Design and in vitro performance testing of multiple air classifier technology in a new disposable inhaler concept (Twincer) for high powder doses.

Dry powder inhalation of antibiotics in cystic fibrosis (CF) therapy may be a valuable alternative for wet nebulisation, because it saves time and it improves lung deposition. In this study, it is shown that the use of multiple air classifier technology enables effective dispersion of large amounts of micronised powder (up to 25mg). X(50)-values of the aerosol from laser diffraction analysis obtained with the Twincer disposable inhaler concept (containing multiple air classifier technology) are practically the same as that for the pure drug in the range of dose weights between 0 and 25mg. Only for the highest dose weights, a minor fraction (5-7.5%) of small agglomerates (5-15microm) is released from the inhaler. Moreover, the size distribution of the aerosol is practically the same at 1 and 4kPa. Cascade impactor results confirm the good performance of the multiple classifier concept. Unprocessed micronised particles or soft spherical agglomerates can be used, and special particle engineering processes are not necessary. Only a minor fraction of coarse sweeper crystals in the formulation is desired to reduce the total inhaler losses for colistin sulfomethate to less than 5-6% at 4kPa. The classifiers can be designed to retain these crystals with more than 95% efficiency.