Inhalation characteristics and their effects on in vitro drug delivery from dry powder inhalers: 1. Inhalation characteristics, work of breathing and volunteers' preference in dependence of the inhaler resistance

A test inhaler with exchangeable air flow resistances encompassing the range of commercial DPIs has been used to study the inspiratory flow curves of 39 healthy adult volunteers. A strong increase in mean Peak Inspiratory Flow Rate (PIFR) has been obtained with decreasing inhaler resistance, varying between 160 l/min for a resistance equivalent to the Rotahaler and 50 l/min for the simulated Inhalator Ingelheim at maximum inspiratory effort. The volunteers experienced on average 55% of maximum effort as comfortable (expressed in PIFR) and gave preference (82%) to relative high air flow resistances in the range of 0.4-0.9 x 10(5)(N-0.5. S . m(-4)). It has been calculated that the real amount of work of breathing does not increase with increasing air flow resistance at comfortable inspiration mode. At maximum inspiration, the amount of work performed through a high resistance inhaler (1.5 x 10(5)) is approx. 70% of that through a low resistance device (0.4 x 10(5)). The calculated mean PIFR of 62 l/min at maximum effort through an air flow resistance of 0.9 x 10(5), equivalent to the Turbuhaler, is in good agreement with PIFR-values of 68.5 vs. 59 l/min from two other studies with asthmatic patients through this device. It has, therefore, been concluded that the flow curves of healthy volunteers may be used to predict the range of PIFRs for asthmatics through the same air flow resistances.