Claims for Patent: 12,329,767

Summary for Patent: 12,329,767

Title:	Stable ready to use cyclophosphamide liquid formulations
Abstract:	The present invention relates to stable ready to use liquid formulations of Cyclophosphamide for parenteral use. The ready to use composition comprises Cyclophosphamide dissolved in a solvent system comprising a solvent, cosolvent(s) and antioxidant(s).
Inventor(s):	Kocherlakota CHANDRASHEKHAR, Banda NAGARAJU
Assignee:	Ingenus Pharmaceuticals LLC
Application Number:	US17/223,096
Patent Claims:	1. A stable liquid parenteral formulation of cyclophosphamide comprising: i) cyclophosphamide in a concentration of 10.72% to 22.62% based on total formulation weight; ii) an ethanol content of 70.26% to 75.88% based on total formulation weight; iii) both polyethylene glycol and propylene glycol, wherein a polyethylene glycol to propylene glycol mass ratio is between approximately 1.0:1.0 to approximately 2.0:1.0, the polyethylene glycol content being from 3.38% to 8.90% and the propylene glycol content being from 3.38% to 4.50%, based on total formulation weight; iv) less than 3% based on total formulation weight of an antioxidant selected from the group consisting of sulphur-containing antioxidants, butylated hydroxyl anisole, butylated hydroxyl toluene, citric acid, lactic acid, benzoic acid, tocopherol, monothioglycerol, ascorbic acid, L-cysteine, methyl paraben, benzyl alcohol, propyl gallate, thioglycolic acid, tartaric acid, thiodipropionic acid, complexing agents, and amino acids; and v) optionally other pharmaceutically acceptable adjuvants, wherein, after storage for 7 days at 40° C./75% RH, decomposition to form any of the following impurities occurs less than 0.5%: a) bis(2-chloroethyl)amine hydrochloride; b) 3-(2-chloroethyl)-2-oxo-2-hydroxy-1,3,6,2-oxadiazaphosphonane; and c) 3-[2-(2-chloroethylamino)ethyl amino]propyl dihydrogen phosphate dihydrochloride. 2. The stable liquid parenteral formulation of claim 1 further comprising up to 20% water for injection. 3. The stable liquid parenteral formulation of claim 1, wherein the antioxidant is selected from the group consisting of monothioglycerol, butylated hydroxyanisole, butylated hydroxyl toluene, citric acid, L-cysteine, and ascorbic acid. 4. The stable liquid parenteral formulation of claim 3, wherein the antioxidant is monothioglycerol in a concentration of 0.01% to 0.02% based on total formulation weight. 5. The stable liquid parenteral formulation of claim 4, wherein the cyclophosphamide concentration is about 10.72%, the ethanol content is about 75.88%, the polyethylene glycol content is about 8.90%, and the propylene glycol content is about 4.50%, all based on total formulation weight. 6. The stable liquid parenteral formulation of claim 5, wherein the monothioglycerol concentration is about 0.01% based on total formulation weight. 7. The stable liquid parenteral formulation of claim 4, wherein the cyclophosphamide concentration is about 12.00%, the ethanol content is about 74.78%, the polyethylene glycol content is about 8.80%, and the propylene glycol content is about 4.41%, all based on total formulation weight. 8. The stable liquid parenteral formulation of claim 7, wherein the monothioglycerol concentration is about 0.01% based on total formulation weight. 9. The stable liquid parenteral formulation of claim 4, wherein the cyclophosphamide concentration is about 22.62%, the ethanol content is about 70.58%, the polyethylene glycol content is about 3.39%, and the propylene glycol content is about 3.39%, all based on total formulation weight. 10. The stable liquid parenteral formulation of claim 9, wherein the monothioglycerol concentration is about 0.02% based on total formulation weight. 11. The stable liquid parenteral formulation of claim 4, wherein the cyclophosphamide concentration is about 22.52%, the ethanol content is about 70.26%, the polyethylene glycol content is about 3.38%, and the propylene glycol content is about 3.38%, all based on total formulation weight. 12. The stable liquid parenteral formulation of claim 11, wherein the monothioglycerol concentration is about 0.02% based on total formulation weight.