Claims for Patent: 10,774,091

Summary for Patent: 10,774,091

Title:	Soft gelatin capsule formulation
Abstract:	The present invention generally relates to novel pharmaceutical formulations containing 2-[3,5-Bis(trifluoromethyl)phenyl]-N-{4-(4-fluoro-2-methylphenyl)-6-[(7S,9aS)-7-(hydroxymethyl)hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-3-pyridinyl}-N,2-dimethylpropanamide, methods of preparation thereof and their use in medical therapy.
Inventor(s):	Mike Trower, Monica Lazaro, Derek BUSH, David Elder, Mary Kerr
Assignee:	Kandy Therapeutics Ltd
Application Number:	US16/351,659
Patent Claims:	1. A soft gelatin capsule formulation, comprising: (a) 2-[3,5-Bis(trifluoromethyl)phenyl]-N-{4-(4-fluoro-2-methylphenyl)-6-[(7S,9aS)-7-(hydroxymethyl)hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-3-pyridinyl}-N,2-dimethylpropanamide (Compound A): or a pharmaceutically acceptable salt thereof; (b) at least one solubilizer selected from caprylocaproyl polyoxyl-8 glycerides, glycerol monocaprylocaprate, polyoxyl 35 castor oil, polysorbate 80, or mixtures thereof; and (c) at least one antioxidant selected from dl-alpha-tocopherol, butylated hydroxytoluene, butylated hydroxyanisole, or mixtures thereof. 2. The formulation of claim 1, wherein Compound A is in a crystalline form. 3. The formulation of claim 1, wherein Compound A is a crystalline form characterized by an XRPD pattern having a 2 theta angle peak at 4.3±0.1 degree, 7.9±0.1 degree, 9.8±0.1 degree, 10.7±0.1 degree, 10.8±0.1 degree, 13.3±0.1 degree, 14.0±0.1 degree, and 15.1±0.1 degree, which correspond respectively to d-spacing at 20.4, 11.1, 9.0, 8.3, 8.2, 6.6, 6.3 and 5.9 Angstroms (A). 4. The formulation of claim 1, further comprising (d) at least one emulsifier selected from glyceryl monooleate, Miglyol 812, or a mixture thereof. 5. The formulation of claim 1, further comprising one or more additional therapeutic agents. 6. The formulation of claim 1, wherein Compound A is present in the formulation at a concentration from 0.8% w/w to 15% w/w. 7. The formulation of claim 1, wherein Compound A is present in the formulation in an amount from 10 mg to 80 mg. 8. The formulation of claim 1, wherein at least one solubilizer is selected from glycerol monocaprylocaprate, caprylocaproyl polyoxyl-8 glycerides, or polysorbate 80. 9. The formulation of claim 4, wherein at least one emulsifier is glyceryl monooleate. 10. The formulation of claim 1, wherein at least one antioxidant is dl-alpha-tocopherol. 11. The formulation of claim 1, comprising (a) Compound A; (b1) glycerol monocaprylocaprate; (b2) caprylocaproyl polyoxyl-8-glycerides; (b3) polysorbate 80; and (c) dl-alpha-tocopherol. 12. The formulation of claim 1, comprising (a) Compound A; (b1) glycerol monocaprylocaprate; (b2) caprylocaproyl polyoxyl-8-glycerides; (b3) polysorbate 80; (c) dl-alpha-tocopherol; and (d) glyceryl monooleate. 13. The formulation of claim 1, wherein Compound A is present in the formulation at a concentration ranging from 5% w/w to 10% w/w. 14. The formulation of claim 8, wherein glycerol monocaprylocaprate is present in the formulation at a concentration ranging from 20% w/w to 65% w/w. 15. The formulation of claim 8, wherein caprylocaproyl polyoxyl-8 glycerides is present in the formulation at a concentration ranging from 7% w/w to 13% w/w. 16. The formulation of claim 8, wherein polysorbate 80 is present in the formulation at a concentration from 7% w/w to 13% w/w. 17. The formulation of claim 9, wherein glyceryl monooleate is present in the formulation at a concentration ranging from 15% w/w to 60% w/w. 18. The formulation of claim 10, wherein dl-alpha-tocopherol is present in the formulation at a concentration ranging from 0.05% w/w to 1.5% w/w. 19. A soft gelatin capsule formulation comprising: (a) Compound A present at a concentration ranging from 5% w/w to 10% w/w; (b1) glycerol monocaprylocaprate present at a concentration ranging from 20% w/w to 65% w/w; (b2) caprylocaproyl polyoxyl-8 glycerides present at a concentration ranging from 7% w/w to 13% w/w; (b3) polysorbate 80 present at a concentration from 7% w/w to 13% w/w; (c) dl-alpha-tocopherol present at a concentration ranging from 0.5% w/w to 1% w/w; and (d) glyceryl monooleate. 20. The formulation of claim 19, wherein glyceryl monooleate is present in the formulation at a concentration ranging from 15% w/w to 60% w/w. 21. The formulation of claim 19, being prepared by a method comprising adding Compound A to a mixture comprising 15% w/w to 60% w/w glyceryl monooleate, glycerol monocaprylocaprate, caprylocaproyl polyoxyl-8 glycerides, polysorbate 80, or dl-alpha-tocopherol. 22. A soft gelatin capsule formulation comprising: (a) Compound A present at a concentration ranging from 1% w/w to 10% w/w; (b1) glycerol monocaprylocaprate present at a concentration ranging from 30% w/w to 40% w/w; (b2) caprylocaproyl polyoxyl-8 glycerides present at a concentration ranging from 7% w/w to 13% w/w; (b3) polysorbate 80 present at a concentration from 7% w/w to 13% w/w; (c) dl-alpha-tocopherol present at a concentration ranging from 0.5% w/w to 1% w/w; and (d) glyceryl monooleate. 23. The formulation of claim 22, wherein glyceryl monooleate is present in the formulation at a concentration ranging from 33% w/w to 43% w/w. 24. The formulation of claim 22, being prepared by a method comprising adding Compound A to a mixture comprising 33% w/w to 43% w/w glyceryl monooleate, glycerol monocaprylocaprate, caprylocaproyl polyoxyl-8 glycerides, polysorbate 80, and dl-alpha-tocopherol.