Aqueous nebulization composition
Compositions and methods for making and using stable, homogeneous budesonide compositions are disclosed.
1. A stable, homogeneous budesonide composition comprising:
i) 0.0125-0.15 wt. % budesonide;
ii) a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, present at a weight ratio of no more than 5:1, relative to the weight of budesonide in the composition; and
iii) at least 90 wt. % water.
2. The composition of claim 1 , further comprising: polysorbate 80 present at a weight ratio of less than 3:1, relative to the budesonide concentration.
3. The composition of claim 1 , wherein the composition is benzalkonium chloride-free.
4. The composition of claim 1 , wherein the composition is stable following storage in a polyethylene container for 24 months at a temperature of 25° C.
5. The composition of claim 1 , wherein the composition is a dispersion.
6. The composition of claim 1 , wherein the composition is a nanodispersion.
7. A drug product, comprising: a sterile volume of the composition of claim 1 in a single dose, blow-fill-seal container.
8. An aseptic process to form a drug product composition, comprising:
i) injecting a volume of the composition of claim 1 into a sterile blow-fill-seal container; and
ii) sealing the sterile blow-fill-seal container.
9. The process of claim 8 , further comprising: sterilizing the volume of the composition of claim 1 prior to the injecting.
10. The process of claim 8 , wherein the aseptic process is exclusive of sterilization following the sealing.
11. A method of treating, preventing, or ameliorating one or more symptoms of a bronchoconstriction-related disease or disorder, comprising:
nebulizing, by a nebulizer, a unit dose of the composition of claim 1 .
12. A homogeneous, pharmaceutical composition comprising:
i) at least 0.01 wt. % budesonide;
ii) less than 1 wt. % polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer;
iii) less than 1 wt. % polysorbate 80;
iv) less than 0.02 wt. % ethylenediaminetetraacetic acid;
v) citric acid;
vi) sodium citrate; and
vii) sodium chloride,
the pharmaceutical composition exclusive of preservatives.
13. A method to prepare a precipitate-free composition, comprising:
i) forming a budesonide-containing first liquid, comprising: dispersing a quantity of budesonide micronized powder in a volume of first liquid;
ii) forming a second liquid, comprising: dissolving a quantity of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer in a volume of water; and
iii) mixing at least a portion of the budesonide-containing first liquid with a volume of the second liquid for at least 30 minutes to form the precipitate-free composition, the precipitate-free composition comprising at least 90 wt. % water,
wherein the method is exclusive of high shear mixing.
14. The method of claim 13 , wherein the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer is present at a weight ratio of no more than 4:1, relative to the weight of budesonide in the composition.
15. The method of claim 13 , wherein the composition is a dispersion.
16. The method of claim 13 , wherein the composition is a nanodispersion.
17. The method of claim 13 , wherein the concentration of budesonide is in the range of 125-1500 mcg budesonide per 2 mL of the precipitate-free composition.
18. The method of claim 13 , wherein the first liquid comprises propylene glycol and/or ethanol.
19. The method of claim 13 , wherein the second liquid comprises polysorbate 80.
20. The composition of claim 1 , wherein the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer is present at a weight ratio of no more than 4:1, relative to the weight of budesonide in the composition.
21. The composition of claim 12 , wherein the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer is present at no more than 0.1 wt. %.
22. The composition of claim 12 , wherein the polysorbate 80 is present at less than 0.1 wt. %.
23. The composition of claim 12 , wherein the ethylenediaminetetraacetic acid is present at no more than 0.01 wt. %.