Study of the RESS Process for Producing Beclomethasone-17,21-Dipropionate Particles Suitable for Pulmonary Delivery

Abstract

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.

Micronization and characterization of drug substances by RESS with supercritical CO2

“…Rapid expansion of a supercritical solution (RESS) is a promising process for the production of small, uniform and solvent-free powders of solutes with high solubility in SCFs [5][6][7]. The RESS process is advantageous because it can produce fine particles of a wide range of inorganic, organic and polymeric materials and has a low operation temperature and single step processing.…”

“…Some experimental researches [5,6,13] were preformed on the RESS process with supercritical CO 2 preparing fine particles of some drug substances with different solubility. Besides extraction temperature and pressure comprising the major operating parameters of the RESS process, we examined the effect of solutes and some operation parameters including expansion devices on the morphology and size of the fine particles.…”

The Breadth and Intensity of Supercritical Particle Formation Research with an Emphasis on Publication and Patent Disclosures

“…32 Apart from process modifications, several different applications of RESS from encapsulation to deagglomeration and controlled particle deposition were recently reported. Fine microcapsulated red phosphorus particles were fabricated with a new nozzle design, 33 polyacrylonitrile nanofibers were produced, 34 the deagglomeration of the tightly agglomerated multiwalled carbon nanotubes was carried out, 35 porous tablets were loaded with ibuprofen to improve drug dissolution, 36 fine particles of antimalarial drug dihydroartemisinin were prepared, 37 and beclomethasone-17,21-dipropionate, an anti-inflammatory inhaled corticosteroid commonly used to treat asthma, was micronized 38 using the rapid expansion of supercritical solution technique.…”

Supercritical fluid extraction: Recent advances and applications

“…In these processes the supercritical fluid is used to extract the solvent instead of the analyte. In recent years, several reviews [7,179,180,198,199] and original researches [200][201][202][203][204][205][206][207][208][209][210][211][212] have dealt with particle formation processes. Some examples…”