Thybo Pia, Hovgaard Lars, Lindeløv Jesper Saederup, Brask Anders, Andersen Sune Klint
Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Pharm Res. 2008 Jul;25(7):1610-20. doi: 10.1007/s11095-008-9565-8. Epub 2008 Apr 11.
The purpose of this study was to investigate the possibility of producing identical powders in pilot and production scale spray drying equipment by matching the droplet size distributions produced by two differently sized atomizers.
Particles were prepared by spray drying solutions of acetaminophen and polyvinylpyrrolidone K-30. The success of the up-scaling was evaluated by comparing the powders in terms of particle size distribution (laser diffraction), crystallinity (XPRD) and morphology (SEM). Furthermore, the influence of process parameters on other product characteristics such as stability and residual volatile content was also evaluated.
The spray drying experiments resulted in spherical, amorphous particles with volumetric median diameters of typically 4-10 microm for pilot scale and 4-30 microm for production scale. The results showed that particles with similar morphology and crystallinity could be produced in the two applied spray dryers. However, scale-up based purely on matching droplet size distributions was not feasible.
The scale-up criterion did not account for the differences between the droplet-drying gas mixing and residence time distribution within the two spray dryers. Therefore, production scale experiments are required in order to obtain similar product characteristics as in pilot scale.
本研究的目的是通过匹配两种不同尺寸雾化器产生的液滴尺寸分布，探讨在中试规模和生产规模的喷雾干燥设备中生产相同粉末的可能性。
通过对乙酰氨基酚和聚乙烯吡咯烷酮K-30的溶液进行喷雾干燥来制备颗粒。通过比较粉末的粒度分布（激光衍射）、结晶度（XPRD）和形态（SEM）来评估放大的成功与否。此外，还评估了工艺参数对其他产品特性（如稳定性和残留挥发物含量）的影响。
喷雾干燥实验得到了球形无定形颗粒，中试规模的体积中径通常为4-10微米，生产规模的为4-30微米。结果表明，在两种应用的喷雾干燥器中可以生产出具有相似形态和结晶度的颗粒。然而，单纯基于匹配液滴尺寸分布进行放大是不可行的。
放大标准没有考虑两种喷雾干燥器内液滴-干燥气体混合和停留时间分布的差异。因此，需要进行生产规模的实验，以获得与中试规模相似的产品特性。
