Maa Y F, Hsu C C
Department of Pharmaceutical Research and Development, Genentech, Inc, 460 Point San Bruno Boulevard, South San Francisco, California 94080, USA.
Biotechnol Bioeng. 1997 Mar 20;53(6):560-6. doi: 10.1002/(SICI)1097-0290(19970320)53:6<560::AID-BIT3>3.0.CO;2-K.
This article documents a feasibility study on coating fine powders with protein solutions using a Würster spray coater (GPCG-1 from Glatt Air Techniques, Ramsey, NJ). Spray coating was based on a fluid-bed process where fluidized microcarriers were coated inside the Würster column and dried in the fluidization chamber. Recombinant human deoxyribonuclease (rhDNase) was used as the model protein. Lactose powders of two different size ranges, 53-125 and 125-250 microm, were used as the model microcarrier. The amount of protein applied was varied to obtain coatings of varying thickness. The extent of rhDNase loading determined experimentally was found to be consistent with the theoretical value and was also confirmed visually by scanning electron microscopy. The coating showed a strong integrity after being subjected to mechanical force. However, the protein suffered serious aggregation during coating, most likely due to the thermal stress of the process. Aggregation was significantly reduced when rhDNase was formulated with calcium ions, consistent with the observation that Ca(2+) thermally stabilized the protein (as determined by scanning microcalorimetry) in aqueous solution. Thus, our study demonstrates that spray coating, particularly when used in conjunction with rational stabilization strategies, is a feasible alternative to other methods of preparing dried pharmaceutical proteins.
本文记录了一项关于使用Würster喷雾包衣机（来自新泽西州拉姆齐市Glatt空气技术公司的GPCG - 1）用蛋白质溶液包衣细粉的可行性研究。喷雾包衣基于流化床工艺，其中流化的微载体在Würster柱内进行包衣，并在流化室内干燥。重组人脱氧核糖核酸酶（rhDNase）用作模型蛋白。两种不同粒径范围（53 - 125微米和125 - 250微米）的乳糖粉末用作模型微载体。改变蛋白质的用量以获得不同厚度的包衣。实验测定的rhDNase负载量与理论值一致，并且通过扫描电子显微镜在视觉上也得到了证实。包衣在受到机械力作用后显示出很强的完整性。然而，在包衣过程中蛋白质发生了严重聚集，很可能是由于该过程的热应力所致。当rhDNase与钙离子一起配制时，聚集显著减少，这与通过扫描量热法测定的Ca(2+)在水溶液中使蛋白质热稳定的观察结果一致。因此，我们的研究表明，喷雾包衣，特别是与合理的稳定化策略结合使用时，是制备干燥药用蛋白质的其他方法的一种可行替代方法。
