Manufacture of surfactant-containing compositions with enhanced stability
Improved methods for the manufacture of pharmaceutical compositions comprising at least one surfactant, involving prefiltration of the surfactant prior to formulation into final products.
1. A process for preparing an oil-in-water emulsion comprising steps of:
(a) purifying polysorbate 80 by filtering polysorbate 80 through a filter having a pore size between 5-50 μm; and
(b) forming the oil-in-water emulsion by either:
i) combining the purified polysorbate 80 with an aqueous component and adding an oil component; or
ii) combining the purified polysorbate 80 with an oil component and adding an aqueous component.
2. The process of claim 1 , wherein the filter is a polypropylene filter.
3. The process of claim 1 , wherein the oil-in-water emulsion formed in step (b) is homogenized.
4. The process of claim 1 , wherein the oil-in-water emulsion formed in step (b) is microfluidized.
5. The process of claim 3 , wherein step (b) further comprises sterile filtration of the homogenized oil-in-water emulsion.
6. The process of claim 1 , wherein the oil-in-water emulsion is a vaccine adjuvant including squalene.
7. The process of claim 6 , wherein the oil-in-water emulsion comprises squalene, the polysorbate 80, and sorbitan trioleate.
8. The process of claim 1 , wherein the oil-in-water emulsion has less than 0.85 ppm acetaldehyde.
9. The process of claim 1 , wherein the oil-in-water emulsion comprises squalene and the emulsion has less than 661 picograms of polychlorinated biphenyls per gram of squalene (toxic equivalent TEQ).
10. A method for preparing (i) a vaccine composition, comprising preparing an oil-in-water emulsion according claim 1 and combining the emulsion with an antigen, or (ii) a vaccine kit comprising preparing an oil-in-water emulsion according to claim 1 and packaging the emulsion into a kit as a kit component together with an antigen component.
11. The method of claim 10 , wherein the antigen is an influenza virus antigen.
12. The process of claim 4 , wherein step (b) comprises sterile filtration of the microfluidized emulsion.
13. The method of claim 11 , wherein the combination of the emulsion and the antigen forms a vaccine composition and wherein the vaccine composition includes about 15 μg, about 10 μg, about 7.5 μg, about 5 μg, about 3.8 μg, about 1.9 μg, or about 1.5 μg of hemagglutinin per influenza virus strain.
14. A process for preparing an oil-in-water emulsion comprising steps of:
(a) purifying a composition comprising polysorbate 80 and an aqueous component by filtering the composition through a filter having a pore size between 5-50 μm; and
(b) forming the oil-in-water emulsion by combining the purified composition comprising polysorbate 80 and the aqueous component with an oil component.