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


METHODS
Carrier-based formulations containing 1.5% w/w micronized salbutamol base blended with the 63-90 microm 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(-1) s(-1) although 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 (R (2) = 0.95, p < 0.01, ANOVA). For the Bricanyl Turbohaler, increasing FIR from 120 to 600 l min(-1) s(-1) for a constant peak flow rate (PFR) of 60 l min(-1) increased 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.


CONCLUSIONS
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.
Martin
Gary P
GP
Pharmaceutical Science Research Division, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. gary.martin@kcl.ac.uk
Marriott
Christopher
C
Zeng
Xian-Ming
XM
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D004337:Drug Carriers; D006801:Humans; D007785:Lactose; D007834:Lasers; D008320:Maltose; D008953:Models, Anatomic; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders; D013012:Sorbitol; D013726:Terbutaline / Q000008:administration & dosage
D000318:Adrenergic beta-Agonists; D000336:Aerosols; D018927:Anti-Asthmatic Agents; D004337:Drug Carriers; D011208:Powders; D013012:Sorbitol; D008320:Maltose; D007785:Lactose; D013726:Terbutaline; D000420:Albuterol