Claims for Patent: 10,849,916

Summary for Patent: 10,849,916

Title:	Stable liquid formulations of cyclophosphamide and its impurities
Abstract:	The present invention relates to novel impurities of cyclophosphamide having structure V, VI or VII, stabilized form of these novel impurities, a process of preparing a stabilized form and isolating thereof. The invention also relates cyclophosphamide formulations which include cyclophosphamide, at least one pharmaceutically acceptable excipient, and a certain level of these impurities having structure V, VI or VII. The invention further relate to method of using such stable liquid formulations of cyclophosphamide for parenteral administration in treating various cancer disorders.
Inventor(s):	Riyaz Ahmed Shaik, Ananya SAHA, SVB Janardhan Garikipati, Akash CHAURASIYA, Bhavesh Vallabhbhai PATEL, Harshal BHAGWATWAR, Sumitra Ashok Pillai, Satheesh Balasubramanian, Joydeep MAZUMDER
Assignee:	Avyxa Holdings LLC
Application Number:	US16/414,418
Patent Claims:	1. A compound of the structure V 2. A compound of the structure VI 3. A compound of the structure VII 4. A stabilized form of the compound of structure V wherein stabilized form of compound of structure V comprises at least one stabilizer selected from the group comprising of mannitol, sorbitol, xylitol, maltitol, tartaric acid, citric acid, malic acid, oxalic acid; sodium carbonate, sodium bicarbonate, sodium chloride, lactose, sucrose, maltose, starch. 5. A stabilized form of the compound of structure VI wherein stabilized form of compound of structure VI comprises at least one stabilizer selected from the group comprising of mannitol, sorbitol, xylitol, maltitol, tartaric acid, citric acid, malic acid, oxalic acid; sodium carbonate, sodium bicarbonate, sodium chloride, lactose, sucrose, maltose, starch. 6. A stabilized form of the compound of structure VII wherein stabilized form of compound of structure VII comprises at least one stabilizer selected from the group comprising of mannitol, sorbitol, xylitol, maltitol, tartaric acid, citric acid, malic acid, oxalic acid; sodium carbonate, sodium bicarbonate, sodium chloride, lactose, sucrose, maltose, starch. 7. A stabilized form of the compound according to claim 4, wherein stabilizer is mannitol. 8. A stabilized form of the compound according to claim 5, wherein stabilizer is mannitol. 9. A stabilized form of the compound according to claim 6, wherein stabilizer is mannitol. 10. A stabilized form of the compound according to the claim 4, having a ratio of the compound to stabilizer ranging from about 1:0.1 to about 1:25. 11. A stabilized form of the compound according to the claim 5, having a ratio of the compound to stabilizer ranging from about 1:0.1 to about 1:25. 12. A stabilized form of the compound according to the claim 6, having a ratio of the compound to stabilizer ranging from about 1:0.1 to about 1:25. 13. A cyclophosphamide formulation comprising cyclophosphamide, a compound of structure V, and at least one pharmaceutically acceptable excipient, wherein the level of the compound of structure V in the formulation is less than about 2.5% by weight. 14. A cyclophosphamide formulation comprising cyclophosphamide, a compound of structure VI, and at least one pharmaceutically acceptable excipient, wherein the level of compound of structure VI in the formulation is less than about 2.5% by weight 15. A cyclophosphamide formulation comprising cyclophosphamide, a compound of structure VII, and at least one pharmaceutically acceptable excipient, wherein the level of the compound of structure VII in the formulation is less than about 2.5% by weight. 16. The stable liquid formulation according to claim 13 wherein the cyclophosphamide in the formulation is cyclophosphamide monohydrate. 17. The stable liquid formulation according to claim 14 wherein the cyclophosphamide in the formulation is cyclophosphamide monohydrate. 18. The stable liquid formulation according to claim 15 wherein the cyclophosphamide in the formulation is cyclophosphamide monohydrate. 19. The stable liquid formulation according to claim 13 wherein the pharmaceutically acceptable excipient is selected from the group comprising of ethanol, polysorbate, cyclodextrin, dimethyl acetamide, polyethoxylated castor oil or combinations thereof. 20. The stable liquid formulation according to claim 14 wherein the pharmaceutically acceptable excipient is selected from the group comprising of ethanol, polysorbate, cyclodextrin, dimethyl acetamide, polyethoxylated castor oil or combinations thereof. 21. The stable liquid formulation according to claim 15 wherein the pharmaceutically acceptable excipient is selected from the group comprising of ethanol, polysorbate, cyclodextrin, dimethyl acetamide, polyethoxylated castor oil or combinations thereof. 22. The stable liquid formulation according to claim 19 wherein pharmaceutically acceptable excipient is ethanol. 23. The stable liquid formulation according to claim 20 wherein pharmaceutically acceptable excipient is ethanol. 24. The stable liquid formulation according to claim 21 wherein pharmaceutically acceptable excipient is ethanol.