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,
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;
not more than 200 ppb of aluminum for at least 6 months from the time of manufacture of the solution;
not more than 2.0% L-cystine relative to L-cysteine; and,
a pharmaceutically acceptable carrier; and,
wherein the solution:
has a pH from about 1.0 to about 2.5;
is substantially free of visually detectable particulate matter; and,
is suitable for use as an additive in a parenteral nutrition composition for administration to an individual.
2. The solution of claim 1 , wherein the L-cysteine or a pharmaceutically acceptable salt thereof and/or hydrate thereof is present in an amount from about 20 mg/mL to about 80 mg/mL.
3. The solution of claim 1 , wherein the L-cysteine or a pharmaceutically acceptable salt thereof and/or hydrate thereof is present in an amount from about 30 mg/mL to about 70 mg/mL.
4. The solution of claim 1 , wherein the L-cysteine or a pharmaceutically acceptable salt thereof and/or hydrate thereof is present in an amount from about 40 mg/mL to about 60 mg/mL.
5. The solution of claim 1 , wherein the L-cysteine or a pharmaceutically acceptable salt thereof and/or hydrate thereof is present in an amount of about 50 mg/mL.
6. The solution of claim 1 , comprising not more than 150 ppb of aluminum for at least 12 months from the time of manufacture of the solution.
7. The solution of claim 1 , comprising not more than 120 ppb of aluminum for at least 12 months from the time of manufacture of the solution.
8. The solution of claim 1 , comprising not more than 100 ppb of aluminum for at least 12 months from the time of manufacture of the solution.
9. The solution of claim 1 , comprising not more than 80 ppb of aluminum for at least 12 months from the time of manufacture of the solution.
10. The solution of claim 1 , comprising not more than 1.0% L-cystine relative to L-cysteine.
11. The solution of claim 1 , which has a dissolved oxygen content of less than 2 ppm.
12. The solution of claim 1 , which has a dissolved oxygen content of less than 1 ppm.
13. The solution of claim 1 , wherein the pharmaceutically acceptable carrier is aqueous.
14. The solution of claim 1 , comprising not more than 200 ppb of aluminum for at least 12 months from the time of manufacture of the solution.
15. A solution of L-cysteine comprising,
L-cysteine or a pharmaceutically acceptable salt thereof and/or hydrate thereof in an amount of about 50 mg/mL;
not more than 120 ppb of aluminum for at least 6 months from the time of manufacture of the solution;
not more than 1.0% L-cystine relative to L-cysteine; and,
a pharmaceutically acceptable carrier; and,
wherein the solution:
has a pH from about 1.0 to about 2.5;
has a dissolved oxygen content of less than 1 ppm;
is substantially free of visually detectable particulate matter; and,
is suitable for use as an additive in a parenteral nutrition composition for administration to an individual.
16. A method of preparing a L-cysteine solution comprising,
preparing a mixture of a pharmaceutically acceptable carrier comprising less than about 1 ppm dissolved oxygen and L-cysteine or a pharmaceutically acceptable salt thereof and/or hydrate thereof;
adjusting the pH of said mixture to from about 1.0 to about 2.5;
transferring an amount of the pH-adjusted mixture into a single-use container;
reducing the headspace oxygen in the container; and,
sealing the container,
wherein, the L-cysteine solution comprises:
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;
not more than 200 ppb of aluminum for at least 6 months from the time of manufacture of the solution;
not more than 2.0% L-cystine relative to L-cysteine; and,
a pharmaceutically acceptable carrier;
and, wherein the solution:
has a pH from about 1.0 to about 2.5;
is substantially free of visually detectable particulate matter; and,
is suitable for use as an additive in a parenteral nutrition composition for administration to an individual.
17. The method of claim 16 , wherein the L-cysteine solution comprises:
L-cysteine or a pharmaceutically acceptable salt thereof and/or hydrate thereof in an amount of about 50 mg/mL;
not more than 120 ppb of aluminum for at least 6 months from the time of manufacture of the solution;
not more than 1.0% L-cystine relative to L-cysteine; and,
a pharmaceutically acceptable carrier;
and, wherein the solution:
has a pH from about 1.0 to about 2.5;
has a dissolved oxygen content of less than 1 ppm;
is substantially free of visually detectable particulate matter particulate matter; and,
is suitable for use as an additive in a parenteral nutrition composition for administration to an individual.