Claims for Patent: 10,376,505
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Summary for Patent: 10,376,505
| Title: | Oral formulations and lipophilic salts of methylnaltrexone |
| Abstract: | The present invention provides compositions comprising methylnaltrexone or a salt thereof, and compositions and formulations thereof, for oral administration. |
| Inventor(s): | Shah; Syed M. (Delray Beach, FL), Diorio; Christopher Richard (Campbell Hall, NY), Ehrnsperger; Eric C. (New City, NY), Meng; Xu (San Diego, CA), Al Shareffi; Kadum A. (Greensboro, NC), Cohen; Jonathan Marc (Monroe, NY) |
| Assignee: | Wyeth, LLC (Madison, NJ) |
| Application Number: | 16/219,159 |
| Patent Claims: |
1. A pharmaceutical composition for oral administration comprising a solid dosage of (i) methylnaltrexone bromide, and (ii) sodium dodecyl sulfate (SDS), wherein the
composition is a tablet, wherein methylnaltrexone bromide is the sole active agent, and wherein the composition comprises from about 7% to about 75% methylnaltrexone cation and dodecyl sulfate anion, based upon the total weight of the composition.
2. The pharmaceutical composition of claim 1, wherein the tablet is not enterically coated. 3. The pharmaceutical composition of claim 2, further comprising a rapid-acting disintegrant. 4. The pharmaceutical composition of claim 3, wherein the rapid-acting disintegrant is an effervescent disintegrant. 5. The pharmaceutical composition of claim 3, wherein the rapid-acting disintegrant is sodium bicarbonate. 6. The pharmaceutical composition of claim 2, wherein at least 50% of the composition dissolves in a dissolution apparatus with paddles at 100 rpm in 900 mL of 0.1 N HCl at 37.degree. C. within about 15 minutes. 7. The pharmaceutical composition of claim 6, wherein at least 75% of the composition dissolves in a dissolution apparatus with paddles at 100 rpm in 900 mL of 0.1 N HCl at 37.degree. C. within about 15 minutes. 8. The pharmaceutical composition of claim 2, wherein at least 90% of the composition dissolves in a dissolution apparatus with paddles at 100 rpm in 900 mL of 0.1 N HCl at 37.degree. C. within about 15 minutes. 9. The pharmaceutical composition of claim 2, wherein an ion pair forms when the methylnaltrexone bromide and sodium dodecyl sulfate (SDS) are dissolved in solution. 10. The pharmaceutical composition of claim 9, wherein the solution is at a pH of about 1 to about 4. 11. The pharmaceutical composition of claim 3, wherein an ion pair forms when the methylnaltrexone bromide and sodium dodecyl sulfate (SDS) are dissolved in solution. 12. The pharmaceutical composition of claim 11, wherein the solution is at a pH of about 1 to about 4. 13. The pharmaceutical composition of claim 2, wherein the composition in solution has an apparent octanol/water partition coefficient for methylnaltrexone of at least 0.25 at a pH between 1 and 4. 14. The pharmaceutical composition of claim 13, wherein the apparent octanol/water partition coefficient for methylnaltrexone is at least 0.5. 15. The pharmaceutical composition of claim 13, wherein the apparent octanol/water partition coefficient for methylnaltrexone is at least 1. 16. The pharmaceutical composition of claim 1, wherein the ratio of methylnaltrexone bromide to sodium dodecyl sulfate in the tablet is about 3:1 by weight. 17. The pharmaceutical composition of claim 16, wherein the tablet is not enterically coated. 18. The pharmaceutical composition of claim 17, wherein at least 50% of the composition dissolves in a dissolution apparatus with paddles at 100 rpm in 900 mL of 0.1 N HCl at 37.degree. C. within about 15 minutes. 19. The pharmaceutical composition of claim 18, wherein at least 75% of the composition dissolves in a dissolution apparatus with paddles at 100 rpm in 900 mL of 0.1 N HCl at 37.degree. C. within about 15 minutes. 20. The pharmaceutical composition of claim 19, wherein at least 90% of the composition dissolves in a dissolution apparatus with paddles at 100 rpm in 900 mL of 0.1 N HCl at 37.degree. C. within about 15 minutes. 21. The pharmaceutical composition of claim 16, wherein an ion pair forms when the methylnaltrexone bromide and sodium dodecyl sulfate (SDS) are dissolved in solution. 22. The pharmaceutical composition of claim 21, wherein the solution is at a pH of about 1 to about 4. 23. The pharmaceutical composition of claim 1 made with methylnaltrexone bromide and sodium dodecyl sulfate in a ratio of about 3:1 by weight. 24. The pharmaceutical composition of claim 23, wherein the tablet is not enterically coated. 25. The pharmaceutical composition of claim 2, further comprising a chelating agent. 26. The pharmaceutical composition of claim 25, wherein the chelating agent is calcium EDTA disodium. 27. The pharmaceutical composition of claim 16, further comprising a chelating agent. 28. The pharmaceutical composition of claim 27, wherein the chelating agent is calcium EDTA disodium. 29. The pharmaceutical composition of claim 28, further comprising at least one of (i) a binder comprising microcrystalline cellulose and (ii) a glidant comprising colloidal silicon dioxide. 30. A pharmaceutical composition for oral administration comprising a solid dosage of (i) methylnaltrexone bromide, and (ii) sodium dodecyl sulfate (SDS), wherein the composition is a tablet, wherein methylnaltrexone bromide is the sole active agent, wherein the composition comprises about 7% to about 75% of methylnaltrexone cation and dodecyl sulfate anion, based upon total weight of the composition; and wherein the composition further comprises (a) a chelating agent comprising calcium EDTA disodium; (b) a binder comprising microcrystalline cellulose; (c) a glidant comprising colloidal silicon dioxide; and (d) magnesium stearate and talc. |
