R. Jashnani, P. Byron
Mar 15, 1996
Citations
2
Influential Citations
43
Citations
Journal
International Journal of Pharmaceutics
Abstract
Abstract Aerosols formed by three salts and the free base of albuterol were compared following their formation from similarly micronized crystalline powders held in a model dry powder inhaler (DPI) under varying environmental conditions. Aqueous solubility at 22°C was the greatest for albuterol adipate diethanolate (353 mg/ml), followed by albuterol sulfate (250 mg/ml), albuterol free base (15.7 mg/ml) and albuterol stearate (0.6 mg/ml). Temperature and relative humidity (RH) of the air drawn through the inhaler was systematically varied in the range 20–45°C and 30–95% RH. Several inhaler performance outcomes were compared statistically between physical forms and across the applied environmental conditions. Significant differences (P 0.05) although only albuterol adipate diethanolate and albuterol sulfate were insensitive at 94% RH and 45°C. At 20°C and 50% RH, the fine particle percent of the emitted doses [mean (experimental range)] were 77.7 (7.3)%, 63.6 (4.2)%, 9.0 (1.8)% and 55.7 (3.4)% for the free base, sulfate, adipate diethanolate and stearate salts of albuterol, respectively. Fine particle doses and percents of albuterol and albuterol sulfate decreased progressively with increasing relative humidity and temperature while albuterol adipate diethanolate and albuterol stearate aerosol performance remained largely unaffected; these latter salts showed changes in fine particle percents only at 45°C and 95% RH although the adipate diethanolate deaggregated very poorly under all conditions. Overall, albuterol stearate, the most hydrophobic salt, emptied and aerosolized best from the inhaler and showed least sensitivity to temperature and humidity. Neither solubility nor moisture sorption correlated directly with inhaler performance in high humidity environments, showing that the multiplicity of factors controlling the quality of the emitted aerosol from DPIs prevents straightforward prediction of optimal physical forms and mandates their experimental review. Nevertheless, salt selection is an important area to screen as new compounds are developed for inhalation and DPI device performance continues to improve.