Behavior of hygroscopic pharmaceutical aerosols and the influence of hydrophobic additives.

The high temperature and relative humidity in the lung can result in the hygroscopic growth of susceptible aerosol particles or droplets. The term hygroscopic growth describes the increase in particle diameter which occurs as the result of association with water vapor. The influence of hygroscopicity upon lung deposition of aerosols has been a productive area of research in industrial hygiene, environmental sciences, and inhalation toxicology. Many pharmaceutical inhalation aerosols display hygroscopic behavior in their passage through the airways; however, the effect has been neglected. Controlling the phenomenon of hygroscopic growth and, thus, the related lung deposition of aerosols might result in the therapeutic advantage of targeting the site of action. Such an approach might also allow identification of the location of pharmacologic receptor sites in the lung. This Review discusses an approach to achieving control of hygroscopic growth of aerosol particles. Theoretical and experimental studies have indicated that inhaled particle diameters increased significantly for drugs commonly administered to the lung. The presence of certain additives, notably glycerol, cetyl alcohol, and lauric and capric acids, has been demonstrated to reduce the growth of particles under conditions approaching those in the lung. Very few quantitative studies of the nature discussed herein have appeared in the literature. It is conceivable that an aerosol particle could be fabricated of known initial size and density, and by implication, deposition characteristic, and this might be induced to follow specific growth kinetics to enhance deposition in a particular region of the lung. Thus, physical targeting of regions within the lung might be achieved.