# US 11,433,072 B1 · Oral dosage forms of ibrutinib

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- Number: US 11,433,072 B1
- Document ID: US11433072B1
- Status: Granted
- Kind: B1
- Application number: 17/343,900
- Filed: 2021-06-10
- Granted: 2022-09-06
- Earliest claimed: 2021-06-10
- Assignees: Hikma Pharmaceuticals USA Inc.
- Applicants: Hikma Pharmaceuticals USA Inc.
- Inventors: Mahmoud Ghannam; Shahin Fesharaki; Mohammad Al Hreebat; Ahmad Arif Mohammad
- Web page: https://patentgrep.com/patent/US11433072B1

## CPC

- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/4858: {Organic compounds}
- A61K 9/4866: {Organic macromolecular compounds}
- 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)

## Abstract

Stable and bioavailable oral dosage forms of ibrutinib, the dosage forms comprising ibrutinib and an acidifying agent. The dosage forms can further comprise a binder, such as sodium alginate, a surfactant, a lubricant, a filler and/or a disintegrant. Methods of treating cancers, particularly blood cancers, and graft versus host disease comprising administering to a patient in need thereof a dosage form comprising ibrutinib and an acidifying agent.

## Claims

### Claim 1

A solid oral dosage formulation comprising ibrutinib and an acidifying agent, wherein the ibrutinib has a particle size d90 of from about 75 to about 105 microns, and wherein the oral dosage formulation releases about 70% or more of the ibrutinib within about 45 minutes when measured in either 900 mL of 3.0% w/v Polysorbate 20 in 50 mM phosphate buffer, pH 6.8, paddles at 75 rpm or 900 mL of 0.1 N HCl, paddles at 50 rpm.

### Claim 2 (depends on 1)

The oral dosage formulation of claim 1, wherein the acidifying agent is present in an amount of from about 0.5 to about 5.0 weight percent.

### Claim 3 (depends on 2)

The oral dosage formulation of claim 2, wherein the acidifying agent is present in an amount of from about 1.0 to about 3.0 weight percent.

### Claim 4 (depends on 1)

The oral dosage formulation of claim 1, wherein the acidifying agent is selected from the group consisting of tartaric acid and citric acid.

### Claim 5 (depends on 4)

The oral dosage formulation of claim 4, wherein the acidifying agent is tartaric acid.

### Claim 6 (depends on 1)

The oral dosage formulation of claim 1, further comprising a binder.

### Claim 7 (depends on 6)

The oral dosage formulation of claim 6, wherein the binder is present in an amount of from about 0.5 to about 10.0 weight percent.

### Claim 8 (depends on 7)

The oral dosage formulation of claim 7, wherein the binder is present in an amount of from about 1.0 to about 5.0 weight percent.

### Claim 9 (depends on 6)

The oral dosage formulation of claim 6, wherein the binder comprises sodium alginate.

### Claim 10 (depends on 1)

The oral dosage formulation of claim 1, wherein the ibrutinib is Form I ibrutinib.

### Claim 11 (depends on 1)

The oral dosage formulation of claim 1, wherein the oral dosage form is a capsule.

### Claim 12 (depends on 1)

The oral dosage formulation of claim 1, wherein the oral dosage form releases about 90% or more of the ibrutinib within about 45 minutes.

### Claim 13 (depends on 1)

A method of treating a cancer by administering to a patient in need thereof the oral dosage formulation of claim 1.

### Claim 14 (depends on 1)

A method of treating a graft versus host disease by administering to a patient in need thereof the oral dosage formulation of claim 1.

### Claim 15

A solid oral dosage formulation comprising ibrutinib having a particle size d90 of from about 75 to about 105 microns, an acidifying agent present in an amount of about 1.0 to about 5.0 weight percent, a binder present in an amount of from about 1.0 to about 10 weight percent, and an ionic surfactant present in an amount of from about 0.1 to about 2 weight percent, wherein the oral dosage formulation releases about 70% or more of the ibrutinib within about 45 minutes when measured in either 900 mL of 3.0% w/v Polysorbate 20 in 50 mM phosphate buffer, pH 6.8, paddles at 75 rpm or 900 mL of 0.1 N HCl, paddles at 50 rpm.

### Claim 16 (depends on 15)

The oral dosage formulation of claim 15, wherein the acidifying agent is selected from tartaric acid and citric acid, and wherein the binder is sodium alginate, and wherein the surfactant is sodium lauryl sulfate.

### Claim 17 (depends on 15)

The oral dosage formulation of claim 15, further comprising one or more of a lubricant, a filler, and/or a disintegrant.

### Claim 18

A solid oral dosage formulation consisting essentially of ibrutinib, an acidifying agent, a binder, an ionic surfactant, a lubricant, a filler, and a disintegrant, wherein the ibrutinib has a particle size d90 of from about 75 to about 105 microns, and wherein the dosage formulation releases about 70% or more of the ibrutinib within about 45 minutes when tested in either 900 mL of 3.0% w/v Polysorbate 20 in 50 mM phosphate buffer, pH 6.8, paddles at 75 rpm or 900 mL of 0.1 N HCl, paddles at 50 rpm.

### Claim 19 (depends on 18)

The oral dosage formulation of claim 18, wherein the acidifying agent is present in an amount of from about 1.0 weight percent to about 3.0 weight percent.

### Claim 20 (depends on 18)

The oral dosage formulation of claim 18, consisting essentially of ibrutinib, tartaric acid or citric acid, sodium alginate, sodium lauryl sulfate, magnesium stearate, a microcrystalline cellulose and croscarmellose sodium.

### Claim 21 (depends on 20)

The oral dosage formulation of claim 20, wherein the tartaric acid or citric acid is present in an amount of from about 1.0 to about 3.0 weight percent.

### Claim 22 (depends on 20)

The oral dosage formulation of claim 20, wherein the sodium alginate is present in an amount of from about 1.0 to about 5.0 weight percent.

### Claim 23 (depends on 2)

The oral dosage form of claim 2, wherein the oral dosage formulation releases about 90% or more of the ibrutinib within about 45 minutes.

### Claim 24 (depends on 20)

The oral dosage form of claim 20, wherein the oral dosage formulation releases about 90% or more of the ibrutinib within about 45 minutes.

### Claim 25 (depends on 18)

The oral dosage formulation of claim 18 consisting of ibrutinib, an acidifying agent, a binder, a non-ionic surfactant, a lubricant, a filler, and a disintegrant.

### Claim 26 (depends on 25)

The oral dosage form of claim 25, wherein the oral dosage formulation releases about 90% or more of the ibrutinib within about 45 minutes.

### Claim 27 (depends on 25)

The oral dosage formulation of claim 25, consisting of ibrutinib, tartaric acid or citric acid, sodium alginate, sodium lauryl sulfate, magnesium stearate, a microcrystalline cellulose and croscarmellose sodium.

### Claim 28 (depends on 27)

The oral dosage form of claim 27, wherein the oral dosage formulation releases about 90% or more of the ibrutinib within about 45 minutes.