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. An abuse-deterrent, mono-phasic pharmaceutical 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,
about 60-80% by weight silicified microcrystalline cellulose;
crospovidone;
about 5-15% by weight mannitol; and
optionally, a glidant and/or lubricant.
2. The tablet of claim 1 , 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.
3. The tablet of claim 1 , comprising about 65-75% by weight silicified microcrystalline cellulose, and about 7.5-12.5% by weight mannitol.
4. The tablet of claim 3 , comprising about 3-7% by weight crospovidone and a lubricant.
5. The tablet of claim 4 , wherein the lubricant is magnesium stearate present in an amount of about 0.55-0.95% by weight.
6. The tablet of claim 5 , 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;
about 390 mg-450 mg of silicified microcrystalline cellulose;
about 18 mg-42 mg crospovidone;
about 45 mg-75 mg of mannitol; and
about 3.3 mg-5.7 mg of magnesium stearate.
7. The tablet of claim 6 , 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;
about 390 mg-450 mg of silicified microcrystalline cellulose;
about 30 mg of crospovidone;
about 60 mg of mannitol; and
about 4.5 mg of magnesium stearate.
8. The tablet of claim 3 , comprising a glidant, wherein the glidant is colloidal silicon dioxide present in an amount of about 0.55-0.95% by weight.
9. The tablet of claim 8 , 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;
about 390 mg-450 mg of silicified microcrystalline cellulose;
crospovidone;
about 45 mg-75 mg of mannitol; and
about 3.3 mg-5.7 mg of colloidal silicon dioxide.
10. The tablet of claim 9 , 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;
about 390 mg-450 mg of silicified microcrystalline cellulose;
crospovidone;
about 60 mg of mannitol; and
about 4.5 mg of colloidal silicon dioxide.
11. The tablet of claim 3 , comprising about 3%-7% by weight crospovidone, a glidant and a lubricant.
12. An abuse-deterrent, mono-phasic pharmaceutical 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,
about 60-80% by weight silicified microcrystalline cellulose,
crospovidone,
about 5-15% by weight mannitol, and
optionally a glidant and/or a lubricant.
13. The tablet of claim 12 , 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.
14. The tablet of claim 12 , comprising about 65-75% by weight silicified microcrystalline cellulose, and about 7.5-12.5% by weight mannitol.
15. The tablet of claim 14 , comprising about 3-7% by weight crospovidone and a lubricant.
16. The tablet of claim 15 , wherein the lubricant is magnesium stearate present in an amount of about 0.55-0.95% by weight.
17. The tablet of claim 6 , 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;
about 520 mg-600 mg of silicified microcrystalline cellulose;
about 24 mg-56 mg crospovidone;
about 60 mg-100 mg of mannitol; and
about 4.4 mg-7.6 mg of magnesium stearate.
18. The tablet of claim 17 , 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;
about 520 mg-600 mg of silicified microcrystalline cellulose;
about 40 mg of crospovidone;
about 80 mg of mannitol; and
about 6 mg of magnesium stearate.
19. The tablet of claim 14 , comprising a glidant, wherein the glidant is colloidal silicon dioxide present in an amount of about 0.55-0.95% by weight.
20. The tablet of claim 19 , 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;
about 520 mg-600 mg of silicified microcrystalline cellulose;
crospovidone;
about 60 mg-100 mg of mannitol; and
about 4.4 mg-7.6 mg of colloidal silicon dioxide.
21. The tablet of claim 20 , 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;
about 520 mg-600 mg of silicified microcrystalline cellulose;
crospovidone;
about 80 mg of mannitol; and
about 6 mg of colloidal silicon dioxide.
22. The tablet of claim 14 , comprising about 3%-7% by weight crospovidone, a glidant and a lubricant.
23. The tablet of claim 22 , wherein the glidant is colloidal silicon dioxide and the lubricant is magnesium stearate.
24. The tablet of claim 23 , comprising:
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;
about 65-75% by weight silicified microcrystalline cellulose;
about 4-6% crospovidone;
about 7.5-12.5% by weight mannitol; and
colloidal silicon dioxide and magnesium stearate.
25. The tablet of claim 23 , 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;
about 520 mg-600 mg of silicified microcrystalline cellulose;
about 24 mg-56 mg of crospovidone;
about 60 mg-100 mg of mannitol; and
colloidal silicon dioxide and magnesium stearate.
26. The tablet of claim 25 , 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;
about 520 mg-600 mg of silicified microcrystalline cellulose;
about 40 mg of crospovidone;
about 80 mg of mannitol; and
colloidal silicon dioxide and magnesium stearate.
27. The tablet of claim 11 , wherein the glidant is colloidal silicon dioxide and the lubricant is magnesium stearate.
28. The tablet of claim 27 , comprising:
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;
about 65-75% by weight silicified microcrystalline cellulose;
about 4-6% crospovidone;
about 7.5-12.5% by weight mannitol; and
colloidal silicon dioxide and magnesium stearate.
29. The tablet of claim 27 , 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;
about 390 mg-450 mg of silicified microcrystalline cellulose;
about 18 mg-42 mg of crospovidone;
about 45 mg-75 mg of mannitol; and
colloidal silicon dioxide and magnesium stearate.
30. The tablet of claim 29 , 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;
about 390 mg-450 mg of silicified microcrystalline cellulose;
about 30 mg of crospovidone;
about 60 mg of mannitol; and
colloidal silicon dioxide and magnesium stearate.