# US 7,612,102 B2 · Pre-mixed, ready-to-use pharmaceutical compositions

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- Number: US 7,612,102 B2
- Document ID: US7612102B2
- Status: Granted
- Kind: B2
- Application number: 11/788,076
- Filed: 2007-04-18
- Published: 2007-10-25
- Granted: 2009-11-03
- Earliest claimed: 2006-04-18
- Assignees: EKR Therapeutics, Inc.
- Inventors: Michelle Renee Duncan; Supriya Gupta; David Hartley Haas; Norma V. Stephens; Camellia Zamiri
- Web page: https://patentgrep.com/patent/US7612102B2

## CPC

- A61K 47/02: Inorganic compounds
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/4422: 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
- A61K 31/455: Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 47/40: Cyclodextrins; Derivatives thereof
- A61K 47/6951: {using cyclodextrin (cyclodextrins used as simple excipients A61K47/40)}
- A61P 5/14: of the thyroid hormones, e.g. T3, T4
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/02: Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 13/12: of the kidneys
- A61P 41/00: Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- C08B 37/0015: {Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes}
- C08L 5/16: Cyclodextrin; Derivatives thereof
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)

## 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.

## Claims

### Claim 1

A pharmaceutical composition for parenteral administration comprising a pre-mixed aqueous solution with a pH from about 3.6 to about 4.7 comprising:
from about 0.1 to 0.4 mg/mL nicardipine hydrochloride;
a tonicity agent selected from (i) about 4.5% to about 5% dextrose or (ii) about 0.8% to about 0.9% sodium chloride; and
a buffer in an amount to maintain pH from about 3.6 to about 4.7;
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 (i) less than a 10% decrease in the concentration of nicardipine hydrochloride and (ii) a total impurity formation of less than about 3%.

### Claim 2 (depends on 1)

The composition of claim 1, further comprising at least one pH adjuster selected from the group consisting of hydrochloric acid, sodium hydroxide and a mixture thereof.

### Claim 3 (depends on 1)

The composition of claim 1, further comprising from about 1 mg/ml to about 4 mg/ml sorbitol.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the container comprises copolyester, polyethylene or polyolefin.

### Claim 5

A pharmaceutical composition for parenteral administration comprising a pre-mixed aqueous solution with a pH from about 3.6 to about 4.7 comprising:
from about 0.1 to about 0.2 mg/mL nicardipine hydrochloride;
a tonicity agent selected from (i) about 46 to about 50 mg/mL dextrose or (ii) about 8.3 to about 9 mg/mL sodium chloride; and
a buffer in an amount to maintain pH from about 3.6 to about 4.7;
the aqueous solution contained in a pharmaceutically acceptable container comprising copolyester, polyethylene or polyolefin;
the aqueous solution when stored in the container for at least one year at room temperature exhibiting (i) less than a 10% decrease in the concentration of nicardipine hydrochloride and (ii) a total impurity formation of less than about 3%.

### Claim 6

A pharmaceutical composition for parenteral administration comprising a pre-mixed aqueous solution comprising:
from about 0.1 to about 0.2 mg/mL nicardipine hydrochloride;
a tonicity agent selected from (i) about 46 to about 50 mg/mL dextrose or (ii) about 8.3 to about 9 mg/mL sodium chloride;
from 0 mg/mL to about 4 mg/mL sorbitol; and
a buffer in an amount to maintain pH from about 3.6 to about 4.7;
the aqueous solution contained in a pharmaceutically acceptable container comprising copolyester, polyethylene or polyolefin;
the aqueous solution when stored in the container for at least one year at room temperature exhibiting (i) less than a 10% decrease in the concentration of nicardipine hydrochloride and (ii) a total impurity formation of less than about 3%.

### Claim 7

A pharmaceutical composition for parenteral administration comprising a pre-mixed aqueous solution comprising:
from about 0.1 to about 0.2 mg/mL nicardipine hydrochloride;
a tonicity agent selected from (i) about 46 to about 50 mg/mL dextrose or (ii) about 8.3 to about 9 mg/mL sodium chloride;
from 0 mg/mL to about 4 mg/mL sorbitol; and
a buffer in an amount to maintain pH from about 3.6 to about 4.7;
the aqueous solution contained in a pharmaceutically acceptable container comprising copolyester, polyethylene or polyolefin.

### Claim 8 (depends on 7)

The pharmaceutical composition for parenteral administration of claim 7. wherein the aqueous solution when stored in the container for three months at room temperature exhibits less than a 10% decrease in the concentration of nicardipine hydrochloride.

### Claim 9 (depends on 7)

The pharmaceutical composition for parenteral administration of claim 7, wherein the aqueous solution when stored in the container for three months at room temperature exhibits a total impurity formation of less than about 3%.

### Claim 10 (depends on 7)

The pharmaceutical composition for parenteral administration of claim 7, wherein the aqueous solution when stored in the container for one year at room temperature exhibits less than a 10% decrease in the concentration of nicardipine hydrochloride.

### Claim 11 (depends on 7)

The pharmaceutical composition for parenteral administration of claim 7, wherein the aqueous solution when stored in the container for one year at room temperature exhibits a total impurity formation of less than about 3%.

### Claim 12 (depends on 1)

The pharmaceutical composition for parenteral administration of claim 1, wherein the buffer is citric acid.

### Claim 13 (depends on 5)

The pharmaceutical composition for parenteral administration of claim 5, wherein the buffer is citric acid.

### Claim 14 (depends on 6)

The pharmaceutical composition for parenteral administration of claim 6, wherein the buffer is citric acid.

### Claim 15 (depends on 7)

The pharmaceutical composition for parenteral administration of claim 7, wherein the buffer is citric acid.