Developing a reliable multiple-dose dry powder inhaler (MDDPI) that can be adapted by patients would potentially improve dose delivery by use of the correct technique and dosing compliance. Adequate inspiratory flow rate (IFR) is required for optimal delivery of drugs formulated in dry powder. This study assessed the peak inspiratory flow rates (PIFR) of patients with asthma and chronic obstructive pulmonary disease (COPD) using a novel MDDPI (ForadilR CertihalerTM) to determine the effect of IFR on expected drug delivery.
In vivo and in vitro evaluations were performed. PIFR was assessed in children (5-19 yrs; n=42) and adults (20-76 yrs; n=41) with mild-severe asthma, and in adults with moderate-severe COPD (FEV1<60% predicted; 59-84 yrs; n=13) using an inhalation profile recorder. The highest of three successive inhalations was recorded. Delivered dose (DD) and fine particle fraction (FPF) were determined. Aerodynamic particle size distribution was assessed using an Anderson Cascade Impactor.
Mean (range) PIFRs in L/min were 63 (44-79), 70 (56-95), 63 (45-80) for children, adolescents and adults with asthma and 61 (51-78) for COPD patients. The release threshold for breath actuation was approximately 35 L/minute. Testing over inspiratory flow rates of 30-90 L/min showed that the in vitro delivered dose (DD) and fine particle fraction (FPF) were consistent over the entire range. DD in the range of observed PIFR of 40-90 L/min was 98.8-106.8% of an asthma label claim. Aerodynamic particle size distribution was marginally affected by flow rates. There was also little flow rate dependence of the FPF over clinically relevant ranges of IFR.
In vitro delivery characteristics of ForadilR CerthalerTM over clinically relevant flow rates were consistent and reproducible.
These findings suggest that delivery of formoterol via a novel MDDPI is reliable over a range of clinically relevant flow rates in patients with mild-moderate asthma and moderate-severe COPD.
U. Yegen, Novartis Pharmaceuticals AG and SkyePharma