Opioid receptor modulator dosage formulations

• US 10,188,632 B2
• Filed: 05/05/2017
• Issued: 01/29/2019
• Est. Priority Date: 03/14/2013
• Status: Active Grant

• Current Assignee: Allergan Holdings Unlimited Company (Abbvie Incorporated)
• Original Assignee: Allergan Holdings Unlimited Company (Abbvie Incorporated)
• Inventors: Costello, Tim, Ceulemans, Jens Jozef, Jans, Eugeen Maria Jozef, Heyns, Philip Erna H.
• Primary Examiner(s): Stevens, Mark V
• Application Number:
  US15/588,304
• Publication Number:
  US 20170304268A1
• Time in Patent Office: 634 Days
• CPC Class Codes: A61K 31/4174 Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2004 Excipients; Inactive ingredients
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/501 Inorganic compounds
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

Abuse deterrent solid dosage formulations containing 5-({[2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid, and processes for the preparation and administration of these formulations.

Claims

1. A solid pharmaceutical dosage formulation comprising about 20 mg/dose to about 200 mg/dose of 5-({[2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid, about 60-80% by weight of silicified microcrystalline cellulose, about 0.55-0.95% by weight of colloidal silicon dioxide, about 3-7% by weight of crospovidone, about 5-15% mannitol, and about 0.55-0.95% by weight of magnesium stearate,

wherein extraction of the formulation with water or saline at 25°

C. for up to 12 hours produces a concentration of 5-({[2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid of less than or approximately 4 mg/ml.

2. The solid pharmaceutical dosage formulation of claim 1, formulated as a tablet or as a capsule.

3. The solid pharmaceutical dosage formulation of claim 1, further comprising a coating selected from a sugar coating, a gelatin coating, a film coating, and an enteric coating.

4. The solid pharmaceutical dosage formulation of claim 3, comprising about 75 mg to about 200 mg of 5-({[2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid.

5. The solid pharmaceutical dosage formulation of claim 3, comprising about 75 mg of 5-({[2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid.

6. The solid pharmaceutical dosage formulation of claim 3, comprising about 100 mg of 5-({[2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid.

7. The solid pharmaceutical dosage formulation of claim 1, wherein the formulation is substantially or completely free of naloxone.

8. The solid pharmaceutical dosage formulation of claim 1, wherein the formulation comprises:

about 65-75% by weight of silicified microcrystalline cellulose,

about 0.65-0.85% by weight of colloidal silica,

about 7.5-12.5% by weight of mannitol,

from about 4-6% by weight of crospovidone, and

from about 0.65-0.85% by weight of magnesium stearate.

9. The solid pharmaceutical dosage formulation of claim 1, wherein the formulation comprises

about 71% by weight of silicified microcrystalline cellulose,

about 0.75% by weight of colloidal silica,

about 10% by weight of mannitol,

about 5% by weight of crospovidone, and

about 0.75% by weight of magnesium stearate.

10. The solid pharmaceutical dosage formulation of claim 1, comprising a film coating present at about 2-4% by weight of the pharmaceutical composition.

11. The pharmaceutical composition of claim 10, wherein the film coating is present at about 3% by weight of the pharmaceutical composition.

12. The pharmaceutical composition of claim 10, wherein the film coating is a polyvinyl alcohol (PVA) based film coating.

13. The pharmaceutical composition of claim 1, further comprising at least one inert pharmaceutical excipient selected from a pharmaceutically acceptable dissolution-rate-modifying agent, a pharmaceutically acceptable plasticizer, a pharmaceutically acceptable coloring agent, a pharmaceutically acceptable opacifier, pharmaceutically acceptable anti-oxidant, a pharmaceutically acceptable preservative, a flavorant, a neutralizing agent, a buffering agent and combinations thereof.

14. A pharmaceutical composition comprising:

about 75 mg of 5-({[2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid;

about 426 mg of silicified microcrystalline cellulose;

about 4.5 mg of colloidal silica;

about 60 mg of mannitol;

about 30 mg of crospovidone; and

about 4.5 mg by weight of magnesium stearate;

wherein extraction of the composition with water or saline at 25oC for up to 12 hours produces a concentration of 5-({[2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid of less than or approximately 4 mg/ml.

15. A pharmaceutical composition comprising:

about 100 mg of 5-({[2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid;

about 568 mg of silicified microcrystalline cellulose;

about 6 mg of colloidal silica;

about 80 mg of mannitol;

about 40 mg of crospovidone; and

about 6 mg by weight of magnesium stearate;

wherein extraction of the composition with water or saline at 25oC for up to 12 hours produces a concentration of 5-({[2-Amino-3 -(4-carbamoyl-2, 6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid of less than or approximately 4 mg/ml.