Effect of the spraying conditions and nozzle design on the shape and size distribution of particles obtained with supercritical fluid drying.
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 approximately 1.5, approximately 5 or approximately 25 microns 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 (up 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.
Bouchard
Andréanne
A
Process Equipment, Delft University of Technology, Leeghwaterstraat 44, Delft, The Netherlands. a.m.j.l.bouchard@tudelft.nl
Jovanović
Natasa
N
de Boer
Anne H
AH
Martín
Angel
A
Jiskoot
Wim
W
Crommelin
Daan J A
DJ
Hofland
Gerard W
GW
Witkamp
Geert-Jan
GJ
D002245:Carbon Dioxide / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D003890:Desiccation / Q000295:instrumentation; D004867:Equipment Design; D000431:Ethanol / Q000737:chemistry; D008956:Models, Chemical; D009113:Muramidase / Q000737:chemistry*; D010316:Particle Size; D011208:Powders; D012212:Rheology; D012997:Solvents / Q000737:chemistry*; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods
D011208:Powders; D012997:Solvents; D002245:Carbon Dioxide; D000431:Ethanol; D009113:Muramidase