Effect of the spraying conditions and nozzle design on the shape and size distribution of particles obtained with supercritical fluid drying

Publication Type:

Journal Article


European Journal of Pharmaceutics and Biopharmaceutics, Volume 70, Number 1, pp. 389-401 (2008)



DOI Name (links to online publication)



atomisation; lysozyme; particle size distribution; mass transfer; computational fluid dynamics; carbon-dioxide; liquid-equilibrium; elevated pressures; aqueous-solutions; antisolvent; water; precipitation; morphology; mixtures; crystallization


In the perspective of production of dry therapeutic protein formulations, spray drying of lysozyme (as a model protein) into Supercritical carbon dioxide was studied. The effects of the nozzle (i.e., co-current coaxial converging and converging-diverging, and T-mixer impinging) and process conditions (i.e., flow rates, pressure) on the drying of the lysozyme prepared in aqueous solution dried with supercritical carbon dioxide enriched with ethanol were investigated. The particle size distribution, width of particle size distribution and morphology were used to determine the effect of the various parameters assessed. Particles with a median size of similar to 1.5, similar to 5 or similar to 25 mu m were produced depending of the nozzle selected. A basic comparative study of the nozzle was done by computational fluid dynamics, but the differences in particle size could not be depicted by these computations. The proportional increase of the flow rates (tip to fivefold) caused a decrease in particle size (7- to 12-fold), and doubling the pressure caused a moderate decrease of the size (5-20%). The individual effect of the supercritical carbon dioxide, ethanol and solution streams was explained with a mass transfer model. Changing the ratio between flow rates slightly affected the particle size in various ways because of the swelling and shrinking stages of the drying droplet in supercritical carbon dioxide enriched with ethanol. (C) 2008 Elsevier B.V. All rights reserved.