Maa Y F, Nguyen P A, Sweeney T, Shire S J, Hsu C C
Genentech, Inc., South San Francisco, California 94080, USA.
Pharm Res. 1999 Feb;16(2):249-54. doi: 10.1023/a:1018828425184.
To develop a new technique, spray freeze drying, for preparing protein aerosol powders. Also, to compare the spray freeze-dried powders with spray-dried powders in terms of physical properties and aerosol performance.
Protein powders were characterized using particle size analysis, thermogravimetric analysis, scanning electron microscopy, X-ray powder diffractometry, and specific surface area measurement. Aerosol performance of the powders was evaluated after blending with lactose carriers using a multi-stage liquid impinger or an Anderson cascade impactor. Two recombinant therapeutic proteins currently used for treating respiratory tract-related diseases, deoxyribonuclase (rhDNase) and anti-IgE monoclonal antibody (anti-IgE MAb), were employed and formulated with different carbohydrate excipients.
Through the same atomization but the different drying process, spray drying (SD) produced small (approximately 3 microns), dense particles, but SFD resulted in large (approximately 8-10 microns), porous particles. The fine particle fraction (FPF) of the spray freeze-dried powder was significantly better than that of the spray-dried powder, attributed to better aerodynamic properties. Powders collected from different stages of the cascade impactor were characterized, which confirmed the concept of aerodynamic particle size. Protein formulation played a major role in affecting the powder's aerosol performance, especially for the carbohydrate excipient of a high crystallization tendency.
Spray freeze drying, as opposed to spray drying, produced protein particles with light and porous characteristics, which offered powders with superior aerosol performance due to favorable aerodynamic properties.
开发一种用于制备蛋白质气溶胶粉末的新技术——喷雾冷冻干燥。同时，在物理性质和气溶胶性能方面比较喷雾冷冻干燥粉末与喷雾干燥粉末。
使用粒度分析、热重分析、扫描电子显微镜、X射线粉末衍射和比表面积测量对蛋白质粉末进行表征。使用多级液体冲击器或安德森级联冲击器将粉末与乳糖载体混合后评估其气溶胶性能。采用两种目前用于治疗呼吸道相关疾病的重组治疗性蛋白质，即脱氧核糖核酸酶（rhDNase）和抗IgE单克隆抗体（抗IgE MAb），并与不同的碳水化合物辅料进行配方。
通过相同的雾化但不同的干燥过程，喷雾干燥（SD）产生小的（约3微米）、致密的颗粒，而喷雾冷冻干燥产生大的（约8 - 10微米）、多孔的颗粒。喷雾冷冻干燥粉末的细颗粒分数（FPF）明显优于喷雾干燥粉末，这归因于更好的空气动力学性质。对从级联冲击器不同阶段收集的粉末进行了表征，证实了空气动力学粒径的概念。蛋白质配方在影响粉末的气溶胶性能方面起主要作用，特别是对于具有高结晶倾向的碳水化合物辅料。
与喷雾干燥相反，喷雾冷冻干燥产生具有轻质和多孔特性的蛋白质颗粒，由于有利的空气动力学性质，这些颗粒提供了具有优异气溶胶性能的粉末。
