Sterile filtration of a parenteral emulsion

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.