Revisiting hygroscopic growth of nebulized pharmaceutics during inhalation: A novel strategy to use single droplet analysis to design nebulizer formulations for targeted dosing

A.E. Haddrell, J.F. Davies, R.E.H. Miles, L.A. Dailey, D. Murnane, J.P. Reid

Hygroscopic growth of nebulized pharmaceutics is believed to be minimal as the range of relative humidity experienced by a nebulized aerosol is thought to be saturated from generation to inhalation. However, recent studies have challenged this core belief. Shown here is that nebulized pharmaceutics experience a range of relative humidities, and the potential to improve the drug efficacy of existing pharmaceutics by controlling their hygroscopic properties through the tailoring the starting formulations for targeted deposition within the lung.
Three different single droplet analysis techniques were used to analyze existing nebulizer formulations. These techniques were used to measure the necessary water activity/mass fraction of solute and water activity/density relationships to accurately model rapid droplet mass flux, and to experimentally verify the aerosol dynamic model.
The improved hygroscopic growth data were then used to predict the aerodynamic diameter of a population of polydisperse droplets from nebulization to inhalation. The treatment of the aerosol prior to inhalation (ie. changes in the relative humidity, etc.), were modelled. The size of the aerosol was input into a whole lung model based on the International Commission on Radiological Protection lung model. When integrated with the starting number density of a nebulized aerosol, the overall dose was estimated. The makeup of the starting formulation and the treatment of the aerosol prior to inhalation, were found to have a profound effect on both the overall amount and site of the dose, demonstrating the need to investigate the influence of hygroscopic response on lung deposition more completely.

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