Stable, highly pure L-cysteine compositions for injection and methods of use
The subject matter described herein is directed to stable L-cysteine compositions for injection, comprising: L-cysteine or a pharmaceutically acceptable salt thereof and/or hydrate thereof in an amount from about 10 mg/mL to about 100 mg/mL; Aluminum in an amount from about 1.0 parts per billion (ppb) to about 250 ppb; cystine in an amount from about 0.01 wt % to about 2 wt % relative to L-cysteine; pyruvic acid in an amount from about 0.01 wt % to about 2 wt % relative to L-cysteine; a pharmaceutically acceptable carrier, comprising water; headspace O 2 that is less than 1.0%; dissolved oxygen present in the carrier in an amount from about 0.01 parts per million (ppm) to about 1 ppm, wherein the composition is enclosed in a single-use container having a volume of from 10 mL to 100 mL. Also described are compositions for a total parenteral nutrition regimen and methods for their use.
1. A solution of L-cysteine comprising,
a pharmaceutically acceptable carrier,
about 50 mg/mL of L-cysteine hydrochloride monohydrate, or equivalent amount of a pharmaceutically acceptable L-cysteine or a salt or hydrate thereof,
less than about 150 ppb of aluminum,
a pH from about 1.0 to about 2.5, and
wherein the solution is substantially free of visually detectable particulate matter and suitable for use as an additive in a parenteral nutrition composition for administration to an individual.
2. The solution of claim 1 , which comprises less than about 100 ppb of aluminum.
3. The solution of claim 1 , which comprises less than about 50 ppb of aluminum.
4. The solution of claim 1 , which comprises less than about 20 ppb of aluminum.
5. The solution of claim 1 , which comprises less than about 10 ppb of aluminum.
6. The solution of claim 1 , which comprises from about 1 ppb to about 150 ppb of aluminum.
7. The solution of claim 1 , which has a dissolved oxygen content of less than 2 ppm.
8. The solution of claim 1 , wherein the pH is about 1.8 and in which the solution is substantially free of cystine precipitates.
9. The solution of claim 1 , wherein the solution is substantially free of visually detectable particulate matter when stored for 18 months at about 25° C. and about 60% relative humidity.
10. The solution of claim 9 , wherein the pharmaceutically acceptable carrier is aqueous.
11. The solution of claim 1 , wherein the solution is essentially free of cystine precipitates.
12. A solution of L-cysteine comprising,
a pharmaceutically acceptable carrier,
about 50 mg/mL of L-cysteine hydrochloride monohydrate, or equivalent amount of a pharmaceutically acceptable L-cysteine or a salt or hydrate thereof,
less than about 150 ppb of aluminum, and
a pH from about 1.0 to about 2.5,
wherein the solution is substantially free of visually detectable particulate matter for at least 6 months from the time of manufacture of the solution and is suitable for use as an additive in a parenteral nutrition composition for administration to a neonate or infant.
13. The solution of claim 12 , wherein the solution is substantially free of visually detectable particulate matter for at least 9 months from the time of manufacture of the solution.
14. The solution of claim 12 , wherein the solution is substantially free of visually detectable particulate matter for at least 12 months from the time of manufacture of the solution.
15. The solution of claim 12 , wherein the solution is substantially free of visually detectable particulate matter for at least 24 months from the time of manufacture of the solution.
16. The solution of claim 12 , wherein the solution is essentially free of cystine precipitates.
17. A solution of L-cysteine comprising,
a pharmaceutically acceptable carrier,
about 50 mg/mL of L-cysteine hydrochloride monohydrate, or equivalent amount of a pharmaceutically acceptable L-cysteine or a salt or hydrate thereof, in a low oxygen environment,
less than about 150 ppb of aluminum, and
a pH from about 1.0 to about 2.5,
wherein the solution is substantially free of visually detectable particulate matter and is suitable for use as an additive in a parenteral nutrition composition for administration to a neonate or infant.
18. The solution of claim 17 , wherein the solution is substantially free of visually detectable particulate matter for at least 6 months after the time of manufacture of the solution.
19. The solution of claim 17 , wherein the solution is substantially free of visually detectable particulate matter for at least 9 months after the time of manufacture of the solution.
20. The solution of claim 17 , wherein the solution is substantially free of visually detectable particulate matter for at least 12 months after the time of manufacture of the solution.
21. The solution of claim 17 , wherein the solution is substantially free of visually detectable particulate matter for at least 24 months after the time of manufacture of the solution.
22. The solution of claim 17 , wherein the solution has a dissolved oxygen content of less than about 5 ppm.
23. The solution of claim 17 , wherein the solution has a dissolved oxygen content of less than about 2 ppm.
24. The solution of claim 17 , wherein the solution has a dissolved oxygen content of less than about 1 ppm.
25. The solution of claim 17 , wherein the solution has a dissolved oxygen content of about 0.4 ppm to about 3.8 ppm.
26. The solution of claim 17 , wherein the solution is essentially free of cystine precipitates.
27. The solution of claim 18 , wherein the solution is essentially free of cystine precipitates.