Claims for Patent: 10,925,832

Summary for Patent: 10,925,832

Title:	Compositions and methods for treatment of 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:	US16/880,600
Patent Claims:	1. An oral pharmaceutical composition, comprising: a plurality of xanomeline beads having a size between 0.425 mm and 1.18 mm, and a core comprising between 30 wt. % and 80 wt. % xanomeline tartrate, between 15 wt. % and 65 wt. % microcrystalline cellulose, and between 0 wt. % and 2 wt. % talc; and a plurality of trospium beads having a size between 0.425 mm and 1.18 mm, and a core comprising between 8 wt. % and 35 wt. % trospium chloride, between 25 wt. % and 80 wt. % microcrystalline cellulose, between 15 wt. % and 70 wt. % lactose monohydrate, and between 0 wt. % and 2 wt. % talc; the plurality of xanomeline beads and the plurality of trospium beads each having a dissolution rate of more than about 95% within about the first 45 minutes following entry of the dosage form into an aqueous solution; and wherein, when administered to a patient for at least 7 days at 20 mg trospium twice daily, providing a mean Cmax of trospium at 7850±3360 pg/mL and a mean AUC0-12 of 41900±15500 hr·pg/mL. 2. The oral pharmaceutical composition of claim 1, wherein the size of the xanomeline beads is between 0.6 mm and 0.85 mm. 3. The oral pharmaceutical composition of claim 1, wherein the size of the trospium beads is between 0.6 mm and 0.85 mm. 4. The oral pharmaceutical composition of claim 1, wherein the xanomeline beads contain about 2.5 times as much xanomeline tartrate as the trospium beads contain trospium chloride. 5. The oral pharmaceutical composition claim 1, having a dissolution rate of the xanomeline tartrate and the trospium chloride of more than about 95% within about the first 20 minutes following entry of the dosage form into an aqueous solution. 6. The oral pharmaceutical composition claim 1, wherein the xanomeline beads comprise 66 wt. % xanomeline tartrate, 33.5 wt. % microcrystalline cellulose, and 0.5 wt. % talc. 7. The oral pharmaceutical composition claim 1, wherein the trospium beads comprise 17.7 wt. % trospium chloride, 46.8 wt. % microcrystalline cellulose, 35 wt. % lactose monohydrate, and 0.5 wt. % talc. 8. The oral pharmaceutical composition of claim 1, further comprising a capsule containing the plurality of xanomeline beads and the plurality of trospium beads. 9. An oral pharmaceutical composition, comprising: a capsule containing a plurality of xanomeline beads and a plurality of trospium beads; the plurality of xanomeline beads having a size between 0.6 mm and 0.85 mm, and a core comprising 66 wt. % xanomeline tartrate, 33.5 wt. % microcrystalline cellulose, and 0.5 wt. % talc; and the plurality of trospium beads having a size between 0.6 mm and 0.85 mm, and a core comprising 17.7 wt. % trospium chloride, 46.8 wt. % microcrystalline cellulose, 35 wt. % lactose monohydrate, and 0.5 wt. % talc; the plurality of xanomeline beads and the plurality of trospium beads each having a dissolution rate of more than about 95% within about the first 20 minutes following entry of the dosage form into an aqueous solution; and wherein, when administered to a patient for at least 7 days at 20 mg trospium twice daily, providing a mean Cmax of trospium at 7850±3360 pg/mL and a mean AUC0-12 of 41900±15500 hr·pg/mL. 10. The oral pharmaceutical composition of claim 9, wherein the capsule has a dosage strength of 25 mg xanomeline free base and 10 mg trospium chloride. 11. The oral pharmaceutical composition of claim 9, wherein the capsule has a dosage strength of 50 mg xanomeline free base and 20 mg trospium chloride. 12. The oral pharmaceutical composition of claim 9, wherein the capsule has a dosage strength of 50 mg xanomeline free base and 10 mg trospium chloride. 13. The oral pharmaceutical composition of claim 9, wherein the capsule has a dosage strength of 75 mg xanomeline free base and 10 mg trospium chloride. 14. The oral pharmaceutical composition of claim 9, wherein the capsule has a dosage strength of 75 mg xanomeline free base and 20 mg trospium chloride. 15. The oral pharmaceutical composition of claim 9, wherein the capsule has a dosage strength of 125 mg xanomeline free base and 20 mg trospium chloride. 16. The oral pharmaceutical composition of claim 9, wherein the capsule has a dosage strength of 125 mg xanomeline free base and 30 mg trospium chloride. 17. The oral pharmaceutical composition of claim 9, wherein the capsule has a dosage strength of 125 mg xanomeline free base and 40 mg trospium chloride. 18. The oral pharmaceutical composition of claim 9, wherein the xanomeline beads comprise less than 0.5 wt. % 3-[(4-hexyloxy)-1,2,5-thiadizaol-3-yl]-5-hydroyl-1-methylpyridin-1-ium.