Patent
Storage stable sterile ready-to-administer formulations comprising N-acetylcysteine are presented with desirable stability characteristics. In preferred aspects, formulations comprise low quantities of one or more chelating agents, contain N-acetylcysteine at a concentration of 25 mg/mL or 50 mg/mL, and are packaged in a suitable format, such as a polymeric bag with a metalized overwrap and a non-contact oxygen scavenger.
1. A sterile and ready-to-administer N-acetylcysteine composition, comprising:
an aqueous solution containing N-acetylcysteine at a concentration suitable for direct administration via intravenous injection to a patient without dilution prior to administration;
wherein the composition has a pH of between 5 and 9 and comprises a chelating agent at a concentration of between 10 and 60 mcg/mL; and
wherein the composition contains, after storage over at least three weeks at 80° C., equal or less than 8% total impurities generated from degradation of the N-acetylcysteine.
2. The composition of claim 1 , wherein the N-acetylcysteine concentration is 25 mg/mL.
3. The composition of claim 1 , wherein the N-acetylcysteine concentration is 50 mg/mL.
4. The composition of claim 1 , wherein the chelating agent comprises EDTA.
5. The composition of claim 1 , wherein the composition is free of preservatives.
6. A kit comprising:
a primary container that contains the composition of claim 1 ;
a secondary container enclosing the primary container, and a non-contact oxygen absorbing agent in a space between the primary and secondary container;
wherein the primary container contains between 100 and 500 mL of the composition; and
wherein the secondary container is impermeable to light or comprises a metal or metal layer.
7. A sterile and ready-to-administer N-acetylcysteine composition, comprising:
an aqueous solution containing N-acetylcysteine at a concentration suitable for direct administration via intravenous injection to a patient without dilution prior to administration;
wherein the composition has a pH of between 6.0 and 7.5 and comprises a chelating agent at a concentration of between 10 and 60 mcg/mL; and
wherein the composition contains, after storage over at least three weeks at 80° C., equal or less than 3% of related substance RC-B generated from degradation of the N-acetylcysteine.
8. The composition of claim 7 , wherein the N-acetylcysteine concentration is 25 mg/mL.
9. The composition of claim 7 , wherein the N-acetylcysteine concentration is 50 mg/mL.
10. The composition of claim 7 , wherein the composition is free of preservatives.
11. The composition of claim 7 , wherein the pH is 7.0±0.2.
12. The composition of claim 7 , wherein the composition contains, after storage over at least three weeks at 80° ° C., equal or less than 8% total impurities generated from degradation of the N-acetylcysteine.
13. A kit comprising:
a primary container that contains the composition of claim 7 ;
a secondary container enclosing the primary container, and a non-contact oxygen absorbing agent in a space between the primary and secondary container;
wherein the primary container contains between 100 and 500 mL of the composition; and
wherein the secondary container is impermeable to light or comprises a metal or metal layer.
14. A sterile and ready-to-administer N-acetylcysteine composition, comprising:
an aqueous solution containing N-acetylcysteine at a concentration suitable for direct administration via intravenous injection to a patient without dilution prior to administration;
wherein the composition has a pH of between 6.0 and 7.5 and comprises a chelating agent, wherein the chelating agent is present at a concentration of less than 100 mcg/mL; and
wherein the composition contains, after storage over at least three weeks at 80° ° C., equal or less than 7% total impurities generated from degradation of the N-acetylcysteine.
15. The composition of claim 14 , wherein the N-acetylcysteine concentration is 25 mg/mL.
16. The composition of claim 14 , wherein the N-acetylcysteine concentration is 50 mg/mL.
17. The composition of claim 14 , wherein the chelating agent comprises EDTA.
18. The composition of claim 14 , wherein the composition is free of preservatives.
19. The composition of claim 14 , wherein the pH is 7.0±0.2.
20. A kit comprising:
a primary container that contains the composition of claim 14 ;
a secondary container enclosing the primary container, and a non-contact oxygen absorbing agent in a space between the primary and secondary container;
wherein the primary container contains between 100 and 500 mL of the composition; and
wherein the secondary container is impermeable to light or comprises a metal or metal layer.