Pre-mixed, ready-to-use pharmaceutical compositions
Inventors
Duncan, Michelle Renee • Gupta, Supriya • Haas, David Hartley • Nenonene, Norma V. • Zamiri, Camellia
Assignees
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Publication Number
US-10758616-B2
Publication Date
2020-09-01
Expiration Date
Abstract
Provided herein are ready-to-use premixed pharmaceutical compositions of nicardipine or a pharmaceutically acceptable salt and methods for use in treating cardiovascular and cerebrovascular conditions.
Core Innovation
The invention is a pharmaceutical composition for parenteral administration comprising a pre-mixed aqueous solution containing from about 0.1 to 0.4 mg/mL nicardipine or a pharmaceutically acceptable salt thereof and a tonicity agent. The aqueous solution is contained in a pharmaceutically acceptable container such that the solution is in contact with non-polar polymers. The composition requires no dilution before administration and is buffered to a pH from about 3.6 to about 4.4.
The invention further defines a storage-stability profile for the pre-mixed aqueous solution in the container. When stored in the container for at least three months at room temperature, the aqueous solution exhibits less than a 10% decrease in the concentration of nicardipine or the pharmaceutically acceptable salt thereof and a total impurity formation of less than about 3%. Dependent refinements specify particular container polymer materials selected from non-polar polymers including copolyester, polyethylene, or polyolefin.
Additional refinements specify tonicity-agent composition within the buffered, ready-to-use solution. In particular, the tonicity agent comprises dextrose, and the dextrose may be present at about 4.5% to about 5% w/v. The disclosed composition thus combines buffered pre-mixed nicardipine-containing aqueous formulation, container-contact with non-polar polymers, and defined concentration and impurity stability criteria without dilution before administration.
Claims Coverage
The independent claim set is grounded in a single independent claim defining a buffered, pre-mixed, dilution-free nicardipine aqueous formulation with tonicity agent, defined container-contact with non-polar polymers, and specific room-temperature storage stability thresholds. Dependent claims further narrow formulation components and storage criteria.
Pre-mixed aqueous nicardipine solution requiring no dilution
A pharmaceutical composition for parenteral administration comprising a pre-mixed aqueous solution comprising from about 0.1 to 0.4 mg/mL nicardipine or a pharmaceutically acceptable salt thereof and a tonicity agent, wherein the composition requires no dilution before administration.
Buffered aqueous solution at pH about 3.6 to about 4.4
The aqueous solution is buffered to a pH from about 3.6 to about 4.4.
Container in contact with non-polar polymers
The aqueous solution is contained in a pharmaceutically acceptable container such that the solution is in contact with non-polar polymers.
Room-temperature storage stability with concentration and impurity limits
When stored in the container for at least three months at room temperature, the composition exhibits less than a 10% decrease in the concentration of nicardipine or pharmaceutically acceptable salt thereof and total impurity formation of less than about 3%.
Specific nicardipine concentration sub-range
The composition comprises nicardipine or a pharmaceutically acceptable salt thereof in an amount of about 0.1 to 0.2 mg/mL.
Tonicity agent comprising dextrose
The composition includes a tonicity agent that comprises dextrose.
Dextrose concentration about 4.5% to about 5% w/v
The composition further includes dextrose at a concentration of about 4.5% to about 5% w/v.
Non-polar polymers include copolyester, polyethylene, or polyolefin
The non-polar polymers include copolyester, polyethylene or polyolefin.
Extended storage time criterion at room temperature
When stored in a container for at least one year at room temperature, the aqueous nicardipine-containing solution shows less than a 10% decrease in nicardipine concentration and less than about 3% total impurity formation.
Across the independent and dependent claim set, the core inventive coverage is a buffered, pre-mixed aqueous nicardipine or salt composition with a tonicity agent that requires no dilution, maintained in a container that contacts non-polar polymers, and meeting defined room-temperature stability criteria for concentration decrease and total impurity formation.
Stated Advantages
Requires no dilution before administration.
Maintains less than a 10% decrease in nicardipine concentration after at least three months at room temperature.
Limits total impurity formation to less than about 3% after at least three months at room temperature.
Maintains less than a 10% decrease in nicardipine concentration after at least one year at room temperature.
Limits total impurity formation to less than about 3% after at least one year at room temperature.
Documented Applications
Parenteral administration of the nicardipine-containing pharmaceutical composition, including continuous intravenous infusion.
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