Summary
Current procedures implemented by regulators to assess dry powder inhaler (DPI) performance in-vitro utilise pharmacopeial inhalation profiles. The European Pharmacopeia (EP) requires an inhalation volume of 4 L at a constant pressure of 4 kPa to achieve sufficient de-aggregation of the dry powder through the impactor. However, as humans do not inhale at a constant rate, the recommended flow rates may produce misleading in-vitro results and thus, will not correlate in-vivo. Consequently, compromised patients with chronic obstructive pulmonary disease (COPD) may not achieve the necessary 4 L inhalation volume and thus, the delivered dose may differ significantly to that in-vitro.
To investigate in-vitro in-vivo correlation (IVIVC), pharmacopeial profiles were used to represent weak, medium and strong inhalation (30, 60 and 90 L/min) whereas, 10th and 50th percentiles from COPD patient data were assigned as weak and medium respectively. Seretide® and AirFluSal® were investigated in terms of total emitted dose (TED) which quantified the amount of salmeterol xinafoate (SX) and fluticasone propionate (FP) per actuation (n=10). Aerodynamic size distribution was also assessed stage by stage using the NGI (n=3), including fine particle fraction (FPF), mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD).
Although both inhalers exhibited bioequivalence assessed by stage deposition within ± 15% variability, significant differences were observed for impactor stage deposition at 30 L/min and when using the weak inhalation profile (p<0.05). The MMAD and FPF for each inhaler differed when flow rates increased from 30-60 L/min (p<0.05) but no difference was observed for 60-90 L/min.
