# US 11,304,961 B2 · Compositions comprising dexamethasone

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- Number: US 11,304,961 B2
- Document ID: US11304961B2
- Status: Granted
- Kind: B2
- Application number: 16/743,136
- Filed: 2020-01-15
- Published: 2020-05-14
- Granted: 2022-04-19
- Earliest claimed: 2017-12-18
- Assignees: Dexcel Pharma Technologies Ltd.
- Applicants: Dexcel Pharma Technologies Ltd.
- Inventors: Caterina Kreyenborg; Elisabeth Meimberg; Corinna Tissen; Karl-Heinz Bannefeld; Tomer Gold
- Web page: https://patentgrep.com/patent/US11304961B2

## CPC

- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/1694: {resulting in granules or microspheres of the matrix type containing more than 5% of excipient}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/2059: {Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin}
- A61K 31/454: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- 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

A pharmaceutical composition useful for the treatment of multiple myeloma in combination with an anti-cancer drug is provided. The pharmaceutical composition includes high-dose dexamethasone or a pharmaceutically acceptable salt or solvate thereof.

## Claims

### Claim 1

A pharmaceutical composition comprising:
i) about 15 to about 25 wt.-% dexamethasone or a pharmaceutically acceptable salt or solvate thereof;
ii) about 45 to about 60 wt.-% filler;
iii) about 10 to about 30 wt.-% binder;
iv) about 2 to about 10 wt.-% disintegrant; and
v) about 0.01 to about 5 wt.-% lubricant;
wherein presence of all components add to 100 wt.-%, and wherein the pharmaceutical composition is prepared by wet granulation.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein the filler comprises lactose.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein the binder comprises starch, polyvinylpyrrolidone or a combination thereof.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein the disintegrant comprises sodium carboxymethyl starch.

### Claim 5 (depends on 1)

The pharmaceutical composition of claim 1, wherein the lubricant comprises magnesium stearate.

### Claim 6 (depends on 1)

The pharmaceutical composition of claim 1 in the form of a tablet.

### Claim 7 (depends on 6)

The pharmaceutical composition of claim 6 in the form of an uncoated tablet.

### Claim 8 (depends on 1)

The pharmaceutical composition of claim 1 formulated into a unit dosage form suitable for oral administration.

### Claim 9 (depends on 8)

The pharmaceutical composition of claim 8, wherein the unit dosage form comprises 20 mg of dexamethasone.

### Claim 10 (depends on 1)

A process for preparing the pharmaceutical composition of claim 1, the process comprising:
i) wet granulating dexamethasone or a pharmaceutically acceptable salt or solvate thereof, a binder, a filler, and a disintegrant to obtain a wet granulate;
ii) drying the wet granulate of step (i) to obtain a dry granulate having a Loss on Drying (LOD) % of about 1.5% to about 5%; and
iii) admixing the dry granulate of step (ii) with a lubricant to obtain a pharmaceutical composition.

### Claim 11 (depends on 10)

The process of claim 10, wherein step (i) comprises:
ia) dry mixing dexamethasone or a pharmaceutically acceptable salt or solvate thereof, a binder, a filler, and a disintegrant to obtain a dry mixture; and
ib) spraying the thus obtained dry mixture with a granulation solution or suspension to obtain a wet granulate.

### Claim 12 (depends on 10)

The process of claim 10, further comprising the step of:
iv) compressing the pharmaceutical composition of step iii) to obtain a tablet or a caplet.

### Claim 13 (depends on 10)

A pharmaceutical composition prepared by the process of claim 10.

### Claim 14 (depends on 1)

A method of treating multiple myeloma in a subject in need thereof comprising administering to the subject the pharmaceutical composition of claim 1 in combination with an anti-cancer drug.

### Claim 15 (depends on 14)

The method of claim 14, wherein the anti-cancer drug is thalidomide.

### Claim 16

An uncoated tablet comprising:
i) about 15 to about 25 wt.-% dexamethasone or a pharmaceutically acceptable salt or solvate thereof;
ii) about 45 to about 60 wt.-% filler;
iii) about 10 to about 30 wt.-% binder;
iv) about 2 to about 10 wt.-% disintegrant; and
v) about 0.01 to about 5 wt.-% lubricant;
wherein presence of all components add to 100 wt.-%, and wherein the uncoated tablet is prepared by wet granulation.

### Claim 17 (depends on 16)

The uncoated tablet of claim 16, wherein the filler comprises lactose.

### Claim 18 (depends on 16)

The uncoated tablet of claim 16, wherein the binder comprises starch, polyvinylpyrrolidone or a combination thereof.

### Claim 19 (depends on 16)

The uncoated tablet of claim 16, wherein the disintegrant comprises sodium carboxymethyl starch.

### Claim 20 (depends on 16)

The uncoated tablet of claim 16, wherein the lubricant comprises magnesium stearate.

### Claim 21 (depends on 16)

The uncoated tablet of claim 16 comprising 20 mg of dexamethasone.

### Claim 22 (depends on 16)

A process for preparing the uncoated tablet of claim 16, the process comprising:
i) wet granulating dexamethasone or a pharmaceutically acceptable salt or solvate thereof, a binder, a filler, and a disintegrant to obtain a wet granulate;
ii) drying the wet granulate of step (i) to obtain a dry granulate having a Loss on Drying (LOD) % of about 1.5% to about 5%;
iii) admixing the dry granulate of step (ii) with a lubricant to obtain a pharmaceutical composition; and
iv) compressing the pharmaceutical composition of step iii) to obtain an uncoated tablet.

### Claim 23 (depends on 22)

The process of claim 22, wherein step (i) comprises:
ia) dry mixing dexamethasone or a pharmaceutically acceptable salt or solvate thereof, a binder, a filler, and a disintegrant to obtain a dry mixture; and
ib) spraying the thus obtained dry mixture with a granulation solution or suspension to obtain a wet granulate.

### Claim 24 (depends on 22)

An uncoated tablet prepared by the process of claim 22.

### Claim 25 (depends on 16)

A method of treating multiple myeloma in a subject in need thereof comprising administering to the subject the uncoated tablet of claim 16 in combination with an anti-cancer drug.

### Claim 26 (depends on 25)

The method of claim 25, wherein the anti-cancer drug is thalidomide.

### Claim 27 (depends on 2)

The pharmaceutical composition of claim 2, wherein the filler comprises lactose monohydrate.

### Claim 28 (depends on 17)

The uncoated tablet of claim 17, wherein the filler comprises lactose monohydrate.