Rapid dissolution formulation of a calcium receptor-active compound

• US 9,375,405 B2
• Filed: 11/09/2010
• Issued: 06/28/2016
• Est. Priority Date: 09/12/2003
• Status: Active Grant

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Lawrence, Glen Gary, Alvarez, Francisco J., Lin, Hung-Ren H., Ju, Tzuchi R.
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): SAMALA, JAGADISHWAR RAO
• Application Number:
  US12/942,646
• Publication Number:
  US 20110136915A1
• Time in Patent Office: 2,058 Days
• Field of Search: 514/275, 514/579, 514/607, 514/614, 514/646, 514/649, 424/434, 424/464, 424/465, 424/476, 424/490
• US Class Current: 1/1
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• CPC Class Codes: A61P 5/20 for decreasing, blocking or antagonising the activity of PTH

Abstract

The present invention relates to a pharmaceutical composition comprising a therapeutically effective amount of a calcium receptor-active compound and at least one pharmaceutically acceptable excipient, wherein the composition has a controlled dissolution profile. The present invention further relates to a method of manufacturing the pharmaceutical composition, as well as a method of treating a disease using the pharmaceutical composition.

Claims

1. A pharmaceutical composition comprising:

(a) from about 10% to about 40% by weight of cinacalcet HCl in an amount of from about 20 mg to about 100 mg;

(b) from about 45% to about 85% by weight of a diluent selected from the group consisting of microcrystalline cellulose, starch, dicalcium phosphate, lactose, sorbitol, mannitol, sucrose, methyl dextrins, and mixtures thereof,

(c) from about 1% to about 5% by weight of at least one binder selected from the group consisting of povidone, hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose, and mixtures thereof; and

(d) from about 1% to 10% by weight of at least one disintegrant selected from the group consisting of crospovidine, sodium starch glycolate, croscarmellose sodium, and mixtures thereof,

wherein the percentage by weight is relative to the total weight of the composition, and wherein the composition is for the treatment of at least one of hyperparathyroidism, hyperphosphonia, hypercalcemia, and elevated calcium phosphorus product.

2. The composition according to claim 1, further comprising at least one excipient selected from the group consisting of lubricants and clear and color coating materials.

3. The composition according to claim 1, further comprising from about 1% to about 6% by weight of at least one coating material selected from the group consisting of clear and color coating materials wherein the percentage by weight is relative to the total weight of the composition.

4. The composition according to claim 1, further comprising from about 0.05% to about 5% of at least one additive selected from the group consisting of glidants, lubricants and adherents, wherein the percentage by weight is relative to the total weight of the composition.

5. The composition according to claim 1, wherein the at least one binder is povidone.

6. The composition according to claim 1, wherein the at least one disintegrant is crospovidone.

7. The composition according to claim 6 wherein the form of the cinacalcet HCl is selected from the group consisting of needle-shape particles, rod-shape particles, plate-shaped particles, and mixtures thereof.

8. The composition according to claim 1, wherein the cinacalcet HCl is in a form selected from the group consisting of amorphous powders, crystalline particles, and mixtures thereof.

9. The composition according to claim 8 wherein the particle D₅₀ of the cinacalcet HCl particles is less than or equal to about 50 μ

m.

10. The composition according to claim 9, wherein the granules have a granule D₅₀ measured using a sieve analysis ranging from about 50 μ

m to about 150 μ

m.

11. The composition according to claim 9, wherein the granules have a granule D₅₀ measured using a sieve analysis ranging from about 80 μ

m to about 130 μ

m.

12. The composition according to claim 11, wherein the crospovidone is present intergranularly.

13. The composition according to claim 11, wherein the crospovidone is present intragranularly.

14. The composition according to claim 9, wherein the disintegrant is crospovidone and the crospovidone is present intergranularly, intragranularly, or a combination thereof.

15. The composition according to claim 1 wherein the composition comprises granules.

16. The composition according to claim 1 further comprising from about 0.05% to about 1.5% by weight of colloidal silicon dioxide relative to the total weight of the composition.

17. The composition according to claim 1 further comprising from about 0.05% to about 1.5% by weight of magnesium stearate relative to the total weight of the composition.

18. The composition according to claim 1, wherein the hyperparathyroidism is primary hyperparathyroidism or secondary hyperparathyroidism.

19. The composition according to claim 1, wherein the diluent is microcrystalline cellulose or starch.

20. A pharmaceutical composition comprising:

(a) from about 10% to about 40% by weight of cinacalcet HCl in an amount of from about 20 mg to about 100 mg;

(b) from about 45% to about 85% by weight of a diluent selected from the group consisting of microcrystalline cellulose, starch, dicalcium phosphate, lactose, sorbitol, mannitol, sucrose, methyl dextrins, and mixtures thereof,

(c) from about 1% to about 5% by weight of at least one binder selected from the group consisting of povidone, hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose, and mixtures thereof; and

(d) from about 1% to 10% by weight of at least one disintegrant selected from the group consisting of crospovidine, sodium starch glycolate, croscarmellose sodium, and mixtures thereof,

wherein the disintegrant is at least present intragranularly and wherein the composition is for the treatment of at least one of hyperparathyroidism, hyperphosphonia, hypercalcemia, and elevated calcium phosphorus product.

21. A pharmaceutical composition comprising:

(a) from about 10% to about 40% by weight of cinacalcet HCl in an amount of from about 20 mg to about 100 mg;

(b) from about 5% to about 10% by weight of starch;

(b) from about 40% to about 75% by weight of microcrystalline cellulose,

(c) from about 1% to about 5% by weight of povidone, and

(d) from about 1% to 10% by weight of crospovidone,

wherein the percentage by weight is relative to the total weight of the composition, and wherein the composition is for the treatment of at least one of hyperparathyroidism, hyperphosphonia, hypercalcemia, and elevated calcium phosphorus product.

22. The composition according to claim 21 further comprising from about 0.05% to about 1.5% by weight of colloidal silicon dioxide relative to the total weight of the composition.

23. The composition according to claim 21 further comprising from about 0.05% to about 1.5% by weight of magnesium stearate relative to the total weight of the composition.