Claims for Patent: 11,389,448

Summary for Patent: 11,389,448

Title:	Freeze dried drug nanosuspensions
Abstract:	The present invention relates to a freeze-dried (also called lyophilized) drug nanosuspension. The present freeze-dried drug nanosuspension composition has an acceptable stability of the particle size distribution during storage, including long term storage.
Inventor(s):	Sabine Karine Katrien INGHELBRECHT, Jakob Andreas Beirowski, Henning Gieseler
Assignee:	Janssen Pharmaceutica NV
Application Number:	US16/184,791
Patent Claims:	1. A nanosuspension comprising about 200-400 mg/ml of nanoparticles of a drug that is 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile or a stereoisomeric form thereof; or a pharmaceutically acceptable salt thereof, wherein the nanoparticles have an average particle size of below about 1000 nm, about 50 to 75 mg/ml of a poloxamer, about 10 to 50 mg/ml of a cryoprotectant comprising a monosaccharide, a disaccharide, or mannitol; and water; wherein lyophilization of the nanosuspension produces a freeze dried composition having a re-dispersibility index of at least 90% after reconstitution of the freeze-dried composition with water after 3 months storage at 25° C. 2. The nanosuspension of claim 1, comprising about 200 mg/ml of the drug. 3. The nanosuspension of claim 1, comprising about 300 mg/ml of the drug. 4. The nanosuspension of claim 1, wherein the drug is 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile base. 5. The nanosuspension of claim 1, wherein the drug is E-4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile. 6. The nanosuspension of claim 1, wherein the cryoprotectant comprises sucrose. 7. The nanosuspension of claim 1, wherein the cryoprotectant comprises trehalose. 8. The nanosuspension of claim 1, wherein the cryoprotectant comprises mannitol. 9. The nanosuspension of claim 1, comprising about 50 mg/ml of the cryoprotectant. 10. The nanosuspension of claim 1, comprising about 50 mg/ml of the poloxamer. 11. The nanosuspension of claim 1, wherein the nanoparticles have an average particle size of about 200 nm. 12. The nanosuspension of claim 1, wherein the nanoparticles have an average particle size of about 400 nm. 13. The nanosuspension of claim 1, wherein the nanoparticles have an average particle size of about 800 nm. 14. The nanosuspension of claim 1, comprising 10 mg/ml of the cryoprotectant. 15. The nanosuspension of claim 1, comprising 12.5 mg/ml of the cryoprotectant. 16. The nanosuspension of claim 1, comprising 20 mg/ml of the cryoprotectant. 17. The nanosuspension of claim 1, comprising 25 mg/ml of the cryoprotectant. 18. The nanosuspension of claim 1, comprising 75 mg/ml of the poloxamer. 19. A freeze-dried composition with a re-dispersibility index of at least 90% after 3 months storage at 25° C., wherein reconstitution of the freeze-dried composition with water produces a nanosuspension which comprises about 200-400 mg/ml of nanoparticles of a drug that is 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile or a stereoisomeric form thereof; or a pharmaceutically acceptable salt thereof, wherein the nanoparticles have an average particle size of below about 1000 nm, about 50 to 75 mg/ml of a poloxamer, and about 10 to 50 mg/ml of a cryoprotectant comprising a monosaccharide, a disaccharide, or mannitol. 20. A freeze-dried composition derived from a nanosuspension comprising about 200-400 mg/ml of nanoparticles of a drug that is 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile or a stereoisomeric form thereof; or a pharmaceutically acceptable salt thereof, wherein the nanoparticles have an average particle size of below about 1000 nm, about 50 to 75 mg/ml of a poloxamer, about 10 to 50 mg/ml of a cryoprotectant comprising a monosaccharide, a disaccharide, or mannitol; and water; wherein the freeze-dried composition has a re-dispersibility index of at least 90% after 3 months storage at 25° C. 21. The freeze-dried composition of claim 20, wherein the nanosuspension comprises about 200 mg/ml of the drug. 22. The freeze-dried composition of claim 20, wherein the nanosuspension comprises about 300 mg/ml of the drug. 23. The freeze-dried composition of claim 20, wherein the nanosuspension comprises about 400 mg/ml of the drug. 24. The freeze-dried composition of claim 20, wherein the nanoparticles have an average particle size of about 400 nm. 25. The freeze-dried composition of claim 20, wherein the nanoparticles have an average particle size of about 800 nm. 26. The freeze-dried composition of claim 20, wherein the nanoparticles have an average particle size of about 200 nm. 27. The freeze-dried composition of claim 20, wherein the nanosuspension comprises about 50 mg/ml of the poloxamer. 28. The freeze-dried composition of claim 20, wherein the nanosuspension comprises about 75 mg/ml of the poloxamer. 29. The freeze-dried composition of claim 20, wherein the nanosuspension comprises about 10 mg/ml of the cryoprotectant. 30. The freeze-dried composition of claim 20, wherein the nanosuspension comprises about 12.5 mg/ml of the cryoprotectant. 31. The freeze-dried composition of claim 20, wherein the nanosuspension comprises about 20 mg/ml of the cryoprotectant. 32. The freeze-dried composition of claim 20, wherein the nanosuspension comprises about 25 mg/ml of the cryoprotectant. 33. The freeze-dried composition of claim 20, wherein the nanosuspension comprises about 50 mg/ml of the cryoprotectant.