N-ACETYLCYSTEINE COMPOSITIONS AND METHODS
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 method of preparing a sterile and ready-to-administer N-acetylcysteine composition, comprising:
preparing a composition by combining an aqueous solvent, a chelating agent, and N-acetylcysteine,
wherein the N-acetylcysteine is provided in the composition at a concentration suitable for direct administration to a patient via intravenous injection without dilution prior to administration,
wherein the cheating agent is provided in the composition at a concentration of between 10 and 60 mcg/mL, and
wherein the composition has a pH of between 5 and 9.
2 . The method of claim 1 , 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.
3 . The method of claim 1 , further comprising deoxygenating the aqueous solvent.
4 . The method of claim 3 , wherein deoxygenating the aqueous solvent comprises sparging with at least one inert gas, agitation under vacuum, and/or providing an enzymatic system sufficient to deplete dissolved oxygen.
5 . The method of claim 1 , wherein the method further comprises filling the composition into a container.
6 . The method of claim 5 , wherein the container comprises a headspace that is oxygen-reduced or oxygen-depleted.
7 . The method of claim 5 , wherein the method further comprises co-packaging the container in a secondary container that comprises an oxygen scavenger.
8 . The method of claim 7 , wherein the secondary container is impermeable to light.
9 . The method of claim 7 , wherein the secondary container comprises a metal.
10 . The method of claim 5 , further comprising sterilizing the container.
11 . The method of claim 10 , wherein sterilizing the container comprises autoclaving.
12 . The method of claim 5 , wherein the container contains between 100 and 500 mL of the composition.
13 . The method of claim 1 , further comprising sterilizing the composition.
14 . The method of claim 13 , wherein sterilizing the composition comprises one or more of filtration, heat sterilization, autoclaving, radiation, and gas sterilization.
15 . The method of claim 5 , wherein the composition is provided in the container via a blow-fill-seal process.
16 . The method of claim 1 , wherein the N-acetylcysteine concentration is 25 mg/mL.
17 . The method of claim 1 , wherein the N-acetylcysteine concentration is 50 mg/mL.
18 . The method of claim 1 , wherein the chelating agent comprises EDTA.
19 . The method of claim 1 , wherein the composition is free of preservatives.
20 . The method of claim 1 , wherein the pH is 7.0±0.2.