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 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; and
about 5-15% by weight mannitol.
2. The tablet of claim 1 , comprising about 65-75% by weight silicified microcrystalline cellulose, and about 7.5-12.5% by weight mannitol.
3. The tablet of claim 2 , comprising about 3-7% by weight crospovidone and further comprising a lubricant.
4. The tablet of claim 3 , wherein the lubricant is magnesium stearate present in an amount of about 0.55-0.95% by weight.
5. The tablet of claim 4 , 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.
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 30 mg of crospovidone;
about 60 mg of mannitol; and
about 4.5 mg of magnesium stearate.
7. The tablet of claim 2 , further comprising a glidant, wherein the glidant is colloidal silicon dioxide present in an amount of about 0.55-0.95% by weight.
8. The tablet of claim 7 , 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.
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 60 mg of mannitol; and
about 4.5 mg of colloidal silicon dioxide.
10. The tablet of claim 2 , comprising about 3%-7% by weight crospovidone, and further comprising a glidant and a lubricant.
11. A 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, and
about 5-15% by weight mannitol.
12. The tablet of claim 11 , comprising about 65-75% by weight silicified microcrystalline cellulose, and about 7.5-12.5% by weight mannitol.
13. The tablet of claim 12 , comprising about 3-7% by weight crospovidone and further comprising a lubricant.
14. The tablet of claim 13 , wherein the lubricant is magnesium stearate present in an amount of about 0.55-0.95% by weight.
15. The tablet of claim 14 , 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.
16. The tablet of claim 13 , 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.
17. The tablet of claim 12 , further comprising a glidant, wherein the glidant is colloidal silicon dioxide present in an amount of about 0.55-0.95% by weight.
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;
crospovidone;
about 60 mg-100 mg of mannitol; and
about 4.4 mg-7.6 mg of colloidal silicon dioxide.
19. The tablet of claim 18 , 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.
20. The tablet of claim 12 , comprising about 3%-7% by weight crospovidone, and further comprising a glidant and a lubricant.
21. The tablet of claim 20 , wherein the glidant is colloidal silicon dioxide and the lubricant is magnesium stearate.
22. The tablet of claim 21 , 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.
23. The tablet of claim 21 , 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.
24. 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 40 mg of crospovidone;
about 80 mg of mannitol; and
colloidal silicon dioxide and magnesium stearate.
25. The tablet of claim 10 , wherein the glidant is colloidal silicon dioxide and the lubricant is magnesium stearate.
26. The tablet of claim 25 , 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.
27. The tablet of claim 25 , 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.
28. 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 30 mg of crospovidone;
about 60 mg of mannitol; and
colloidal silicon dioxide and magnesium stearate.