DOSE EMISSIONS FROM MARKETED DRY POWDER INHALERS

The dose emission characteristics of eight marketed dry powder inhalers (DPIs: Intal Spinhaler(R), Ventolin and Becotide Diskhalers(R), Ventolin and Becotide Rotahalers(R), Bricanyl and Pulmicort Turbohalers(R), Berotec Inhalator(R)) have been investigated using the proposed USP dosage unit sampling apparatus for DPIs. Intra- and inter-device variation in emitted doses was determined at air flow rates of 60 and 100 l/min using a 4 lair throughput in each case except Inhalator(R), which was tested at 30 l/min only. The sampling apparatus was found to be suitable for quantifying single emitted doses from all of these devices which comprise examples of low, medium and high airflow resistance DPIs (Table 1 footnote). Dose emissions from the DPIs are presented as percentages of the manufacturers' label claims. Under all test flow conditions variability was high, when compared to the uniformity of content standards usually applied to pharmaceutical products; in some cases relative standard deviations (RSD) were greater than 15%, both within and between devices. However, under the proposed USP test flow rate conditions, the total RSD (n = 25) was < 15% around the average emitted dose in all cases except Pulmicort Turbohaler(R); such variance (RSD < 15%) is proposed to be acceptable for DPIs delivering current medications. Only the Intal Spinhaler(R) emitted an average dose similar to its label claim. Testing at 100 l/min vs 60 l/min significantly increased DPI drug emission and reduced the device retention of both the Ventolin(R) and Becotide(R) versions of the low resistance devices, Rotahaler(R) and Diskhaler(R). Using these same flow rates for testing the dose emissions from the medium resistance Bricanyl and Pulmicort Turbohalers(R), there was no significant difference in drug output between the two flow rates.