Pharmaceutical TechnologyThe Influence of Mechanical Processing of Dry Powder Inhaler Carriers on Drug Aerosolization Performance
Section snippets
INTRODUCTION
Dry powder inhalers (DPI) are a novel route for drug delivery, with the capability of targeting disease states both locally (in the case of lung diseases such as asthma), and systemically (e.g. in the delivery of proteins and peptides). For effective deposition in the lower airways and deep lung, drug particles with aerodynamic particle sizes of <5 µm are required. However, such systems are highly cohesive due to the high surface area to mass ratio of the particulates. Cohesive systems pose a
Materials
Micronized nedocromil sodium trihydrate (NST) was obtained from Sonafi-Aventis (Cheshire, England). Crystalline α-lactose monohydrate (Lactochem® crystals) was obtained from Borculo Domo (Zwolle, The Netherlands). Water was purified by reverse osmosis (MilliQ, Millipore, Molsheim, France). Analytical grade chloroform and n-octane were obtained from Biolab (Victoria, Australia) and Fluka (Germany), respectively.
Preparation of Lactose Monohydrate Samples
Mechanical treatment of lactose monohydrate samples was achieved by comminution in a
Particle Sizing of Processed Lactose Monohydrate Samples and NST
Particle size analysis of NST gave median diameter of 1.10 µm with 90% particles less than 5.40 µm, suggesting the model drug was suitable for inhalation and DPI studies.
The influence of milling time on the particle size distributions of both freshly milled and recrystallized lactose monohydrate samples was investigated. As expected, the milling process resulted in a significant reduction (ANOVA, p < 0.05) in the median particle diameter with respect to time (Fig. 1). Such observations are
CONCLUSION
Industrial processing of carrier materials used in DPI systems induces changes in the physical properties of the particles. Here, a simple ball milling process was used to produce particles which exhibited a reduced particle size, increased levels of fines and amorphous material. In addition, variation in storage conditions of the processed excipient was also shown to induce changes in fines and amorphous content. When used in a high dose DPI system, significant changes in the FPF were observed
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