Formulation of meloxicam

• US 9,808,468 B2
• Filed: 05/15/2017
• Issued: 11/07/2017
• Est. Priority Date: 06/09/2014
• Status: Active Grant

• Current Assignee: Iceutica Pty Limited (Assertio Holdings, Inc.)
• Original Assignee: Iceutica Pty Limited (Assertio Holdings, Inc.)
• Inventors: Bosch, H. William
• Primary Examiner(s): Barham, Bethany
• Assistant Examiner(s): FRAZIER, BARBARA S
• Application Number:
  US15/595,446
• Publication Number:
  US 20170246178A1
• Time in Patent Office: 176 Days
• Field of Search: None
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]

Abstract

Unit dosage forms of meloxicam containing either 5 mg or 10 mg of meloxicam that provide effective pain relief and have desirable pharmacokinetic properties are described. The unit dosage forms can provide pain relief when a single unit dose is administered to a patient and useful for treating pain such as osteoarthritis pain at a relatively low systemic exposure to meloxicam.

Claims

1. A method for treating osteoarthritis comprising administering a capsule form of a pharmaceutical composition comprising 5 mg of meloxicam having a median particle size, on a volume basis, between 100 nm and 1000 nm, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma AUC (0-∞

) of 7500-20000 h*ng/ml and a mean plasma Cmax of 350-950 ng/ml, wherein the D(0.9) of the particles of meloxicam is less than 4000 nm and greater than 1200 nm, and wherein the dissolution rate is such that, when tested using USP Apparatus 1 (baskets) set to rotation speed of 100 RPM in 500 mL of pH 6.1 phosphate buffer with 0.1% sodium lauryl sulfate (SLS) at 37°

C.±

0.5°

C., at least 80% of the meloxicam dissolves in 10 minutes or less.

2. The method of claim 1, wherein the dissolution rate is such that, when tested using USP Apparatus 1 (baskets) set to rotation speed of 100 RPM in 500 mL of pH 6.1 phosphate buffer with 0.1% sodium lauryl sulfate (SLS) at 37°

C.±

0.5°

C., at least 90% of the meloxicam dissolves in a time period selected from;

8 minutes or less;

7 minutes or less;

6 minutes or less; and

5 minutes or less.

3. The method of claim 1, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a median plasma Tmax of 1 to 3 hrs.

4. The method of claim 2, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a median plasma Tmax of 1 to 3 hrs.

5. The method of claim 1, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma AUC (0-∞

) that is 80% to 125% of 13610 ng-h/ml.

6. The method of claim 2, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma AUC (0-∞

) that is 80% to 125% of 13610 ng-h/ml.

7. The method of claim 1, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma Cmax that is 80% to 125% of 1253 ng/ml.

8. The method of claim 2, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma Cmax that is 80% to 125% of 1253 ng/ml.

9. A method for treating osteoarthritis comprising administering a capsule form of a pharmaceutical composition comprising 10 mg of meloxicam having a median particle size, on a volume basis, between 100 nm and 1000 nm, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma AUC (0-∞

) of 16000-44000 h*ng/ml and a mean blood plasma Cmax of 700-1900 ng/ml, wherein the D(0.9) of the particles of meloxicam is less than 4000 nm and greater than 1200 nm, and wherein the dissolution rate is such that, when tested using USP Apparatus 1 (baskets) set to rotation speed of 100 RPM in 1000 mL of pH 6.1 phosphate buffer with 0.1% sodium lauryl sulfate (SLS) at 37°

C.±

0.5°

C., at least 80% of the meloxicam dissolves in 15 minutes or less.

10. The method of claim 9 wherein the dissolution rate is such that, when tested using USP Apparatus 1 (baskets) set to rotation speed of 100 RPM in 1000 mL of pH 6.1 phosphate buffer with 0.1% sodium lauryl sulfate (SLS) at 37°

C.±

0.5°

C., at least 90% of the meloxicam dissolves in a time period selected from;

14 minutes or less;

13 minutes or less;

12 minutes or less;

11 minutes or less;

10 minutes or less; and

5 minutes or less.

11. The method of claim 9, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a median plasma Tmax of 1 to 3 hrs.

12. The method of claim 10, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a median plasma Tmax of 1 to 3 hrs.

13. The method of claim 9, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma AUC (0-∞

) that is 80% to 125% of 29,173 ng-h/ml.

14. The method of claim 10, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma AUC (0-∞

) that is 80% to 125% of 29,173 ng-h/ml.

15. The method of claim 9, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma Cmax that is 80% to 125% of 1253 ng/ml.

16. The method of claim 10, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma Cmax that is 80% to 125% of 1253 ng/ml.

17. A method for treating osteoarthritis comprising administering a capsule form of a pharmaceutical composition comprising 10 mg of meloxicam having a median particle size, on a volume basis, between 100 nm and 1000 nm, wherein a single dose, upon oral administration to a population of healthy adults in the fed state, provides a mean plasma Cmax of 525-1500 ng/ml and a mean plasma AUC (0-∞

) of 15000-42000 h*ng/ml, wherein the D(0.9) of the particles of meloxicam is less than 4000 nm and greater than 1200 nm, and wherein the dissolution rate is such that, when tested using USP Apparatus 1 (baskets) set to rotation speed of 100 RPM in 1000 mL of pH 6.1 phosphate buffer with 0.1% sodium lauryl sulfate (SLS) at 37°

C.±

0.5°

C., at least 80% of the meloxicam dissolves in 15 minutes or less.

18. The method of claim 17, wherein the dissolution rate is such that, when tested using USP Apparatus 1 (baskets) set to rotation speed of 100 RPM in 1000 mL of pH 6.1 phosphate buffer with 0.1% sodium lauryl sulfate (SLS) at 37°

C.±

0.5°

C., at least 90% of the meloxicam dissolves in a time period selected from;

14 minutes or less;

13 minutes or less;

12 minutes or less;

11 minutes or less;

10 minutes or less; and

5 minutes or less.

19. The method of claim 17, wherein a single dose, upon oral administration to a population of healthy adults in the fed state, provides a median plasma Tmax of 3 to 7 hrs.

20. The method of claim 18, wherein a single dose, upon oral administration to a population of healthy adults in the fed state, provides a median plasma Tmax of 3 to 7 hrs.

21. The method of claim 17, wherein a single dose, upon oral administration to a population of healthy adults in the fed state, provides a mean plasma Cmax that is 80% to 125% of 974 ng/ml.

22. The method of claim 18, wherein a single dose, upon oral administration to a population of healthy adults in the fed state, provides a mean plasma Cmax that is 80% to 125% of 974 ng/ml.

23. The method of claim 17, wherein a single dose, upon oral administration to a population of healthy adults in the fed state, provides a mean plasma AUC(0-∞

) that is 80% to 125% of 27,146 ng/ml.

24. The method of claim 18, wherein a single dose, upon oral administration to a population of healthy adults in the fed state, provides a mean plasma AUC(0-∞

) that is 80% to 125% of 27,146 ng/ml.