Supercritical anti-solvent precipitation of ethyl cellulose

Supercritical anti-solvent (SAS) process is considered to be a clean technology suitable for particle design. It is generally used in order to micronize compounds of interest under mild operating conditions of temperature and with very low residual solvent traces in the end-product. By varying the process parameters, the properties of the produced powders can be adjusted with defined size (generally micron or nanometer sized particles), morphology and a narrow particle size distribution. There is currently a growing interest for the elaboration of controlled delivery systems. For this purpose, the SAS process can also be applied in order to co-precipitate molecules of interest with biocompatible and/or biodegradable polymers. An experimental study dealing with supercritical anti-solvent (SAS) precipitation has been carried out in order to micronize a biocompatible polymer, ethyl cellulose, widely used as a drug carrier in controlled delivery systems for oral administration. Supercritical carbon dioxide was used as anti-solvent for the polymer and ethyl acetate (EtAc), generally recognized as safe (GRAS) by the FDA (Food and Drug Administration) as solvent. The influence of the variation of the main operating parameters upon the characteristics of the micronized polymer was evaluated. In particular, the temperature (308, 318 and 333 K), the polymer concentration (1,3 and 4 wt%), the EtAc/CO2 molar ratio (5 and 8 mol%) and the capillary tube diameter (127 and 254 mu m) while pressure was kept constant and equal to 10 MPa. Using a low organic solution concentration of 1 wt% and at a temperature of 308 K, ethyl cellulose was successfully micronized in submicron particles with a mean size of 300 nm. However, increasing the temperature or the polymer concentration in the organic solution favored the particle coalescence and even led to fiber formation. (C) 2015 Elsevier B.V. All rights reserved.