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 emulsion comprising steps of:
(a) purifying a surfactant by filtering said surfactant through a filter having a pore size between 5-50 μm; and
(b) forming the emulsion by:
i. combining the purified surfactant with an aqueous component and adding an oil component; or
ii. combining the purified surfactant with an oil component and adding an aqueous component.
2. The process of claim 1 , wherein the surfactant is a polymeric surfactant.
3. The process of claim 2 , wherein the polymeric surfactant is polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, t-octylphenoxypolyethoxyethanol, (octylphenoxy)polyethoxyethanol, poloxamers, or polyoxyethylene alkyl ether.
4. The process of claim 1 , wherein the surfactant is polysorbate 80 and step (a) comprises: filtering non-aqueous polysorbate 80 through a polypropylene filter having a pore size between 10-40 μm.
5. The process of claim 1 , wherein the purified surfactant is combined with an aqueous material between steps (a) and (b).
6. The process of claim 1 , wherein the emulsion is an oil-in-water emulsion.
7. The process of claim 1 , wherein the emulsion is a water-in-oil emulsion.
8. The process of claim 1 , wherein the emulsion is a water-in-oil-in-water emulsion.
9. The process of claim 1 , wherein the oil component comprises squalene.
10. The process of claim 2 , wherein the oil component comprises squalene.
11. The process of claim 1 , wherein step (b) comprises homogenization to form a homogenized emulsion.
12. The process of claim 11 , wherein step (b) comprises sterile filtration of the homogenized or microfluidized emulsion.
13. The process of claim 1 , wherein the purified surfactant is a bulk preparation of purified surfactant having a volume of at least 50 litres.
14. The process of claim 1 , wherein the emulsion is a vaccine adjuvant.
15. The process of claim 1 , wherein the emulsion has less than 0.85 ppm acetaldehyde.
16. The process of claim 1 , wherein the emulsion comprises squalene and the emulsion has less than 661 picograms of polychlorinated biphenyls per gram of squalene (toxic equivalent TEQ).
17. A method for preparing a vaccine composition, comprising preparing an emulsion according to claim 1 and combining the emulsion with an antigen.
18. A method for preparing a vaccine kit comprising preparing an emulsion according to claim 1 and packaging the emulsion into a kit as a kit component together with an antigen component.
19. The method of claim 17 , wherein the antigen is an influenza virus antigen.
20. The method of claim 19 , wherein the vaccine composition includes about 15 about 10 about 7.5 about 5 about 3.8 about 1.9 or about 1.5 μg of hemagglutinin per influenza virus strain.
21. The method of claim 18 , wherein the antigen is an influenza virus antigen.
22. The method of claim 21 , 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.
23. A method for preparing a pharmaceutical composition comprising preparing an emulsion according to claim 2 and formulating a pharmaceutical composition comprising the emulsion.