Bouchard Andréanne, Jovanović Natasa, de Boer Anne H, Martín Angel, Jiskoot Wim, Crommelin Daan J A, Hofland Gerard W, Witkamp Geert-Jan
Process Equipment, Delft University of Technology, Leeghwaterstraat 44, Delft, The Netherlands.
Eur J Pharm Biopharm. 2008 Sep;70(1):389-401. doi: 10.1016/j.ejpb.2008.03.020. Epub 2008 Apr 11.
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.
从干燥治疗性蛋白质制剂的生产角度出发，研究了将溶菌酶（作为模型蛋白质）喷雾干燥到超临界二氧化碳中的过程。考察了喷嘴（即并流同轴收敛和收敛-发散喷嘴以及T型混合器撞击式喷嘴）和工艺条件（即流速、压力）对用富含乙醇的超临界二氧化碳干燥水溶液中制备的溶菌酶干燥效果的影响。通过粒径分布、粒径分布宽度和形态来确定所评估的各种参数的影响。根据所选喷嘴的不同，可生产出中位粒径约为1.5微米、约5微米或约25微米的颗粒。通过计算流体动力学对喷嘴进行了基本的比较研究，但这些计算无法描述粒径的差异。流速成比例增加（高达五倍）会导致粒径减小（7至12倍），压力加倍会使粒径适度减小（5%至20%）。用传质模型解释了超临界二氧化碳、乙醇和溶液流的各自作用。由于在富含乙醇的超临界二氧化碳中干燥液滴的膨胀和收缩阶段，流速比的变化会以各种方式对粒径产生轻微影响。
