of nicardipine or its salts; treating hypertension; storage stability
Inventors
Duncan, Michelle Renee • Gupta, Supriya • Haas, David Hartley • Stephens, Norma V. • Zamiri, Camellia
Assignees
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Publication Number
US-7659291-B2
Publication Date
2010-02-09
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 relates to a pre-mixed aqueous nicardipine-containing composition for parenteral administration that requires no dilution before administration. The composition includes nicardipine or nicardipine hydrochloride, a tonicity agent, and a buffer, and has a pH from about 3.6 to about 4.7.
The compositions are characterized by maintaining nicardipine concentration and limiting degradation products during storage in a pharmaceutically acceptable container. In some embodiments, the solution does not come into contact with polar polymers, and room-temperature storage for at least three months or at least one year is associated with less than a 10% decrease in nicardipine concentration and total impurity formation of less than about 3%.
Additional aspects describe optional cosolvents and complexing agents, including cyclodextrins such as CAPTISOL, SBEBCD, and 2HPBCD, to solubilize and stabilize higher nicardipine concentrations while enabling lower fluid volumes for volume-restricted patients. The formulations include defined ranges for nicardipine hydrochloride, tonicity agents, and buffers, including citric acid, and may incorporate components such as sorbitol.
Claims Coverage
The independent claims cover four distinct method categories centered on ready-to-administer, premixed nicardipine formulations with specified pH, tonicity, buffer, and stability criteria. Across the independent claims, inventive features are driven by no dilution, a defined acidic pH range, specific composition components, defined storage stability, and container compatibility to avoid contact with polar polymers.
Ready-to-administer nicardipine composition requiring no dilution with acidic pH and defined stability
A method for treating acute elevations of blood pressure in a human subject comprising parenterally administering a composition comprising nicardipine or a pharmaceutically acceptable salt thereof; a tonicity agent; and a buffer; wherein the composition requires no dilution before administration and has a pH from about 3.6 to about 4.7, the composition when stored in container for at least three months at room temperature exhibiting less than a 10% decrease in the concentration of nicardipine or pharmaceutically acceptable salt thereof and total impurity formation of less than about 3%.
Ready-to-administer nicardipine composition for hypotension induction with acidic pH and defined stability
A method for inducing hypotension in a human subject comprising parenterally administering a composition comprising nicardipine or a pharmaceutically acceptable salt thereof; a tonicity agent; and a buffer; wherein the composition requires no dilution before administration and has a pH from about 3.6 to about 4.7, the composition when stored in a container for at least three months at room temperature exhibiting less than a 10% decrease in the concentration of nicardipine or pharmaceutically acceptable salt thereof and total impurity formation of less than about 3%.
Premixed aqueous nicardipine hydrochloride solution with tonicity agent and citric acid in a container avoiding polar polymer contact and long-term stability
A method for treating acute elevations of blood pressure in a human subject comprising parenterally administering a pre-mixed aqueous solution with a pH from about 3.6 to about 4.7 comprising nicardipine hydrochloride; a tonicity agent selected from about 4.5% to about 5% dextrose or about 0.8% to about 0.9% sodium chloride; citric acid; the aqueous solution contained in a pharmaceutically acceptable container such that the solution does not come into contact with polar polymers; the aqueous solution when stored in the container for at least one year at room temperature exhibiting less than a 10% decrease in the concentration of nicardipine hydrochloride and total impurity formation of less than about 3%; wherein the administering does not comprise diluting the aqueous solution prior to administration.
Premixed aqueous nicardipine hydrochloride solution for hypotension induction with tonicity agent and citric acid in a container avoiding polar polymer contact and long-term stability
A method for inducing hypotension in a human subject comprising parenterally administering to a subject in need thereof, a pre-mixed aqueous solution with a pH from about 3.6 to about 4.7 comprising nicardipine hydrochloride; a tonicity agent selected from about 4.5% to about 5% dextrose or about 0.8% to about 0.9% sodium chloride; citric acid; the aqueous solution contained in a pharmaceutically acceptable container such that the solution does not come into contact with polar polymers; the aqueous solution when stored in the container for at least one year at room temperature exhibiting less than a 10% decrease in the concentration of nicardipine hydrochloride and total impurity formation of less than about 3%; wherein the administering does not comprise diluting the aqueous solution prior to administration.
Across the independent claims, the core inventive coverage is directed to parenteral treatment or induction of hypotension using a premixed aqueous nicardipine or nicardipine hydrochloride composition that requires no dilution, has an acidic pH within about 3.6 to about 4.7, includes a tonicity agent and buffer, and maintains performance after room-temperature storage with less than 10% nicardipine concentration decrease and total impurities less than about 3%. The composition may further be constrained by container conditions that prevent solution contact with polar polymers, and specific versions require storage stability for at least one year.
Stated Advantages
Provides a composition that requires no dilution before administration.
Maintains nicardipine concentration with less than a 10% decrease after storage in the container at room temperature for at least three months or at least one year, depending on the claim.
Limits total impurity formation to less than about 3% after room-temperature storage.
Reduces issues associated with diluted ampul use, including pH variability and concentration loss and impurity formation under use conditions.
Documented Applications
Treating acute elevations of blood pressure in a human subject in need thereof.
Inducing hypotension in a human subject in need thereof.
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