Production of Nano Size Particles of Cyclodextrins from Aqueous Solution by the Dense

Gas Technique
R. Mammucari1, F. Dehghani1, H. L. Regtop2, and N. R. Foster1
1
The University of New South Wales, 2Eiffel Technologies Limited
Purpose. Cyclodextrins (CDs) are cyclic non-reducing, oligosaccharides with a cavity that is hydrophobic relative to an
aqueous environment. The characteristic of interest with cyclodextrins is their ability to form non-covalent inclusion
complexes. These inclusion complexes can be used to increase solubility and dissolution rate, decrease volatility, alter release
rates, modify local irritation and increase the stability of pharmaceuticals. The aim of this study was to produce nano-
particles of cyclodextrins to be used for delivery of drugs by transdermal, nasal, and pulmonary delivery. A micronisation
process was used to avoid using hazardous organic solvents due to low solubility of cyclodextrins in such solvents and to
minimise the presence of residual solvent in the final product.

Methods. The Aerosol Solvent Extraction System (ASES) was developed to utilise the unique properties of supercritical
fluids such as carbon dioxide to produce nano-sized particles with a narrow particle size distribution and minimal residual
solvent. The ASES process was employed to precipitate β-cyclodextrin (β−CD) and hydroxy propyl β-cyclodextrin (HP-
βCD) from an aqueous solutions using carbon dioxide at 37°C and 160 bar modified with 20 mol% ethanol as an anti-
solvent. The effect of concentration of solution, flow rate and nozzle size on the CDs precipitation was examined. The
characteristics of the precipitates were determined by Scanning Electron Microscopy, and Malvern Master Sizer. The aerosol
performance of the powder was measured by the Anderson cascade impactor.

Results. Both β−CD and HP-β−CD were precipitated as discrete spheres with a particle size less than 400 nm. The
characteristics of the CDs precipitated by the ASES from aqueous solution were not significantly influenced by the operating
parameters. The recovery of the product for the β-CD was more than HP-β-CD due to the higher solubility of latter in water.
In vitro analysis was performed to study the aerosol performance of the CDs processed by the ASES technique. The fine
particle mass (< 5 µm) was at least 70%.

Conclusions. The results of this study demonstrate that the ASES technique was an efficient method for production of nano-
particles of HP-β-CD and β-CD CDs from aqueous solution. No toxic organic solvent remained in the final product. The
ASES technique can be used for the production of drug-CD complex suitable for inhalation or transdermal delivery.