Factors Influencing the Rate of Drug Output During the Course of Wet Nebulization

Abstract

Jet nebulization in an unvented nebulizer is a complex phenomenon which includes the physical fracturing of a liquid film into droplets of aerosol and the evaporative losses that accompany the interaction between the nebulizing gas and the nebulizer solution. The process of nebulization continues until a certain minimal residual volume (dead volume) is reached. This dead volume is determined by the loss of the liquid volume of the aerosol and the amount of evaporative losses, the latter partially determined by the relative humidity of the nebulizing gas. Evaporative losses are maximized if the nebulizing gas is free of water vapor and are minimized if it is wet, as is usually the case when room air is compressed but not dried. In order to explain differences in nebulizer output between dry and wet nebulizing gases, a mathematical model was developed that allows the calculation of the total output of drug, the liquid volume of aerosol, and the water loss due to evaporation, all with respect to time. The model was validated by comparing the actual output calculated from the initial nebulizer drug content minus that remaining in the nebulizer at specific points in time with that predicted by the model. The model demonstrated that the actual volume of liquid aerosol was dependent on the nebulizer type and the nebulizing flow but was independent of the water vapor content of the nebulizing gas. On the other hand, the evaporative losses were much greater when the nebulizing gas was dry was opposed to compressed room air, and the resultant drug output was less. This model allows the separation of the factors that govern aerosol output so that each can be studied individually.