Objectives: To evaluate physicochemical properties of
two micronized drugs, salbutamol sulfate (SS) and beclomethasone
dipropionate (BDP) prepared as dry powder inhalation physical blends. Methods:
Five different blends of SS:BDP ratios of 0:100, 25:75, 50:50, 75:25,
and 100:0 (w/w) were prepared. Aerosolization performance was evaluated
using a multistage impinger and a Rotahaler® device. Results: The median SS particle diameter was larger than BDP (4.33 ± 0.37 µm compared to 2.99 ± 0.15 µm,
respectively). The SS appeared to have a ribbon-like morphology, while
BDP particles had plate-like shape with higher cohesion than SS. This
was reflected in the aerosolization performance of the two drugs alone,
where SS had a significantly higher fine particle fraction (FPF) than
BDP (12.3%, 3.1% and 2.9%, 0.2%, respectively). The study of cohesion
versus adhesion for a series of SS and BDP probes on SS and BDP
substrates suggested both to be moderately adhesive, verified using
scanning Raman microscopy, where a physical association between the two
was observed. A plot of loaded versus emitted dose indicated that powder
bed fluidization was significantly different when the drugs were tested
individually. Furthermore, the FPF of the two drugs from the binary
blends, at all three ratios, were similar. Conclusions: Such
observations indicate that when these two drugs are formulated as a
binary system, the resulting powder structure is altered and the
aerosolization performance of each drug is not reflective of the
individual drug performance. Such factors could have important
implications and should be considered when developing combination dry
powder inhalation systems.
