# US 11,896,586 B2 · Apixaban formulations

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- Number: US 11,896,586 B2
- Document ID: US11896586B2
- Status: Granted
- Kind: B2
- Application number: 17/047,428
- Filed: 2019-04-15
- Published: 2021-05-20
- Granted: 2024-02-13
- Earliest claimed: 2018-04-16
- Assignees: Bristol-Myers Squibb Company; Pfizer Inc.
- Applicants: Bristol-Myers Squibb Company; Pfizer Inc.
- Inventors: Sherif Ibrahim Farag Badawy; Timothy D. Stevens; Daniel Kuntz; Brett Waybrant
- Web page: https://patentgrep.com/patent/US11896586B2

## CPC

- A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A61K 9/0095: {Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006)}
- A61K 9/1623: {Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules}
- A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)}
- A61K 9/1676: {having a drug-free core with discrete complete coating layer containing drug (adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921)}
- A61K 9/4808: {characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release (capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084)}
- A61K 9/4816: {Wall or shell material}
- A61K 9/4825: {Proteins, e.g. gelatin (gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816)}
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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

Apixaban pharmaceutical formulation is provided. Also provided is a use of the apixaban formulation in treatment of a thromboembolic disorder.

## Claims

### Claim 1

A treated core comprising:
a core substrate; and
apixaban and a carrier on the core substrate,
wherein the treated core comprises from about 0.001% w/w to about 0.20% w/w apixaban, and
wherein the apixaban and the carrier are in a layer formed on a surface of the core substrate.

### Claim 2 (depends on 1)

The treated core of claim 1, wherein the apixaban and the carrier are applied to the surface of the core substrate by a spray-layered dispersion.

### Claim 3 (depends on 1)

The treated core of claim 1, wherein the core substrate is a sugar bead or sphere, or a microcrystalline cellulose, lactose, or mannitol particle.

### Claim 4 (depends on 1)

The treated core of claim 1, wherein the core substrate is a sugar bead or sphere.

### Claim 5 (depends on 4)

The treated core of claim 4, wherein the sugar bead or sphere comprises sugar syrup, corn starch, and/or sucrose.

### Claim 6 (depends on 1)

The treated core of claim 1, wherein the carrier is hydroxypropylcellulose and/or hypromellose.

### Claim 7 (depends on 1)

The treated core of claim 1, having a core size from about 150 microns to about 355 microns.

### Claim 8 (depends on 1)

A formulation comprising at least one said treated core of claim 1.

### Claim 9 (depends on 8)

The formulation of claim 8, which has an apixaban content from about 0.09% w/w to about 0.11% w/w.

### Claim 10 (depends on 8)

The formulation of claim 8, which has a carrier content from about 9% w/w to about 11% w/w.

### Claim 11 (depends on 8)

The formulation of claim 8, which has a core substrate content from about 89% w/w to about 91% w/w.

### Claim 12 (depends on 8)

The formulation of claim 8, which has an apixaban content of about 0.1% w/w.

### Claim 13 (depends on 8)

The formulation of claim 8, wherein the at least one said treated core is in a capsule.

### Claim 14 (depends on 13)

The formulation of claim 13, wherein the capsule is a gelatin capsule or an HPMC capsule.

### Claim 15 (depends on 13)

The formulation of claim 13, wherein the capsule is a sprinkle capsule.

### Claim 16 (depends on 13)

The formulation of claim 13, wherein the capsule comprises about 0.1 mg apixaban.

### Claim 17 (depends on 1)

A method of treating a thromboembolic disorder in a subject in need thereof comprising:
dispersing and/or dissolving at least one said treated core of claim 1 in a liquid carrier; and
administering the liquid carrier to the subject.

### Claim 18 (depends on 17)

The method of claim 17, wherein the liquid carrier is a food or beverage.

### Claim 19 (depends on 17)

The method of claim 17, wherein the subject is a neonate.

### Claim 20 (depends on 8)

The formulation according to claim 8,
wherein the formulation comprises about 0.1 mg to about 0.4 mg of apixaban.

### Claim 21 (depends on 20)

The formulation of claim 20, which has a carrier content from about 9% w/w to about 11% w/w.

### Claim 22 (depends on 20)

The formulation of claim 20, which has a core substrate content from about 89% w/w to about 91% w/w.

### Claim 23 (depends on 20)

The formulation of claim 20, which has an apixaban content of about 0.1% w/w to about 0.4% w/w.

### Claim 24 (depends on 20)

The formulation of claim 20, wherein the formulation comprises about 0.1 mg of apixaban.

### Claim 25 (depends on 20)

The formulation of claim 20, wherein the formulation comprises about 0.2 mg of apixaban.

### Claim 26 (depends on 20)

The formulation of claim 20, wherein the formulation comprises about 0.3 mg of apixaban.

### Claim 27 (depends on 20)

The formulation of claim 20, wherein the formulation comprises about 0.4 mg of apixaban.

### Claim 28 (depends on 20)

The formulation of claim 20, wherein the at least one treated core is in a capsule.

### Claim 29 (depends on 28)

The formulation of claim 28, wherein the capsule is a sprinkle capsule.

### Claim 30

A treated core comprising:
a core substrate; and
apixaban and a carrier on the core substrate,
wherein the treated core comprises from about 0.001% w/w to about 0.20% w/w apixaban,
wherein the apixaban and the carrier are in a layer formed on a surface of the core substrate, and
wherein the apixaban and the carrier are applied to the surface of the core substrate by a spray-layered dispersion process carried out with a concentration of apixaban in a solvent below a solubility limit.

### Claim 31 (depends on 30)

The treated core of claim 30, wherein the core substrate is a sugar bead or sphere, or a microcrystalline cellulose, lactose, or mannitol particle.

### Claim 32 (depends on 30)

The treated core of claim 30, having a core size from about 150 microns to about 355 microns.

### Claim 33 (depends on 30)

A formulation comprising at least one said treated core of claim 30.

### Claim 34 (depends on 33)

The formulation of claim 33, which has an apixaban content from about 0.09% w/w to about 0.11% w/w.

### Claim 35 (depends on 33)

The formulation of claim 33, which has a carrier content from about 9% w/w to about 11% w/w.

### Claim 36 (depends on 33)

The formulation of claim 33, which has a core substrate content from about 89% w/w to about 91% w/w.

### Claim 37 (depends on 30)

A method of treating a thromboembolic disorder in a subject in need thereof comprising:
dispersing and/or dissolving at least one said treated core of claim 30 in a liquid carrier; and
administering the liquid carrier to the subject.

### Claim 38 (depends on 37)

The method of claim 37, wherein the liquid carrier is a food or beverage.

### Claim 39 (depends on 33)

The formulation according to claim 33, wherein the formulation comprises about 0.1 mg to about 0.4 mg of apixaban.

### Claim 40 (depends on 33)

The formulation of claim 33, wherein the formulation comprises about 0.1 mg of apixaban.

### Claim 41 (depends on 33)

The formulation of claim 33, wherein the formulation comprises about 0.2 mg of apixaban.

### Claim 42 (depends on 33)

The formulation of claim 33, wherein the formulation comprises about 0.3 mg of apixaban.

### Claim 43 (depends on 33)

The formulation of claim 33, wherein the formulation comprises about 0.4 mg of apixaban.

### Claim 44 (depends on 39)

The formulation of claim 39, wherein the at least one treated core is in a capsule.

### Claim 45 (depends on 44)

The formulation of claim 44, wherein the capsule is a sprinkle capsule.