Opioid receptor modulator dosage formulations
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.
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.