Influence of Realistic Inspiratory Flow Profiles on Fine Particle Fractions of Dry Powder Aerosol Formulations

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Abstract

Purpose

The purpose of the study was to determine how air flow profiles affect fine particle fractions (FPF) (<5 μm) from dry powder aerosol formulations and whether laser diffraction (LD) could be used to measure FPF of aerosols generated by variable flows.

Materials and Methods

Carrier-based formulations containing 1.5% w/w micronized salbutamol base blended with the 63-90 μm fraction of alpha-lactose monohydrate or sorbitol or maltose were aerosolised from a model glass device using either a constant flow rate or a predetermined flow profile. The FPFs of the same aerosolised particles were first measured by LD and then by a liquid impinger. Volunteer inhalation airflow profiles and 3-phase (acceleration, constant flow rate and deceleration) square wave airflow profiles were generated using the Electronic Lung™ and an Inhalation Profile Recorder. Similar experiments were conducted for a carrier-free formulation from the Bricanyl Turbohaler™.

Results

Salbutamol FPFs of all carrier-based formulations were found to increase by increasing the initial flow increase rate (FIR) from 200 to 600 l min−1s−1although they could be placed in an increasing order of maltose blend < sorbitol blend < lactose blend. A significant linear correlation was found between FPFs measured by LD and by inertial impaction (R2=0.95, p<0.01, ANOVA). For the Bricanyl Turbohaler™, increasing FIR from 120 to 600 l min−1s−1for a constant peak flow rate (PFR) of 60 l min−1increased the mean Terbutaline FPF from 18.2% to 45.5%. For the volunteer inhalation profiles, a higher FIR tended to be associated with higher PFR, leading to a marked increase in drug FPF due to the combined effect of FIR and PFR.

Conclusion

Drug FPF from either carrier-free or carrier-based formulations is determined by both FIR and PFR. LD is a viable technique to measure the performance of dry powder aerosol formulations at realistic inspiratory flow profiles.

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