Lidgate D M, Trattner T, Shultz R M, Maskiewicz R
Institute of Pharmaceutical Science, Syntex Research, Palo Alto, California 94304.
Pharm Res. 1992 Jul;9(7):860-3. doi: 10.1023/a:1015836512890.
The Syntex adjuvant formulation (SAF) containing [thr1]-muramyldipeptide in an oil-in-water emulsion has proven to be an effective adjuvant eliciting both cell-mediated and humoral immune response. As a parenteral emulsion, sterility of the final product was a concern, and various methods of achieving sterility were considered. For emulsions, most conventional sterilization methods are not viable, requiring the more cumbersome technique of sterilizing individual components and assembling/manufacturing under sterile conditions. Emulsion vehicles were manufactured with various models in the Microfluidizer M110 series. All equipment examined was capable of reducing the average dispersed oil droplet size to approximately 160 nm, with varying size ranges. Operating at an internal equipment pressure of greater than 16,000 psi, with at least five cycles through the interaction chamber, the resulting emulsion had a narrow droplet size range distribution, with the largest droplets being small enough to enable sterile filtration. Under specific-manufacturing conditions, the adjuvant emulsion becomes easily filtered through a 0.22-micron cartridge filter, thus yielding a sterile end product. This is the first published example of emulsion sterilization being achieved by terminal filtration.
含有[苏氨酸1]-胞壁酰二肽的水包油乳剂形式的Syntex佐剂配方（SAF）已被证明是一种有效的佐剂，可引发细胞介导的和体液免疫反应。作为一种肠胃外乳剂，最终产品的无菌性是一个关注点，人们考虑了实现无菌的各种方法。对于乳剂而言，大多数传统的灭菌方法不可行，需要采用更为繁琐的技术，即对各个成分进行灭菌，并在无菌条件下进行组装/制造。乳剂载体采用微流化器M110系列中的各种型号制造。所检查的所有设备都能够将平均分散油滴尺寸减小到约160纳米，尺寸范围各不相同。在设备内部压力大于16,000磅力/平方英寸的条件下运行，且至少通过相互作用腔循环五次，所得到的乳剂具有窄的液滴尺寸范围分布，最大的液滴小到足以进行无菌过滤。在特定的制造条件下，佐剂乳剂很容易通过0.22微米的筒式过滤器进行过滤，从而得到无菌的最终产品。这是通过终端过滤实现乳剂灭菌的首个公开实例。
