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 or 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 70-90% by weight of a combination of a first filler and a second filler;
about 3-7% by weight disintegrant;
about 0.55-0.95% by weight colloidal silicon dioxide; and
about 0.45-1% by weight lubricant;
wherein the first filler is mannitol; and wherein the tablet comprises at least 10% by weight mannitol.
2. The tablet of claim 1 , wherein the second filler is silicified microcrystalline cellulose.
3. The tablet of claim 1 , wherein the disintegrant is crospovidone.
4. The tablet of claim 1 , comprising about 5% by weight disintegrant.
5. The tablet of claim 4 , 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.
6. The tablet of claim 5 , comprising about 0.75% by weight colloidal silicon dioxide and about 0.75% by weight lubricant, wherein the lubricant is magnesium stearate.
7. The tablet of claim 5 , wherein the disintegrant is crospovidone.
8. The tablet of claim 7 , comprising about 0.75% by weight colloidal silicon dioxide and about 0.75% by weight lubricant.
9. The tablet of claim 8 , wherein the lubricant is magnesium stearate.
10. The tablet of claim 1 , 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 560 mg-720 mg of the combination of the first filler and the second filler;
about 24 mg-56 mg disintegrant;
about 4.4 mg-7.6 mg colloidal silicon dioxide; and
about 3.6 mg-8 mg lubricant;
wherein the first filler is mannitol; and wherein the tablet comprises at least 80 mg mannitol.
11. The tablet of claim 10 , comprising about 40 mg disintegrant.
12. The tablet of claim 11 , comprising about 6 mg colloidal silicon dioxide and about 6 mg lubricant, wherein the lubricant is magnesium stearate.
13. The tablet of claim 11 , wherein the disintegrant is crospovidone.
14. The tablet of claim 13 , comprising about 6 mg colloidal silicon dioxide and about 6 mg lubricant.
15. The tablet of claim 14 , wherein the lubricant is magnesium stearate.
16. 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.
17. The tablet of claim 16 , comprising about 0.75% by weight colloidal silicon dioxide and about 0.75% by weight lubricant.
18. The tablet of claim 17 , wherein the lubricant is magnesium stearate.
19. The tablet of claim 16 , wherein the disintegrant is crospovidone.
20. The tablet of claim 19 , comprising about 0.75% by weight colloidal silicon dioxide and about 0.75% by weight lubricant.
21. The tablet of claim 20 , wherein the lubricant is magnesium stearate.
22. The tablet of claim 1 , 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 420 mg-540 mg of the combination of the first filler and the second filler;
about 24 mg-42 mg disintegrant;
about 3.3 mg-5.7 mg colloidal silicon dioxide; and
about 2.7 mg-6 mg lubricant, wherein the lubricant is magnesium stearate;
wherein the first filler is mannitol; and wherein the tablet comprises at least 10% by weight mannitol.
23. The tablet of claim 22 , comprising about 40 mg disintegrant.
24. The tablet of claim 23 , comprising about 4.5 mg colloidal silicon dioxide and about 4.5 mg magnesium stearate.
25. The tablet of claim 22 , comprising about 30 mg disintegrant, wherein the disintegrant is crospovidone.
26. The tablet of claim 25 , comprising about 4.5 mg colloidal silicon dioxide and about 4.5 mg of magnesium stearate.
27. A pharmaceutical tablet comprising:
about 75 mg or 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 filler;
about 7.5-12.5% by weight mannitol;
about 3-7% by weight disintegrant;
colloidal silicon dioxide; and
about 0.45-1% by weight magnesium stearate.
28. The tablet of claim 27 , wherein the filler is silicified microcrystalline cellulose and the tablet comprises about 0.55-0.95% by weight colloidal silicon dioxide.
29. The tablet of claim 28 , wherein the disintegrant is crospovidone.
30. The tablet of claim 27 , wherein the filler is silica fine microcrystalline cellulose and the disintegrant is crospovidone.