Norepinephrine compositions and methods therefor
The inventive subject matter is directed to compositions and methods for ready-to-inject norepinephrine compositions with improved stability. Most preferably, compositions presented herein are substantially antioxidant free and exhibit less than 10% isomerization of R-norepinephrine and exhibit less than 5% degradation of total norepinephrine.
1. A ready-to-administer norepinephrine composition, comprising:
an aqueous solution having a pH range of between 3.7 and 4.3, wherein the aqueous solution comprises:
norepinephrine present at a concentration of between 10 μg/ml and 100 μg/ml, wherein the norepinephrine initially comprises at least 95% of R-isomer as determined by HPLC;
a chelating agent comprising a tartrate bicarboxylic acid, wherein the chelating agent is present at a concentration of between 10 μg/ml and 100 μg/ml; and
a tonicity agent,
wherein the ready-to-administer norepinephrine composition is substantially free of antioxidants; and
wherein after storage at 25±2° C. and 60±5% relative humidity over at least three months, the norepinephrine comprises at least 90% R-isomer as determined by HPLC.
2. The composition of claim 1 , wherein the tonicity agent is present in an amount to obtain osmolality of the solution of between 260 mOsm/kg and 340 mOsm/kg.
3. The composition of claim 1 , wherein the tonicity agent comprises a pharmaceutically acceptable salt and is present in an amount of between 0.6 wt % and 1.2 wt %.
4. The composition of claim 1 , wherein the tonicity agent comprises dextrose.
5. The composition of claim 1 , wherein the tonicity agent comprises NaCl.
6. The composition of claim 1 , wherein the composition is sterile.
7. The composition of claim 1 , wherein the norepinephrine comprises one or more of norepinephrine acid, norepinephrine mineral salt and norepinephrine organic salt.
8. The composition of claim 1 , wherein the norepinephrine comprises a norepinephrine organic salt.
9. The composition of claim 1 , wherein the composition is free of added buffer.
10. The composition of claim 1 , wherein the chelating agent further comprises an aminopolycarboxylic acid.