Hygroscopic Growth

The ability of drug-containing particles and droplets to exchange water with the atmosphere in the respiratory tract has been discussed so far only in the context of being a factor contributing to the loss in the useful fraction of the drug reaching the lung. However, theoretical models predict that hygroscopic growth may be used to enhance deposition of therapeutic aerosols [106-108]. Once again, theory is somewhat ahead of experimental work in this field. Good predictive models of hygroscopic growth require reliable information about the nature of the environment in the airways. There has been much interest in recent years in investigating the distribution of relative humidity and temperature in the respiratory tract [67,109-115]. If the aerosol is present in sufficient quantity, it can affect the relative humidity in the respiratory tract and hence its own hygroscopic growth. This was demonstrated in human deposition studies in which nonisotonic aqueous aerosols with identical initial particle size distributions and aqueous solution properties were used but the droplet number concentrations were different [73,74]. To be able to predict correctly the rate and extent of hygroscopic growth, it would appear that the rate of dissolution of drugs and their solution properties (without and with excipients) need to be determined, because the nonideal behavior of these solutions is likely to cause significant deviations from the growth dynamics predicted for simple inorganic salts [70,73,116,117].

Control of the hygroscopic growth rate may be achieved, for example, by preparation of drugs in solid forms with reduced aqueous solubility [102,103] or by coating the drug with hydrophobic films [118-120]. These formulation interventions can prevent hygroscopic growth altogether, if desired, because the growth rate will be retarded to the point where no enlargement would take place during the transit of the particle in the respiratory tract.

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