Pharmaceutics and Drug Delivery, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, California 91320, USA.
Pharm Res. 2004 Mar;21(3):507-14. doi: 10.1023/B:PHAM.0000019306.89420.f0.
To evaluate spray-freeze drying and spray drying processes for fabricating micron-sized particles of darbepoetin alfa (NESP, Aranesp) with uniform size distribution and retention of protein integrity, requirements for encapsulation.
Darbepoetin alfa was spray-freeze dried using ultrasonic atomization at 120 kHz and 25 kHz and spray dried at bench-top and pilot scales. Reconstituted powders were evaluated by size exclusion chromatography and UV/VIS spectroscopy. Powder physical properties were also characterized.
Spray-freeze drying resulted in aggregation of darbepoetin alfa. Aggregates (primarily insoluble) formed on drying and/or reconstitution. Particle size distributions were broad (span > or = 3.6) at both nozzle frequencies. Annealing before drying reduced aggregate levels slightly but increased particle size over 5-fold. Spray drying at inlet temperatures up to 135 degrees C (and outlet temperatures up to 95 degrees C) showed little impact on integrity. Integrity at bench-top and pilot scales was identical, with 0.2% dimer and no high molecular weight or insoluble aggregates detected. Particle size was small (< or = 2.3 microm) with uniform distribution (span < or = 1.4) at both process scales.
Under the conditions tested spray drying, conducted at bench-top and pilot scales with commercially available equipment, was superior to spray-freeze drying for the fabrication of darbepoetin alfa particles for encapsulation.
评估喷雾冷冻干燥和喷雾干燥工艺，以制造具有均匀粒径分布和保留蛋白质完整性的达贝泊汀α（NESP，Aranesp）微米级颗粒，这是封装的要求。
达贝泊汀α采用 120 kHz 和 25 kHz 的超声雾化进行喷雾冷冻干燥，并在实验室和中试规模下进行喷雾干燥。通过尺寸排阻色谱法和 UV/VIS 光谱法评估重构粉末。还对粉末物理性质进行了表征。
喷雾冷冻干燥导致达贝泊汀α聚集。在干燥和/或复溶时形成团聚物（主要是不溶性的）。在两种喷嘴频率下，粒径分布都很宽（跨度>或=3.6）。干燥前退火略微降低了聚集水平，但粒径增加了 5 倍以上。在入口温度高达 135°C（出口温度高达 95°C）的条件下进行喷雾干燥，对完整性几乎没有影响。在实验室和中试规模下，完整性相同，仅检测到 0.2%的二聚体，没有高分子量或不溶性聚集物。在两种工艺规模下，粒径均较小（<或=2.3 微米），分布均匀（跨度<或=1.4）。
在测试条件下，商业可用设备在实验室和中试规模下进行的喷雾干燥，优于喷雾冷冻干燥，适用于封装达贝泊汀α颗粒的制备。
