Parenteral dosage form of norepinephrine
The present invention relates to a ready-to-administer parenteral dosage form of norepinephrine which comprises an aqueous solution of norepinephrine, having an anti-oxidant which is not a sulfite anti-oxidant, wherein the dosage form is stable at room temperature for prolonged period of time.
1. A ready-to-administer parenteral dosage form comprising
a. an aqueous solution comprising
I. a therapeutically effective amount of norepinephrine or its pharmaceutically acceptable salt and
II. an antioxidant which is not a sulphite antioxidant,
wherein the antioxidant is butylated hydroxyl anisole,
wherein butylated hydroxyl anisole is present in the aqueous solution in an amount ranging from about 0.001 mg/ml to about 0.01 mg/ml,
wherein the parenteral dosage form is stable at room temperature, and
wherein the value of total impurities in the aqueous solution is not more than 2.0% by weight after storage at room temperature for at least 12 months.
2. The ready-to-administer parenteral dosage form as claimed in claim 1 , wherein norepinephrine is present in an amount ranging from about 0.001 mg/ml to about 0.2 mg/ml.
3. The ready-to-administer parenteral dosage form as claimed in claim 1 , wherein the norepinephrine or its pharmaceutically acceptable salt is norepinephrine bitartarate.
4. The ready-to-administer parenteral dosage form as claimed in claim 3 , wherein the norepinephrine bitartarate is present in an amount ranging from about 0.002 mg/ml to about 0.4 mg/ml.
5. The ready-to-administer parenteral dosage form as claimed in claim 1 , wherein the pH of the aqueous solution is in a range of about 3.0 to about 4.5.
6. The ready-to-administer parenteral dosage form as claimed in claim 1 , wherein the aqueous solution is in a container, which optionally is further packaged in a secondary packaging, wherein either the container or the secondary packaging is designed to protect the aqueous solution from light.
7. The ready-to-administer parenteral dosage form as claimed in claim 6 , wherein the container comprises a material selected from the group comprising polyolefin polymers, polyethylene, polypropylene, cyclo olefin polymers, cyclo olefin copolymers, polypropylene based polyolefin polymers, polycarbonates, modified polyolefin-polyethylene polymers, and styrene-polyolefin based polymers and block co-polymers.
8. The ready-to-administer parenteral dosage form as claimed in claim 6 , wherein the secondary packaging comprises an aluminum pouch.
9. The ready-to-administer parenteral dosage form as claimed in claim 6 , wherein the container is a pre-filled syringe and wherein norepinephrine is present in the aqueous solution in an amount ranging from about 0.05 mg/ml to about 0.2 mg/ml.
10. The ready-to-administer parenteral dosage form as claimed in claim 6 , wherein the container is an infusion bag and wherein norepinephrine is present in the aqueous solution in an amount ranging from about 0.004 mg/ml to about 0.15 mg/ml.
11. The ready-to-administer parenteral dosage form as claimed in claim 1 ,
wherein the aqueous solution when stored at room temperature for twelve months has less than 4% of S-isomer content.