Influenza vaccine powder formulation development: Spray-freeze-drying and stability evaluation
Influenza vaccine powder formulation development: Spray-freeze-drying and stability evaluation
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DOI：
10.1002/jps.20104
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发表时间：
2004-07-01
影响因子：
3.8
通讯作者：
Chen, DX
中科院分区：
文献类型：
--
作者：
Maa, YF;Ameri, M;Chen, DX
本研究的目的是开发一种适合于表皮粉末免疫的流感疫苗干粉制剂的喷雾冷冻干燥(SFD)工艺。在预配制两种流感疫苗后，SFD制备了它们的干粉制剂。通过粒度分析、敲击密度测量、扫描电子显微镜、光学显微镜和水分含量分析来确定粉末的性质和物理稳定性。用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳法、单向免疫扩散法和小鼠体内免疫原性试验测定疫苗抗原的化学和生化稳定性。我们证明，SFD可以产生高密度颗粒--这是有效渗透皮肤的关键参数。从稳定性的角度来看，SFD造成的压力是轻微的，因为干粉中的抗原保持了它的稳定性、效力和免疫原性。在筛选的几种配方中，我们注意到配方组成对粉末的长期物理和生化稳定性具有重要作用。尤其是一种含有亚单位疫苗(45杯抗原，1毫克粉末)和海藻糖、甘露醇和葡聚糖三级混合物的配方，总体表现良好。稳定性，包括暴露在高湿度环境中后可接受的生化稳定性。毕竟，我们不仅证明了SFD适合于制备用于表皮粉末免疫的粉末，而且还开发了一种系统的配方开发策略，使流感疫苗干粉配方得以优化。更重要的是，这项研究导致了一种配方系统的选择，该配方系统已在人类临床研究中成功测试。(C)2004年Wiley-Liss，Inc.和美国药剂师协会。
The purpose of this study was to develop a spray-freeze-drying (SFD) process for preparing an influenza vaccine dry powder formulation suitable for epidermal powder immunization. After preformulation of two types of flu vaccines, their dry-powder formulations were prepared by SFD. Powder properties and physical stability were determined using particle size analysis, tap density measurement, scanning electron microscopy, optical microscopy, and moisture content analysis. Chemical and biochemical stability of vaccine antigens was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, single radial immunodiffusion assay, and in vivo immunogenicity in a mouse model. We demonstrated that SFD could produce high-density particles-a critical parameter for effective skin penetration. From the stability perspective, the stress posed by SFD was mild because the antigen in the dry powder retained its stability, potency, and immunogenicity. Among several formulations screened, we noted that formulation composition has a significant role in the powder's long-term physical and biochemical stability. One formulation, in particular, containing sub-unit vaccine (45 mug of antigen in I mg of powder) with a tertiary mixture of trehalose, mannitol, and dextran, exhibited excellent overall. stability, including acceptable biochemical stability after being exposed to a highly humid environment. After all, we have not only demonstrated the suitability of SFD to prepare powders for epidermal powder immunization but also developed a systematic formulation development strategy that allowed the optimization of an influenza vaccine dry powder formulation. More important, this study led to the selection of a formulation system that had been successfully tested in a human clinical study. (C) 2004 Wiley-Liss, Inc. and the American Pharmacists Association.