Study of the RESS Process for Producing Beclomethasone-17,21-Dipropionate Particles Suitable for Pulmonary Delivery
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The purpose of this research was to micronize beclomethasone-17,21-dipropionate (BDP), an anti-inflammatory inhaled corticosteroid commonly used to treat asthma, using the rapid expansion of supercritical solution (RESS) technique. The RESS technique was chosen for its ability to produce both micron particles of high purity for inhalation, and submicron/nano particles as a powder handling aid for use in next generation dry powder inhalers (DPIs). Particle formation experiments were carried out with a capillary RESS system to determine the effect of experimental conditions on the particle size distribution (PSD). The results indicated that the RESS process conditions strongly influenced the particle size and morphology; with the BDP mean particle size decreasing to sub-micron and nanometer dimensions. An increase in the following parameters, i.e. nozzle diameter, BDP mol fraction, system pressure, and system temperature; led to larger particle sizes. Aerodynamic diameters were estimated from the SEM data using three separate relations, which showed that the RESS technique is promising to produce particles suitable for pulmonary delivery.
Key wordsasthma beclomethasone dipropionate crystallization micronization supercritical fluid processing
The authors thank Dr. J. P. Mitchell of Trudell Medical International for the fruitful discussions during this work, Dr. Michiel Van Oort of GlaxoSmithKline, and Mr. Brad Kobe of Surface Science Western for use of the Scanning Electron Microscope. This work was financially supported by the Canadian Natural Science and Engineering Research Council (NSERC) and by the University of Western Ontario Academic Development Fund.
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