Powder Rheometry Research Articles

Understanding the influence of powder flowability, fluidization and de-agglomeration characteristics on the aerosolization of pharmaceutical model powders

The aim of this study was to investigate the influence of the intrinsic inter-particulate cohesion of model pharmaceutical powders on their aerosolization from a dry powder inhaler. Two cohesive poly-disperse lactose powders with median particle sizes of around 4 and 20 μm were examined. The results showed that after dry coating with magnesium stearate, their flowability, fluidization and de-agglomeration behaviours could be substantially improved, as indicated by powder rheometry, shear testing and laser diffraction aerosol testing. This was achieved by reducing their cohesiveness via surface modification. In contrast to some previous reports, this study demonstrated how powder aerosolization may be improved more significantly and consistently (for widely varying air flow rates) by substantially reducing their inter-particulate cohesive forces. This study contributes to the understanding of the relationship between intrinsic cohesive nature and bulk properties such as flowability, fluidization and de-agglomeration and its impact on their aerosolization, which is fundamental and critical in the optimal design of dry powder inhaler formulations. The intensive mechanical dry coating technique also demonstrated a promising potential to improve aerosolization efficiency of fine cohesive model powders.

Characterisation and functionality of inhalation anhydrous lactose

The relationships between the physicochemical properties and functionality in dry powder inhaler (DPI) performance was investigated for inhalation grade anhydrous lactose and compared to monohydrate grades. The excipients were characterised using a range of techniques including particle size analysis, moisture sorption and powder rheometry. The inhalation anhydrous lactose grades were readily characterisable. The aerosolisation performance of capsule based DPI formulations containing budesonide (200 μg) and different grades of lactose evaluated using inertial impaction measurements produced fine particle doses of budesonide ranging from 24 to 49 μg. There were no apparent relationships between aerosolisation performance and excipient characteristics, such as particle size and powder density. However, formulations containing lactose grades which exhibit higher powder fluidisation energy values resulted in higher fine particle doses of budesonide.

Effect of host particle size on the modification of powder flow behaviours for lactose monohydrate following dry coating

Our previous work demonstrated that the powder flowability of a cohesive lactose sample can be improved substantially using a dry coating technique. Our study reported here aims to investigate the influence of host particle size on the modification of powder flowability following dry coating process. Four commercial lactose monohydrate powders with different particle sizes were coated by an intensive mechanical process or mixed using a conventional tumbling process, both with magnesium stearate. All four untreated lactose samples showed a relatively poor powder flow. After dry coating, poured and tapped densities of all the lactose samples increased, while Carr indices and Hausner ratios decreased substantially. The angle of repose values were reduced to a notable extent only for particles with a median size larger than about 7 μm after dry coating. Both specific energy (SE) and cohesion values of lactose samples, measured by a powder rheometer system, decreased substantially after coating. In contrast, no apparent changes in powder flow were evident for conventionally mixed batches, except that in the dynamic powder rheometry measurement, a relatively small change in SE was observed. This study demonstrated that for the finer particles examined, cohesive forces were more influential in the powder bed after the surface treatment and resulted in a relatively poor flow. However, for the larger powders studied, the cohesive inter-particle forces could be overcome after this dry coating, whereby satisfactory flow could be obtained. This study indicated that the host particle size was a critical factor in influencing the modification of cohesive powder flowability.