The Impact of Dry Powder Inhaler Performance of Testing Using Pharmacopeial Methodology Compared to More Realistic Testing Conditions

Monbi Chakma


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.

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