Flow early in the inspiratory manoeuvre affects the aerosol particle size distribution from a Turbuhaler

Abstract

Several in vitro and in vivo studies have emphasized the importance of generating a high inspiratory flow when using a dry powder inhaler. Little attention has been paid to the influence of the inspiratory flow profile on the particle size distribution contained in aerosols generated by these devices. The internal volume of a device such as the Turbuhaler is small compared with a vital capacity breath and it is possible that all the powder has been drawn from the device before peak inspiratory flow has been achieved, particularly if the time to peak inspiratory flow is prolonged. A series of experiments were performed to assess the effect of different flow profiles through the Turbuhaler, each with a peak flow of 60 1 min-1. A 400 microgram budesonide Turbuhaler was enclosed in a chamber allowing air to pass unimpeded through the dosing channels and entrainment ports. A large three-way tap was used to blow powder from the device across a Malvern Mastersizer laser particle sizer which produced a profile of the particle size distribution within the aerosol. The rate of increase in flow through the Turbuhaler was determined by the rate at which the three-way tap was turned, and recorded by means of a pneumotachograph. The rate of increase in flow was found to significantly affect the particle size-distribution within the aerosol. Failure to attain a flow of 30 1 min-1 before 150 ml of air had passed through the device resulted in the aerosol volume median diameter increasing from less than 6.6 microns to greater than 45.3 microns. These results indicate that flow during the initial part of the inspiratory effort may be important in determining the characteristics of the aerosol generated by a dry powder inhaler. With more sophisticated equipment, it might be possible to explore the relationship between flow profile and particle size distribution generated by dry powder devices in more detail.

What the pulmonary specialist should know about the new inhalation therapies

“…It has been shown that de-agglomeration of particles takes place inside the device before the metered dose leaves the DPI and is increased if the acceleration is fast at the start of inhalation [65]. Thus, the FPD will be greater and the MMAD smaller when the initial acceleration rate of the inhalation flow is fast [65,66]. Hence patients should be instructed to inhale forcefully from the beginning of their inhalation.…”

The Inhalation Characteristics of Patients When They Use Different Dry Powder Inhalers

“…The acceleration of the flow, like the pressure change, has been shown to be critical for deaggregation of the formulation in a DPI, (14,15) because the dose is emitted in the first part of an inhalation. Overall, when the PIF was fast, then the acceleration rates were steeper than when the PIF was slow.…”

“…(5) Hence, more attention needs to be directed to the minimum acceptable PIF achieved through each DPI rather than to the optimal flow. Also, it has been suggested that the pressure changes that occur inside the inhalation channel of each DPI (13) and the initial acceleration rate of the inhalation maneuver (14,15) are more important than PIF in the generation of the fine particle dose. Similarly, inhaled volume is also considered an important parameter of the inhalation profile and can govern the quality of the emitted dose, (15) particularly in a capsule formulation (10,16) because of the need to empty the capsule.…”

The ADMIT series - Issues in Inhalation Therapy. 6) Training tools for inhalation devices

“…As mentioned, both the speed and the acceleration of the inspiratory manouevre when using a DPI critically affect the respirable dose. 8,16 Although the In-CheckDial does not measure the speed of inhalation, Broeders and colleagues have shown that it correlates with PIF when patients use DPIs.…”