Claims for Patent: 12,558,317

Summary for Patent: 12,558,317

Title:	Compositions and methods for treating disorders ameliorated by muscarinic receptor activation
Abstract:	Provided herein is an oral pharmaceutical composition, comprising a plurality of xanomeline beads having a core comprising xanomeline or a salt thereof; and a plurality of trospium beads having a core comprising a salt of trospium.
Inventor(s):	Aimesther BETANCOURT, Bruce Rehlaender, Roch Thibert
Assignee:	Karuna Therapeutics Inc
Application Number:	US18/392,891
Patent Claims:	1. A pharmaceutical composition comprising xanomeline or a pharmaceutically acceptable salt thereof; trospium chloride; and 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium. 2. The pharmaceutical composition of claim 1, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.25 wt. % of the pharmaceutical composition. 3. The pharmaceutical composition of claim 1, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition. 4. The pharmaceutical composition of claim 1, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2wt. % of the pharmaceutical composition. 5. The pharmaceutical composition of claim 1, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition. 6. The pharmaceutical composition of claim 2, wherein the xanomeline or a pharmaceutically acceptable salt thereof is formulated as a first component, and the trospium chloride is formulated as a second component. 7. The pharmaceutical composition of claim 6, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition. 8. The pharmaceutical composition of claim 6, wherein the 3- [(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2wt. % of the pharmaceutical composition. 9. The pharmaceutical composition of claim 6, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition. 10. The pharmaceutical composition of claim 6, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity. 11. The pharmaceutical composition of claim 10, wherein the xanomeline is xanomeline tartrate. 12. The pharmaceutical composition of claim 6, wherein the first component further comprises a first excipient, and the second component further comprises a second excipient. 13. The pharmaceutical composition of claim 12, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition. 14. The pharmaceutical composition of claim 12, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2wt. % of the pharmaceutical composition. 15. The pharmaceutical composition of claim 12, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition. 16. The pharmaceutical composition of claim 12, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3months at 40°° C. and 75% relative humidity. 17. The pharmaceutical composition of claim 16, wherein the xanomeline is xanomeline tartrate. 18. The pharmaceutical composition of claim 6, wherein the first component further comprises microcrystalline cellulose; and the second component further comprises microcrystalline cellulose, lactose, or a combination thereof. 19. The pharmaceutical composition of claim 18, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition. 20. The pharmaceutical composition of claim 18, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition. 21. The pharmaceutical composition of claim 18, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition. 22. The pharmaceutical composition of claim 18, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity. 23. The pharmaceutical composition of claim 22, wherein the xanomeline is xanomeline tartrate. 24. The pharmaceutical composition of claim 12, wherein the first component is a first plurality of beads, and the second component is a second plurality of beads. 25. The pharmaceutical composition of claim 24, wherein the 3-[(4-hexyloxy)-1,2,5 -thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition. 26. The pharmaceutical composition of claim 24, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition. 27. The pharmaceutical composition of claim 24, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition. 28. The pharmaceutical composition of claim 24, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity. 29. The pharmaceutical composition of claim 28, wherein the xanomeline is xanomeline tartrate. 30. The pharmaceutical composition of claim 29, wherein the first plurality of beads and the second plurality of beads have a dissolution rate of more than about 80% within the first 30 minutes following entry of the pharmaceutical composition into a 0.1 N HCI solution. 31. The pharmaceutical composition of claim 24, wherein the first excipient comprises microcrystalline cellulose; and the second excipient comprises microcrystalline cellulose, lactose, or a combination thereof. 32. The pharmaceutical composition of claim 31, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition. 33. The pharmaceutical composition of claim 31, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition. 34. The pharmaceutical composition of claim 31, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition. 35. The pharmaceutical composition of claim 31, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity. 36. The pharmaceutical composition of claim 35, wherein the xanomeline is xanomeline tartrate. 37. The pharmaceutical composition of claim 36, wherein the first plurality of beads and the second plurality of beads have a dissolution rate of more than about 80% within the first 30 minutes following entry of the pharmaceutical composition into a 0.1 N HCl solution. 38. The pharmaceutical composition of claim 1, further comprising an antioxidant. 39. The pharmaceutical composition of claim 38, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.25 wt. % of the pharmaceutical composition. 40. The pharmaceutical composition of claim 39, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition. 41. The pharmaceutical composition of claim 39, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition. 42. The pharmaceutical composition of claim 39, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition. 43. The pharmaceutical composition of claim 39, wherein the antioxidant and the xanomeline or a pharmaceutically acceptable salt thereof are formulated as a first component, and the trospium chloride is formulated as a second component. 44. The pharmaceutical composition of claim 43, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity. 45. The pharmaceutical composition of claim 44, wherein the antioxidant is ascorbic acid. 46. The pharmaceutical composition of claim 45, wherein the xanomeline is xanomeline tartrate. 47. The pharmaceutical composition of claim 43, wherein the first component further comprises a first excipient, and the second component further comprises a second excipient. 48. The pharmaceutical composition of claim 47, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition. 49. The pharmaceutical composition of claim 47, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition. 50. The pharmaceutical composition of claim 47, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition. 51. The pharmaceutical composition of claim 47, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity. 52. The pharmaceutical composition of claim 48, wherein the antioxidant is ascorbic acid. 53. The pharmaceutical composition of claim 52, wherein the xanomeline is xanomeline tartrate. 54. The pharmaceutical composition of claim 43, wherein the first component further comprises microcrystalline cellulose; and the second component further comprises microcrystalline cellulose, lactose, or a combination thereof. 55. The pharmaceutical composition of claim 54, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition. 56. The pharmaceutical composition of claim 54, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition. 57. The pharmaceutical composition of claim 54, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition. 58. The pharmaceutical composition of claim 54, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity. 59. The pharmaceutical composition of claim 58, wherein the antioxidant is ascorbic acid. 60. The pharmaceutical composition of claim 59, wherein the xanomeline is xanomeline tartrate. 61. The pharmaceutical composition of claim 47, wherein the first component is a first plurality of beads, and the second component is a second plurality of beads. 62. The pharmaceutical composition of claim 61, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition. 63. The pharmaceutical composition of claim 61, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition. 64. The pharmaceutical composition of claim 61, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition. 65. The pharmaceutical composition of claim 61, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity. 66. The pharmaceutical composition of claim 65, wherein the antioxidant is ascorbic acid. 67. The pharmaceutical composition of claim 66, wherein the xanomeline is xanomeline tartrate. 68. The pharmaceutical composition of claim 67, wherein the first plurality of beads and the second plurality of beads have a dissolution rate of more than about 80% within the first 30 minutes following entry of the pharmaceutical composition into a 0.1 N HCl solution. 69. The pharmaceutical composition of claim 61, wherein the first excipient comprises microcrystalline cellulose; and the second excipient comprises microcrystalline cellulose, lactose, or a combination thereof. 70. The pharmaceutical composition of claim 69, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition. 71. The pharmaceutical composition of claim 69, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition. 72. The pharmaceutical composition of claim 69, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition. 73. The pharmaceutical composition of claim 69, wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity. 74. The pharmaceutical composition of claim 73, wherein the antioxidant is ascorbic acid. 75. The pharmaceutical composition of claim 74, wherein the xanomeline is xanomeline tartrate. 76. The pharmaceutical composition of claim 75, wherein the first plurality of beads and the second plurality of beads have a dissolution rate of more than about 80% within the first 30 minutes following entry of the pharmaceutical composition into a 0.1 N HCl solution.