APIXABAN FORMULATIONS

US 20130045245A1
Filed: 02/24/2011
Published: 02/21/2013
Est. Priority Date: 02/25/2010
Status: Active Grant

First Claim

Patent Images

1. A composition comprising crystalline apixaban particles having a mean particle size equal to or less than about 89 μ

m and a pharmaceutically acceptable diluent or carrier.

View all claims

2 Assignments

Timeline View

Assignment View

0 Petitions

Accused Products

Abstract

Compositions comprising crystalline apixaban particles having a D₉₀equal to or less than 89 μm, and a pharmaceutically acceptable carrier, are substantially bioequivalent and can be used to for the treatment and/or prophylaxis of thromboembolic disorders.

Citations

25 Claims

1. A composition comprising crystalline apixaban particles having a mean particle size equal to or less than about 89 μ
- m and a pharmaceutically acceptable diluent or carrier.
- View Dependent Claims (3, 4, 6, 7, 8, 9, 10, 11, 12, 13, 16, 17, 18)
- - 3. A composition as defined in claim 1, wherein said composition comprises Form N-1 of apixaban.
  - 4. A composition as defined in claim 1, wherein particles with a D₉₀equal to or less than 89 μ
    - m.
  - 6. A composition as defined in claim 1, wherein particles with a D₉₀equal to or less than 50 μ
    - m.
  - 7. A composition as defined in claim 1, wherein particles with a D₉₀equal to or less than 30 μ
    - m.
  - 8. A composition as defined in claim 1, wherein particles with a D₉₀equal to or less than 25 μ
    - m.
  - 9. A composition as defined in claim 1 which exhibits an AUC and/or C_maxthat is at least 80% of the mean AUC and/or C_maxobserved for an equivalent formulation differing only in that the apixaban mean particle size is 89 μ
    - m.
  - 10. A composition as defined in claim 1 which exhibits an AUC and/or C_maxthat is at least 80% of the mean AUC and/or C_maxobserved for an equivalent formulation differing only in that the apixaban mean particle size is 85 μ
    - m.
  - 11. A composition as defined in claim 1, further comprising:
    - from 1% to 2% by weight of a surfactant.
  - 12. A composition as defined in claim 11, wherein the surfactant is sodium lauryl sulfate.
  - 13. A method for the treatment or prophylaxis of a thromboembolic disorder, comprising administering to a patient in need of such treatment or prophylaxis a therapeutically effective amount of a composition as defined in claim 1.
  - 16. A process of manufacturing apixaban tablets having a composition as defined in claim 1, comprising the steps of:
    - (1) blending raw materials prior to granulation;
      
      (2) granulating the raw materials from the step (1) using a wet or dry granulation process;
      
      (3) blending the granules obtained in the step (2) with extragranular raw materials;
      
      (4) compressing the blend from the step (3) into tablets; and
      
      (5) film coating the tablets from the step (4).
  - 17. A process of manufacturing apixaban tablets having a composition as defined in claim 1, comprising the steps of:
    - (1) blending raw materials with apixaban of controlled particle size to form a mix;
      
      (2) adding intragranular portions of a binder, a disintegrant and at least one filler to the mix from the step (1) to form a blend;
      
      (3) granulating the materials from the step (2) using a dry granulation process or a wet granulation process,wherein the dry granulation process comprises;
      
      delumping an intragranular lubricant using a screen or mill;
      
      adding the intragranular lubricant to the blend from the step (2) and blending to form a lubricated blend;
      
      compacting the lubricated blend to ribbons of density in a range of 1.1 to 1.2 g/cc and sizing the compacted ribbons using a roller compactor, andwherein the wet granulation process comprises;
      
      wet granulating the blend from the step (2) using water to a target end point and, optionally, sizing the wet-granules by passing through a screen or mill;
      
      removing the water from the granulation by drying in a convection oven or a fluid-bed dryer; and
      
      sizing the dried granules by passing through a screen or mill;
      
      (4) blending the granules obtained in the step (3) and an extragranular disintegrant in a blender;
      
      (5) delumping an extragranular lubricant using a screen or mill and blending with granules from the step (4);
      
      (6) compressing the blend from the step (5) into tablets; and
      
      (7) film coating the tablets from the step (6).
  - 18. A process of manufacturing apixaban tablets according to claim 17, wherein the dry granulation process is used.

2. A composition comprising crystalline apixaban particles having a mean particle size equal to or less than about 85 μ
- m and a pharmaceutically acceptable diluent or carrier.
- View Dependent Claims (5, 19, 20, 21, 22, 23, 24, 25)
- - 5. A composition as defined in claim 2, wherein particles with a D₉₀equal to or less than 85 μ
    - m.
  - 19. A composition as defined in claim 2, wherein said composition comprises Form N-1 of apixaban.
  - 20. A composition as defined in claim 2, wherein particles with a D90 equal to or less than 50 μ
    - m.
  - 21. A composition as defined in claim 2, wherein particles with a D90 equal to or less than 30 μ
    - m.
  - 22. A composition as defined in claim 2, wherein particles with a D90 equal to or less than 25 μ
    - m.
  - 23. A composition as defined in claim 2, further comprising:
    - from 1% to 2% by weight of a surfactant.
  - 24. A composition as defined in claim 23, wherein the surfactant is sodium lauryl sulfate.
  - 25. A method for the treatment or prophylaxis of a thromboembolic disorder, comprising administering to a patient in need of such treatment or prophylaxis a therapeutically effective amount of a composition as defined in claim 2.

14-15. -15. (canceled)

Specification

Resources

Litigation Campaign Assessment

Current Assignee
Bristol-Myers Squibb Company, Pfizer Inc.
Original Assignee
Bristol-Myers Squibb Company, Pfizer Inc.
Inventors
Patel, Jatin, Frost, Charles, Jia, Jingpin, Vemavarapu, Chandra

Granted Patent

US 9,326,945 B2
Time in Patent Office

Days
Field of Search
US Class Current

424/400
CPC Class Codes

A61K 31/4162   condensed with heterocyclic...

A61K 31/437   the heterocyclic ring syste...

A61K 31/4412   having oxo groups directly ...

A61K 31/4545   containing a six-membered r...

A61K 9/14   Particulate form, e.g. powd...

A61K 9/16   Agglomerates; Granulates; M...

A61K 9/20   Pills, tablets, discs, rods...

A61K 9/2013   Organic compounds, e.g. pho...

A61K 9/2018   Sugars, or sugar alcohols, ...

A61K 9/2054   Cellulose; Cellulose deriva...

A61K 9/2095   Tabletting processes; Dosag...

A61K 9/48   Preparations in capsules, e...

A61K 9/4833   Encapsulating processes; Fi...

A61P 1/00   Drugs for disorders of the ...

A61P 7/02   Antithrombotic agents; Anti...

APIXABAN FORMULATIONS

First Claim

2 Assignments

0 Petitions

Accused Products

Abstract

Citations

25 Claims

Specification

Solutions

Use Cases

Quick Links

APIXABAN FORMULATIONS

First Claim

2 Assignments

Subscription Required

Subscription Required

0 Petitions

Subscription Required

Accused Products

Subscription Required

Abstract

Citations

25 Claims

Specification

Subscription Required

Solutions

Use Cases

Quick Links