dry Powder Aerosol Delivery System for Real Time Measurement of the Inhaled Dose to Large Animals (Dogs)

ABSTRACT

Pharmaceutical drugs can be administered by inhalation to experimental animals as a dry powder aerosol. In such experiments the aerosol is continuously generated from a dry powder generator and inhaled by the experimental animal. The drug delivery system can be used to study the effects of drugs either locally, in the airways and lung, or systemically. With conventional methods, however, it has not been possible to measure the inhaled mass and calculate the accumulated inhaled dose nor to perform the measurements in real time. The method evaluated here, called FIDO, was thus developed to more accurately estimate an inhaled dose than the methods used previously. To validate the feasibility of FIDO, it was compared with two conventional filter methods. Inhalation studies on five dogs were performed at three different aerosol concentrations corresponding to low, medium, and high inhaled doses. The dogs were exposed in a random manner four times at each dose level. In separate studies the generator performance along with the dog minute volume variation and their influence on the accuracy of FIDO was also investigated. A statistical evaluation of the results was done, comparing the analytically determined mass on filter, from the dog studies, with the inhaled dose estimated by the two conventional filter methods and the inhaled dose measured by FIDO. For each method, the mean value, 95% confidence interval, and standard deviation was computed. The data obtained supports the hypothesis that FIDO seems to be more accurate in calculating the inhaled dose compared to the other two methods.