CIRCULATION OF COMPONENTS DURING MICROFLUIDIZATION AND/OR HOMOGENIZATION OF EMULSIONS
An improved method for the manufacture of an oil-in-water emulsion involves circulation of emulsion components between a first container and a second container via a homogenizer and/or via a microfluidization device. Usefully, all of the emulsion components from the first container are emptied before being returned.
1 - 26 . (canceled)
27 . A method for making a uniform oil-in-water emulsion, the method comprising a step of:
filtering an oil-in-water emulsion with a first hydrophilic polyethersulfone membrane layer having a pore size >0.3 μm and a second hydrophilic polyethersulfone membrane layer having a pore size <0.3 μm, so as to form a uniform oil-in-water emulsion,
wherein the oil-in-water emulsion is characterized in that an average oil droplet size is 500 nm or less, and the number of oil droplets having a size of >1.2 μm is 5×10 10 /ml or less; and,
wherein the uniform oil-in-water emulsion is characterized in that an average oil droplet size is 220 nm or less, and the number of oil droplets having a size of >1.2 μm is 5×10 8 /ml or less.
28 . The method of claim 27 , wherein (a) the first hydrophilic polyethersulfone membrane layer comprises an asymmetric membrane, (b) the second hydrophilic polyethersulfone membrane layer comprises an asymmetric membrane, or combination thereof.
29 . The method of claim 27 , wherein the first hydrophilic polyethersulfone membrane layer and the second hydrophilic polyethersulfone membrane layer are provided as a double-layer filter.
30 . The method of claim 27 , further comprising a step of filtering the uniform oil-in-water emulsion.
31 . The method of claim 27 , wherein the uniform oil-in-water emulsion has an average oil droplet size of between 135-175 nm or between 145-165 nm.
32 . The method of claim 27 , wherein the oil-in-water emulsion has an oil content of between 2-20% (w/v).
33 . The method of claim 27 , wherein the oil-in-water emulsion comprises squalene.
34 . The method of claim 27 , wherein the oil-in-water emulsion comprises a surfactant.
35 . The method of claim 27 , wherein the oil-in-water emulsion comprises squalene, polysorbate 80 and sorbitantrioleate.
36 . The method of claim 27 , wherein the oil-in-water emulsion comprises by volume about 5% squalene, about 0.5% polysorbate 80 and about 0.5% sorbitantrioleate.
37 . A uniform oil-in-water emulsion made by the method according to claim 27 .
38 . The method of claim 27 , further comprising a step of:
adding to the uniform oil-in-water emulsion one or more components to form a pharmaceutical composition comprising the oil-in-water emulsion.
39 . The method of claim 38 , wherein the pharmaceutical composition is sterile.
40 . The method of claim 38 , wherein the pharmaceutical composition comprises an antigen.
41 . The method of claim 38 , wherein the pharmaceutical composition is a vaccine.
42 . A pharmaceutical composition made by the method according to claim 38 .