Ideal controlled
pulmonary drug delivery systems provide sustained
release by retarding lung clearance mechanisms and efficient lung
deposition to maintain therapeutic concentrations over prolonged time.
Here, we use atomic layer deposition (ALD) to simultaneously tailor
the release and aerosolization properties of inhaled drug particles
without the need for lactose carrier. In particular, we deposit uniform
nanoscale oxide ceramic films, such as Al2O3, TiO2, and SiO2, on micronized budesonide
particles, a common active pharmaceutical ingredient for the treatment
of respiratory diseases. In vitro dissolution and ex vivo isolated perfused rat lung tests demonstrate dramatically
slowed release with increasing nanofilm thickness, regardless of the
nature of the material. Ex situ transmission electron
microscopy at various stages during dissolution unravels mostly intact
nanofilms, suggesting that the release mechanism mainly involves the
transport of dissolution media through the ALD films. Furthermore, in vitro aerosolization testing by fast screening impactor
shows a ∼2-fold increase in fine particle fraction (FPF) for
each ALD-coated budesonide formulation after 10 ALD process cycles,
also applying very low patient inspiratory pressures. The higher FPFs
after the ALD process are attributed to the reduction in the interparticle
force arising from the ceramic surfaces, as evidenced by atomic force
microscopy measurements. Finally, cell viability, cytokine release,
and tissue morphology analyses verify a safe and efficacious use of
ALD-coated budesonide particles at the cellular level. Therefore,
surface nanoengineering by ALD is highly promising in providing the
next generation of inhaled formulations with tailored characteristics
of drug release and lung deposition, thereby enhancing controlled
pulmonary delivery opportunities.
Sticking of particles has a tremendous impact on powder-processing industries, especially for hygroscopic amorphous powders. A wide variety of experimental methods has been developed to measure at what combinations of temperature and moisture content material becomes sticky. This review describes, for each method, how socalled stickiness curves are determined. As particle velocity also plays a key role, we classify the methods into static and dynamic stickiness tests. Static stickiness tests have limited particle motion during the conditioning step prior to the measurement. Thus, the obtained information is particularly useful in predicting the long-term behavior of powder during storage or in packaging. Dynamic stickiness tests involve significant particle motion during conditioning and measurement. Stickiness curves strongly depend on particle velocity, and the obtained information is highly relevant to the design and operation of powder production and processing equipment. Virtually all methods determine the onset of stickiness using powder as a starting point. Given the many industrial processes like spray drying that start from a liquid that may become sticky upon drying, future effort should focus on developing test methods that determine the onset of stickiness using a liquid droplet as a starting point.
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