Manufacture of Oil-in-Water Emulsion Adjuvants.

Emulsion adjuvants for human vaccines have evolved gradually over the last century. Current formulations are the result of many refinements to their composition and manufacturing, as well as optimization for safety and efficacy. Squalene has emerged as being particularly suitable for the manufacturing of safe oil-in-water (O/W) adjuvants for parenteral applications due to its biocompatibility and ability to be metabolized. Emulsion particle size has been identified as an important parameter affecting the pharmaceutical performance of O/W emulsion adjuvants. Submicronic emulsions with sizes in the 80-200 nm range are preferred for potency, manufacturing consistency, and stability reasons. Two manufacturing processes, high pressure homogenization (HPH or microfluidization) and a phase inversion temperature method (PIT), are described to yield such fine and long-term stable emulsion adjuvants.