Testing of dry powder aerosol formulations in different environmental conditions

Abstract

Dry powder aerosol performance of albuterol and albuterol sulfate from a model dry powder inhaler (DPI) was studied under varying environmental conditions using a twin stage impinger (TSI). Pure micronized drug was metered into the DPI and the loaded inhaler inserted into the inlet of the TSI housed in a pre-equilibrated environmental chamber. After 3 min, the drug was aerosolized at 60 1/min for 20 s. Washings from the DPI and TSI were analyzed by UV spectroscopy. Temperature and relative humidity (RH) were varied (20, 30 and 45°C; 30–95% RH). Drug collected in stage 2 of the TSI was expressed as fine particle dose or fine particle percent of either the loaded dose or the amount emitted from the mouthpiece of the DPI. These values decreased with increasing relative humidity for both albuterol and albuterol sulfate at any given temperature with differences being more marked at higher temperatures. For example, at 30°C, the mean(experimental range) fine particle percent of the emitted dose of albuterol sulfate was 59.4(3.1) and 35.8(5.7)% at 43 and 85% RH, respectively, n = 3 (p < 0.05). Increasing temperature also resulted in diminished aerosol performance. These differences were more marked for albuterol sulfate. The fine particle percent of the emitted dose of albuterol base was always greater than that of albuterol sulfate under similar environmental conditions. The reverse was true when fine particle percents of the loaded dose were considered because only 32 +- 6.6% of the loaded albuterol was emitted from the inhaler as compared to 58.5 +- 6.3% of albuterol sulfate mean +- SD, n = 27). There is a need, in some circumstances, to define specific ranges of temperature and humidity for the testing of dry powder aerosols.