# US 10,869,848 B2 · Carmustine pharmaceutical composition

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- Number: US 10,869,848 B2
- Document ID: US10869848B2
- Status: Granted
- Kind: B2
- Application number: 16/417,013
- Filed: 2019-05-20
- Published: 2019-09-05
- Granted: 2020-12-22
- Earliest claimed: 2014-11-14
- Assignees: Navinta III Inc
- Applicants: Mahendra R. Patel
- Inventors: Mahendra R. Patel
- Web page: https://patentgrep.com/patent/US10869848B2

## CPC

- A61K 31/175: having the group [IMAGE cpc-sch-A61K-0950.gif] , >N—C(O)—N=N— or[IMAGE cpc-sch-A61K-0951.gif] , e.g. carbonohydrazides, carbazones, semicarbazides, semicarbazones; Thioanalogues thereof
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61P 19/00: Drugs for skeletal disorders
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 35/00: Antineoplastic agents
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- 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

## Abstract

The present invention provides pharmaceutical formulations of lyophilized carmustine suitable for pharmaceutical use. The present invention further provides methods of producing lyophilized carmustine. The pharmaceutical formulations can be used for any disease that is sensitive to treatment with carmustine, such as neoplastic diseases.

## Claims

### Claim 1

A process of preparing a lyophilized carmustine pharmaceutical composition comprising the steps of:
(a) dissolving 3-400 mg/mL carmustine in a solvent consisting essentially of dehydrated t-butanol a second and dehydrated alcohol to obtain a carmustine solution,
(b) freezing the carmustine solution of step (a), and
(c) removing the dehydrated t-butanol and dehydrated alcohol at a first freeze-drying temperature after the step (b) of freezing.

### Claim 2 (depends on 1)

The process of claim 1, further comprising a step (d) of freeze-drying at a secondary drying temperature that is higher than the first freeze-drying temperature.

### Claim 3 (depends on 1)

The process of claim 1, wherein the ratio of dehydrated t-butanol:dehydrated alcohol is 5:95 (v/v) to 95:5 (v/v).

### Claim 4 (depends on 3)

The process of claim 3, wherein the solvent is a blend of dehydrated t-butanol and a second dehydrated alcohol selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, and butanol, and
the step (a) of dissolving comprises dissolving carmustine in the second dehydrated alcohol first to form a solution before the dehydrated t-butanol is added.

### Claim 5 (depends on 4)

The process of claim 4, wherein the second dehydrated alcohol is ethanol or isopropanol.

### Claim 6 (depends on 4)

The process of claim 4, wherein the dehydrated t-butanol and the second dehydrated alcohol are present in a ratio of 90:10 (v/v) t-butanol:second dehydrated alcohol.

### Claim 7 (depends on 4)

The process of claim 4, wherein the dehydrated t-butanol and the second dehydrated alcohol are present in a ratio of 95:5 (v/v) t-butanol:second dehydrated alcohol.

### Claim 8 (depends on 1)

The process of claim 1, wherein the solvent blend consists essentially of dehydrated t-butanol and 5% (v/v) to 15% (v/v) of the dehydrated alcohol.

### Claim 9 (depends on 1)

The process of claim 1, wherein
the freezing step is performed at a temperature of about −50° C. or below and held for greater than about 2 hours and
the first drying temperature is about −45° C. to about −30° C.

### Claim 10 (depends on 2)

The process of claim 2, wherein
the freezing step is performed at a temperature of about −50° C. or below and held for greater than about 2 hours and
the drying step is performed at a first drying temperature of about −45° C. to about −30° C. and a secondary drying temperature of about −10° C. to about 25° C.

### Claim 11 (depends on 1)

The process of claim 1, wherein a pressure during the step of removing is 100 mT to 900 mT.

### Claim 12 (depends on 1)

The process of claim 1, further comprising the step of filtering the solution through 0.22μ filter prior to the step of freezing.

### Claim 13 (depends on 1)

The process of claim 1, wherein 10 mg/mL to 200 mg/mL of carmustine is dissolved in the step of dissolving.

### Claim 14 (depends on 1)

The process of claim 1, wherein 25 mg/mL to 150 mg/mL of carmustine is dissolved in the step of dissolving.

### Claim 15 (depends on 1)

The process of claim 1, wherein 50 mg/mL to 100 mg/mL of carmustine is dissolved in the step of dissolving.

### Claim 16 (depends on 14)

The process of claim 14, wherein the solvent is a 95:5 blend of t-butanol:ethanol.

### Claim 17 (depends on 14)

The process of claim 14, wherein the solvent is a 95:5 blend of t-butanol:isopropanol.