Ready-to-use ketamine premix formulation
The invention relates to a sterile, ready-to-use, stable aqueous solution of ketamine suitable for direct intravenous infusion to a patient in need thereof, wherein the composition is disposed within a sealed infusion container as a premixture. The invention further relates to aqueous solutions of ketamine that are free of antimicrobials such as benzethonium chloride and are shelf-stable. The pharmaceutical compositions can be used, for example, wherein the subject is in need of anesthesia for a diagnostic or a surgical procedure.
1. A ketamine product comprising an aqueous ketamine solution comprising about 0.5 to about 2.5 mg/mL ketamine, a tonicity adjusting agent, and water for injection, wherein the ketamine solution is preservative-free and anti-microbial free, wherein the ketamine product is sterile and ready-to-use (RTU), wherein the pH of the aqueous ketamine solution is about 3.5 to about 5.5, and wherein the ketamine product has a shelf-life of more than six months when stored at a controlled room temperature between 15-30° C.
2. The ketamine product of claim 1 , wherein the ketamine product has been terminally sterilized.
3. The ketamine product of claim 1 , wherein the ketamine is at a concentration of about 1 mg/mL to about 2 mg/mL.
4. The ketamine product of claim 1 , wherein the aqueous ketamine solution is contained in an infusion bag comprising at least one port sealed with a closure.
5. The ketamine product of claim 1 , wherein the aqueous ketamine solution has an osmolality of about 270-330 mOsmol/kg.
6. The ketamine product of claim 4 , wherein the at least one port comprises a multilayer polyolefin and styrene block copolymer tube material.
7. The ketamine product of claim 4 , wherein the closure comprises a plastic material.
8. The ketamine product of claim 4 , wherein the closure is a twist-off closure and comprises a membrane that creates a barrier, splitting the twist-off closure in two parts, wherein a first of the two parts is an inferior part of the membrane that is in direct contact with the ketamine solution, and the second of the two parts is a superior part of the membrane that is in contact with a zone that forms an air chamber into the closure.
9. The ketamine product of claim 7 , wherein the closure is a twist-off closure that comprises polypropylene (PP), low density polyethylene (LDPE), polyolefin block copolymer, or any combination thereof.
10. The ketamine product of claim 4 , wherein the infusion bag comprises a flexible multilayer film comprising a polymer selected from the group consisting of polyethylene, polypropylene, modified polyolefin-polyethylene polymers, styrene-polyolefin based polymers, block copolymers, and a combination thereof.
11. The ketamine product of claim 4 , wherein the infusion bag comprises a flexible multilayer film comprising 2 to 5 layers, wherein at least one layer comprises polypropylene styrene-block copolymer.
12. The ketamine product of claim 4 , wherein the infusion bag comprises a 3-layer film wherein at least one layer comprises polypropylene styrene-block copolymer.
13. The ketamine product of claim 4 , wherein the infusion bag is contained within an overwrap.
14. The ketamine product of claim 13 , wherein the overwrap comprises four layers comprising polyester, aluminum, polypropylene, and polyester.
15. The ketamine product of claim 1 , wherein the ketamine product has been autoclaved.
16. A ketamine product comprising an aqueous ketamine solution comprising about 0.5 to about 2.5 mg/mL ketamine, a tonicity adjusting agent, and water for injection, wherein the ketamine solution is preservative-free and anti-microbial free, wherein the pH of the aqueous ketamine solution is about 3.5 to about 5.5, and wherein the ketamine solution is contained in a terminally sterilized, ready-to-use infusion container, and wherein the ketamine product has a shelf-life of more than six months when stored at a controlled room temperature between 15-30° C.
17. The ketamine product of claim 16 , wherein the tonicity adjustment agent comprises sodium chloride, dextrose, glycerin, mannitol, potassium chloride, or any combination thereof.
18. The ketamine product of claim 1 , wherein the ketamine or a pharmaceutically acceptable salt thereof is chemically stable following 24 months of storage at 25° C.±2° C. with relative humidity (RH) at 40%±5%.
19. The ketamine product of claim 1 , wherein the ketamine content of the aqueous ketamine solution after accelerated storage at 40° C.±2° C./<25% RH for 6 months is greater than 97%; and/or wherein the ketamine content of the aqueous ketamine solution after long-term storage for 12 months at 25° C.±2° C./40% RH±5% RH is 97% or greater compared to the ketamine content before storage.
20. A method of treating a subject in need of analgesia, comprising administering the ketamine product of claim 1 to the subject as a continuous infusion.
21. A ketamine product comprising an aqueous ketamine solution comprising about 0.5 to about 2.5 mg/mL ketamine, a tonicity adjusting agent, and water for injection, wherein the ketamine solution is preservative-free and anti-microbial free, wherein the pH of the aqueous ketamine solution is about 3.5 to about 5.5, wherein the ketamine solution is contained in an infusion bag, wherein the ketamine product has been aseptically filled, and wherein the ketamine product is sterile and ready-to-use (RTU), and wherein the ketamine product has a shelf-life of more than six months when stored at a controlled room temperature between 15-30° C.
22. The ketamine product of claim 16 , wherein the ketamine or a pharmaceutically acceptable salt thereof is chemically stable following 24 months of storage at 25° C.±2° C. with relative humidity (RH) at 40%±5%.
23. The ketamine product of claim 21 , wherein the ketamine or a pharmaceutically acceptable salt thereof is chemically stable following 24 months of storage at 25° C.±2° C. with relative humidity (RH) at 40%±5%.