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. An abuse deterrent, mono-phasic pharmaceutical composition suitable for single dose administration for treating a condition mediated by an opioid receptor consisting essentially of 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, from about 60-80% by weight of silicified microcrystalline cellulose, from about 0.55-0.95% by weight of colloidal silica, from about 5-15% by weight of mannitol, from about 3-7% by weight of crospovidone, from about 0.55-0.95% by weight of magnesium stearate, and a water-soluble, pH-independent film coating, wherein the 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 is present at about 5-20% by weight of the composition, and wherein extraction of the composition 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 abuse deterrent, mono-phasic pharmaceutical composition of claim 1 , wherein the composition consists essentially of 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, from about 65-75% by weight of silicified microcrystalline cellulose, from about 0.65-0.85% by weight of colloidal silica, from 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.
3. The abuse deterrent, mono-phasic pharmaceutical composition of claim 1 , wherein the composition consists essentially of 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 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.
4. The pharmaceutical composition of claim 1 , wherein the film coating is present at about 2-4% by weight of the pharmaceutical composition.
5. An abuse deterrent, mono-phasic pharmaceutical composition suitable for single dose administration for treating a condition mediated by an opioid receptor consisting essentially of:
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;
about 4.5 mg by weight of magnesium stearate; and a water-soluble, pH-independent film coating, wherein extraction of the composition 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.
6. The pharmaceutical composition of claim 5 , wherein the film coating is present at about 3% by weight of the pharmaceutical composition.
7. An abuse deterrent, mono-phasic pharmaceutical composition suitable for single dose administration for treating a condition mediated by an opioid receptor consisting essentially of:
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;
about 6 mg by weight of magnesium stearate; and a water-soluble, pH-independent film coating, wherein extraction of the composition 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.
8. The pharmaceutical composition of claim 7 , wherein the film coating is present at about 3% by weight of the pharmaceutical composition.
9. An abuse deterrent, mono-phasic pharmaceutical composition suitable for single dose administration for treating a condition mediated by an opioid receptor comprising:
about 100 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 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,
about 0.75% by weight of magnesium stearate, and a water-soluble, pH-independent film coating, wherein extraction of the composition 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.
10. The pharmaceutical composition of claim 9 , wherein the film coating is present at about 3% by weight of the pharmaceutical composition.
11. The pharmaceutical composition of claim 10 , wherein the film coating is a polyvinyl alcohol (PVA) based film coating.
12. An abuse deterrent, mono-phasic pharmaceutical composition suitable for single dose administration for treating a condition mediated by an opioid receptor 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, and a water-soluble, pH-independent film coating, wherein extraction of the composition 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.
13. The pharmaceutical compositions of claim 12 , wherein the film coating is present at about 3% by weight of the pharmaceutical composition.
14. The pharmaceutical composition of claim 13 , wherein the film coating is a polyvinyl alcohol (PVA) based film coating.
15. The pharmaceutical composition of claim 3 wherein the film coating is present at about 3% by weight of the pharmaceutical composition.
16. The pharmaceutical composition of claim 15 wherein the film coating is a polyvinyl alcohol (PVA) based film coating.
17. The pharmaceutical composition of claim 4 wherein the film coating is a polyvinyl alcohol (PVA) based film coating.