Structural influence of cohesive mixtures of salbutamol sulphate and lactose on aerosolisation and de-agglomeration behaviour under dynamic conditions.
OBJECTIVE
The purpose of this study was to understand the behaviour of cohesive powder mixtures of salbutamol sulphate (SS) and micronized lactose (LH300) at ratios of SS:LH300 of 1:1, 1:2, 1:4 and 1:8 under varying air flow conditions.


METHODS
Aerosolisation of particles less than 5.4μm at air flow rates from 30 to 180 l min(-1) was investigated by determining particle size distributions of the aerosolised particles using laser diffraction and fine particle fractions of SS using the twin stage impinger modified for different air flow rates using a Rotahaler(®). The de-agglomeration data were best fitted by a 3-parameter sigmoidal equation using non-linear least squares regression and characterised by the estimated parameters.


RESULTS
De-agglomeration air flow rate profiles showed that SS:LH300 mixtures with increased lactose content (1:4 and 1:8) improved powder aerosolisation, but lactose had negligible effect on SS aerosolisation at the higher and lower limits of air flow rates studied. De-agglomeration flow rate profiles of SS-LH300 mixtures with increased lactose content (1:4 and 1:8) were greater than theoretically expected based on weighted individual SS and LH300 profiles. This indicated that interactions between the cohesive components led to enhanced de-agglomeration. The composition of the aerosol plume changed with air flow rate.


CONCLUSIONS
This approach to characterising aerosolisation behaviour has significant applications in understanding powder structures and in formulation design for optimal aerosolisation properties.
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Srinivas Ravindra Babu
SR
Behara
Paul
P
Kippax
Michelle P
MP
McIntosh
David A V
DA
Morton
Ian
I
Larson
Peter
P
Stewart
D000336:Aerosols; D000420:Albuterol / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D007785:Lactose / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D010316:Particle Size
D000336:Aerosols; D007785:Lactose; D000420:Albuterol