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 filler;
about 2-8% by weight disintegrant; and
about 10% by weight mannitol.
2. The tablet of claim 1 , comprising about 65-75% by weight filler.
3. The tablet of claim 2 , further comprising a glidant.
4. The tablet of claim 3 , wherein the glidant is colloidal silica.
5. The tablet of claim 4 , wherein the colloidal silica is present in an amount of about 0.55-0.95% by weight.
6. The tablet of claim 2 , further comprising a lubricant, wherein the lubricant is magnesium stearate.
7. The tablet of claim 6 , wherein the magnesium stearate is present in an amount of about 0.45-1.0% by weight.
8. The tablet of claim 3 , further comprising a lubricant, wherein the lubricant is magnesium stearate.
9. The tablet of claim 8 , wherein the magnesium stearate is present in an amount of about 0.45-1.0% by weight.
10. The tablet of claim 1 , wherein the disintegrant is crospovidone.
11. 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 390 mg 450 mg filler;
about 12 mg 48 mg disintegrant;
about 60 mg of mannitol;
colloidal silica; and
magnesium stearate.
12. The tablet of claim 11 , wherein the filler is silicified microcrystalline cellulose, and the disintegrant is crospovidone.
13. 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 filler;
about 2-8% by weight disintegrant; and
about 10% by weight mannitol.
14. The tablet of claim 13 , comprising about 65-75% by weight filler.
15. The tablet of claim 14 , further comprising a glidant.
16. The tablet of claim 15 , wherein the glidant is colloidal silica.
17. The tablet of claim 16 , wherein the colloidal silica is present in an amount of about 0.55-0.95% by weight.
18. The tablet of claim 14 , further comprising a lubricant, wherein the lubricant is magnesium stearate.
19. The tablet of claim 18 , wherein the magnesium stearate is present in an amount of about 0.45-1.0% by weight.
20. The tablet of claim 15 , further comprising a lubricant, wherein the lubricant is magnesium stearate.
21. The tablet of claim 20 , wherein the magnesium stearate is present in an amount of about 0.45-1.0% by weight.
22. The tablet of claim 13 , wherein the disintegrant is crospovidone.
23. 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 520 mg-600 mg of filler;
about 16 mg-64 mg of disintegrant;
about 80 mg of mannitol;
colloidal silica; and
magnesium stearate.
24. The tablet of claim 23 , wherein the filler is silicified microcrystalline cellulose, and the disintegrant is crospovidone.
25. The pharmaceutical tablet of claim 11 , 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 filler;
about 42 mg disintegrant;
about 60 mg mannitol;
about 12 mg colloidal silica;
about 6 mg magnesium stearate; and
about 18 mg of a film coating,
wherein the nominal weight of the tablet without the film coating is about 600 mg and the total weight of the tablet is about 618 mg.
26. The pharmaceutical 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 390 mg-450 mg silicified microcrystalline cellulose;
about 30 mg crospovidone;
about 60 mg mannitol;
about 4.5 mg magnesium stearate; and
about 18 mg of a film coating,
wherein the nominal weight of the tablet without the film coating is about 600 mg and the total weight of the tablet is about 618 mg.
27. The pharmaceutical tablet of claim 26 , consisting of:
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 426 mg silicified microcrystalline cellulose;
about 30 mg crospovidone;
about 60 mg mannitol;
about 4.5 mg magnesium stearate; and
about 18 mg of a film coating,
wherein the nominal weight of the tablet without the film coating is about 600 mg and the total weight of the tablet is about 618 mg.
28. The pharmaceutical 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 filler;
about 56 mg of disintegrant;
about 80 mg of mannitol;
about 16 mg of colloidal silica;
about 8 mg of magnesium stearate; and
about 24 mg of a film coating,
wherein the nominal weight of the tablet without the film coating is about 800 mg and the total weight of the tablet is about 824 mg.
29. The pharmaceutical 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;
about 6 mg of magnesium stearate; and
about 24 mg of a film coating,
wherein the nominal weight of the tablet without the film coating is about 800 mg and the total weight of the tablet is about 824 mg.
30. The pharmaceutical tablet of claim 29 , consisting of:
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 568 mg of silicified microcrystalline cellulose;
about 40 mg of crospovidone;
about 80 mg of mannitol;
about 6 mg of magnesium stearate; and
about 24 mg of a film coating,
wherein the nominal weight of the tablet without the film coating is about 800 mg and the total weight of the tablet is about 824 mg.