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-4,5-dihydro-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid, and processes for the preparation and administration of these formulations.
1 . A tablet comprising
about 75 mg of 5-({[(2S)-2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[(1S)-1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid,
silicified microcrystalline cellulose,
colloidal silicon dioxide,
crospovidone, and
mannitol.
2 . The tablet of claim 1 , wherein said tablet comprises about 60-80% by weight of silicified microcrystalline cellulose, about 0.55-0.95% by weight of colloidal silicon dioxide, crospovidone, and about 5-15% by weight of mannitol.
3 . The tablet of claim 1 , wherein said tablet comprises about 60-80% by weight of silicified microcrystalline cellulose, about 0.55-0.95% by weight of colloidal silicon dioxide, crospovidone, and about 10% by weight of mannitol.
4 . The tablet of claim 1 , comprising
about 1-20% by weight of mannitol.
5 . The tablet of claim 4 , comprising about 60-80% by weight of silicified microcrystalline cellulose.
6 . The tablet of claim 5 , comprising about 0.45-1.0% by of weight of colloidal silicon dioxide.
7 . The tablet of claim 6 , comprising about 5-15% by weight of mannitol.
8 . The tablet of claim 7 , comprising about 0.55-0.95% by weight of colloidal silicon dioxide.
9 . The tablet of claim 8 , comprising a lubricant.
10 . The tablet of claim 9 , wherein extraction of the tablet with water or saline at 25° C. for 12 hours results in a concentration of 5-({[(2S)-2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[(1S)-1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid of less than or approximately 4 mg/ml.
11 . The tablet of claim 9 , wherein extraction of the tablet at 25° C. for 12 hours in acidic solvent results in a greater concentration of 5-({[(2S)2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[(1S)-1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid than extraction of 5-({[2(S)-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[(1S)-1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid at 25° C. for 12 hours in water or saline.
12 . A tablet comprising
about 100 mg of 5-({[(2S)-2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[(1S)-1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid, silicified microcrystalline cellulose,
colloidal silicon dioxide,
crospovidone, and
mannitol.
13 . The tablet of claim 12 , wherein said tablet comprises about 60-80% by weight of silicified microcrystalline cellulose, about 0.55-0.95% by weight of colloidal silicon dioxide, crospovidone, and about 5-15% by weight of mannitol.
14 . The tablet of claim 12 , wherein said tablet comprises about 60-80% by weight of silicified microcrystalline cellulose, about 0.55-0.95% by weight of colloidal silicon dioxide, crospovidone, and about 10% by weight of mannitol.
15 . The tablet of claim 12 , comprising
about 1-20% by weight of mannitol.
16 . The tablet of claim 15 , comprising about 60-80% by weight of silicified microcrystalline cellulose.
17 . The tablet of claim 16 , comprising about 0.45-1.0% by of weight of colloidal silicon dioxide.
18 . The tablet of claim 17 , comprising about 5-15% by weight of mannitol.
19 . The tablet of claim 18 , comprising about 0.55-0.95% by weight of colloidal silicon dioxide.
20 . The tablet of claim 19 , comprising a lubricant.
21 . The tablet of claim 20 , wherein extraction of the tablet with water or saline at 25° C. for 12 hours results in a concentration of 5-({[(2S)-2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[(1S)-1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid of less than or approximately 4 mg/ml.
22 . The tablet of claim 20 , wherein extraction of the tablet at 25° C. for 12 hours in acidic solvent results in a greater concentration of 5-({[(2S)-2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[(1S)-1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid than extraction of 5-({[(2S)-2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[(1S)-1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid at 25° C. for 12 hours in water or saline.