# US 2013/0158079 A1 · Clevidipine emulsion formulations containing antimicrobial agents

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- Number: US 2013/0158079 A1
- Document ID: US20130158079A1
- Status: Published application
- Kind: A1
- Application number: 13/765,613
- Filed: 2013-02-12
- Published: 2013-06-20
- Earliest claimed: 2013-02-12
- Assignees: The Medicines Company
- Inventors: Rajeshwar Motheram; Gregory Charles Williams
- Web page: https://patentgrep.com/patent/US20130158079A1

## CPC

- A61K 31/4422: 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
- A01N 37/44: containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
- A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)}
- A61K 31/4418: having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
- 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)
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS

## Abstract

Pharmaceutical formulations comprising clevidipine in an oil-in-water formulation that is resistant to microbial growth and stable against the formation of impurities.

## Claims

### Claim 1

A pharmaceutical formulation comprising,
(a) an effective amount of clevidipine, or a pharmaceutically acceptable salt or ester,
(b) an antimicrobial agent, present at about 0.001 to about 1.5% w/v,
(c) a lipid,
(d) an emulsifier,
(e) a tonicity modifier, and
(f) water
wherein the formulation is resistant to microbial growth.

### Claim 2 (depends on 1)

The pharmaceutical formulation of claim 1, wherein the antimicrobial agent is selected from the group consisting of benzyl alcohol, EDTA, sodium ascorbate, citric acid, and mixtures, derivates, and salts thereof.

### Claim 3 (depends on 2)

The pharmaceutical formulation of claim 2, wherein the antimicrobial agent is EDTA present at about 0.001 to about 0.025% w/v.

### Claim 4 (depends on 1)

The pharmaceutical formulation of claim 1, wherein the lipid is selected from the group consisting of soybean oil, safflower seed oil, olive oil, cottonseed oil, sunflower oil, sesame oil, peanut oil, corn oil, medium chain triglycerides, triacetin, propylene glycol diesters, monoglycerides, and a mixture of two or more thereof.

### Claim 5 (depends on 1)

The pharmaceutical formulation of claim 1, wherein the emulsifier is selected from the group consisting of egg yolk phospholipids, soybean phospholipids, synthetic phosphatidyl cholines, purified phosphatidyl cholines and hydrogenated phosphatidyl choline, and mixtures of two or more thereof.

### Claim 6 (depends on 1)

The pharmaceutical formulation of claim 1, further comprising an antioxidant selected from the group consisting of sodium ascorbate, sodium citrate, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, tocopherol, and a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 1)

The formulation of claim 1 having a pH of about 6.0 to about 8.8.

### Claim 8 (depends on 3)

The pharmaceutical formulation of claim 3, further comprising sodium ascorbate at about 0.01 to about 1% w/v.

### Claim 9 (depends on 3)

The pharmaceutical formulation of claim 3, further comprising sodium citrate at about 0.005 to about 0.5% w/v.

### Claim 10 (depends on 3)

The pharmaceutical formulation of claim 3, further comprising a co-emulsifier wherein the co-emulsifier is selected from the group consisting of glycerol, glycerin, poloxamers, Cremophor™, poloxamines, polyoxyethylene stearates, polyoxyethylene sorbitan fatty acid esters, sorbitan fatty acid esters, polysorbates, tocopherol PEG succinate, cholic acid, deoxycholic acid, oleic acid, and pharmaceutically acceptable salts thereof

### Claim 11 (depends on 3)

The pharmaceutical formulation of claim 3 further comprising oleic acid at about 0.01 to about 2.0% w/v.

### Claim 12 (depends on 9)

The pharmaceutical formulation of claim 9, wherein H324/78 is present in the formulation at about 0.2% or less.

### Claim 13 (depends on 1)

The formulation of claim 1 wherein microbial growth is delayed or retarded such that there is less than 10-fold (1 log) increase in viable microbial colonies over a 24-hour period.