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Dry Powder and Nebulized Aerosol Inhalation of Pharmaceuticals Delivered to Mice Using a Nose-only Exposure System
Published on: April 6, 2017
The influence of mechanical processing of dry powder inhaler carriers on drug aerosolization performance
Paul M Young1, Hak-Kim Chan, Herbert Chiou
1Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia. py@pharm.usyd.edu.au
Abstract:
The influence of processing on the performance of carrier material used in dry powder inhalers was investigated. alpha-Lactose monohydrate crystals were processed by ball milling for cumulative time durations and their properties evaluated. As expected, milling reduced the median particle diameter while increasing fine particulate (<10 microm) and amorphous levels. Recrystallization of these partially amorphous samples resulted in a reduction in fines, elimination of amorphous material with little change in median diameter. To study the effects of processing on aerosolization performance, blends of lactose monohydrate with a model drug (nedocromil sodium trihydrate), were evaluated using an in vitro multistage liquid impinger (MSLI) model. In general, milling and storage of the carriers at high humidity (prior to blending) had a significant (ANOVA, p < 0.05) effect on the fine particle fractions (FPF; <6.8 microm). These effects were attributed predominantly to the fines content, showing a strong correlation between increased fines and FPF (R(2) = 0.974 and 0.982 for milled and recrystallized samples, respectively). However, this relationship only existed up to 15% fines concentration, after which agglomerate-carrier segregation was observed and FPF decreased significantly. These results suggest that, after processing, high-dose drug formulation performance is dominated by the presence of fines.
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