PowderJect Vaccines, Inc., 585 Science Drive, Madison, Wisconsin 53711, USA.
Pharm Res. 2004 Mar;21(3):515-23. doi: 10.1023/B:PHAM.0000019307.27058.a1.
Fluid-bed spray-coating process is widely used to prepare non-protein pharmaceutical solid dosage forms using macro-size seed particles (200-1000 microm) at kilogram batch sizes. In this study we developed a small-scale fluid-bed spray-coating process (20 g) to produce micro-sized vaccine powder formulations (40-60 microm) for epidermal powder immunization (EPI) METHODS: A bench-top spray coater was used to spray two vaccines, diphtheria toxoid (dT) and alum-adsorbed hepatitis-B surface antigen (Alum-HBsAg), onto crystalline lactose particles of 40-60 microm in diameter. Particle properties such as particle size, surface morphology, and degree of particle agglomeration were determined. Protein stability was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The immunogenicity of the vaccine was evaluated in vivo by needle injection and epidermal powder immunization (EPI) of mice or guinea pigs.
Coating feasibility was demonstrated for both vaccine formulations containing different excipients. However, the nature of the vaccine antigen appeared to affect coating feasibility in terms of particle agglomeration considerably. Delivery of spray-coated dT and alum-HBsAg through EPI to mice and guinea pigs, respectively, generated significant antibody responses, at a level comparable to liquid formulation delivered subcutaneously through needle/syringe injection.
The new spray-coating process represents an important technical advance and may provide a useful tool for developing high-valued biopharmaceutical powder formulations for novel applications. The strong in vivo performance of the coated dT and alum-HBsAg powders by EPI further demonstrated that spray-coating is a viable dry powder formulation process and the skin's epidermal layer presents an efficient vaccine delivery route.
流化床喷雾包衣工艺广泛用于使用公斤批量的大尺寸种子颗粒（200-1000 微米）制备非蛋白质药物固体制剂。在这项研究中，我们开发了一种小规模流化床喷雾包衣工艺（20 克），用于生产用于表皮粉末免疫（EPI）的微尺寸疫苗粉末配方（40-60 微米）。方法：使用台式喷雾包衣机将两种疫苗，白喉类毒素（dT）和吸附在明矾上的乙型肝炎表面抗原（Alum-HBsAg），喷涂到直径为 40-60 微米的结晶乳糖颗粒上。测定了颗粒性质，如颗粒大小、表面形态和颗粒团聚程度。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析蛋白质稳定性。通过皮下注射和表皮粉末免疫（EPI）对小鼠或豚鼠进行体内评估疫苗的免疫原性。结果：两种含有不同赋形剂的疫苗配方的包衣可行性均得到证明。然而，疫苗抗原的性质似乎在颗粒团聚方面极大地影响了包衣的可行性。通过 EPI 向小鼠和豚鼠分别递送达喷雾包衣的 dT 和 Alum-HBsAg，分别产生了与皮下通过针/注射器注射的液体制剂相当的显著抗体反应。结论：新的喷雾包衣工艺代表了一项重要的技术进步，可为新型应用开发高价值的生物制药粉末配方提供有用的工具。通过 EPI 对包衣的 dT 和 Alum-HBsAg 粉末的强烈体内性能进一步证明了喷雾包衣是一种可行的干粉制剂工艺，皮肤的表皮层呈现出有效的疫苗递送途径。
