Arranging interaction and back pressure chambers for microfluidization
An improved method for the manufacture of an oil-in-water emulsion comprises using a microfluidization device whose interaction chamber comprises a plurality of Z-type channels upstream of a back pressure chamber.
1. A method for the manufacture of an oil-in-water emulsion comprising the step of passing a first emulsion having a first average oil droplet size through a microfluidization device to form a second emulsion having a second average oil droplet size which is less than the first average oil droplet size,
wherein the microfluidization device comprises an interaction chamber;
wherein the pressure of the first emulsion components at the entrance to the interaction chamber is substantially constant for at least 85% of the time during which the first emulsion is fed into the microfluidizer; and
wherein the number of oil droplets having a size of >1.2 μm in the second emulsion is 5×10 10 /ml or less.
2. The method of claim 1 , wherein the microfluidization device comprises two intensifier pumps.
3. The method of claim 1 , further comprising the step of filtering the second emulsion.
4. The method of claim 1 , further comprising the step of forming the first emulsion using a homogenizer.
5. The method of claim 1 , wherein the first average oil droplet size is 5000 nm or less.
6. The method of claim 1 , wherein the number of oil droplets having a size of >1.2 μm in the first emulsion is 5×10 11 /ml or less.
7. The method of claim 1 , wherein the second average oil droplet size is 500 nm or less.
8. A method for preparing a vaccine composition, comprising preparing an emulsion according to the method of claim 1 and combining the emulsion with an antigen.
9. A method for preparing a vaccine kit comprising preparing an emulsion according to the method of claim 1 and packaging the emulsion into a kit as a kit component together with an antigen component.
10. The method of claim 9 , wherein the kit components are in separate vials.
11. The method of claim 10 , wherein the vials are made from borosilicate glass.
12. The method of claim 9 , wherein the adjuvant is a bulk adjuvant and the method comprises extracting unit doses from the bulk adjuvant for packaging as kit components.
13. The method of claim 8 , wherein the antigen is an influenza virus antigen.
14. The method of claim 8 , wherein the combination of the emulsion and the antigen forms a vaccine composition and wherein the vaccine composition comprises about 1.5 μg to about 15 μg of hemagglutinin per influenza virus strain.
15. The method of claim 13 , wherein the combination of the emulsion and the antigen forms a vaccine composition and wherein the vaccine composition further comprises a preservative which is thiomersal or 2 phenoxyethanol.
16. The method of claim 14 , wherein the combination of the emulsion and the antigen forms a vaccine composition and wherein the vaccine composition further comprises a preservative which is thiomersal or 2 phenoxyethanol.