US 12,329,767 B2
Stable ready to use cyclophosphamide liquid formulations
Kocherlakota Chandrashekhar, Secunderabad (IN); and Banda Nagaraju, Hyderabad (IN)
Assigned to INGENUS PHARMACEUTICALS, LLC, Orlando, FL (US)
Filed by INGENUS PHARMACEUTICALS, LLC, Orlando, FL (US)
Filed on Apr. 6, 2021, as Appl. No. 17/223,096.
Application 17/223,096 is a continuation of application No. 15/551,507, granted, now 10,993,952, previously published as PCT/IB2016/050788, filed on Feb. 15, 2016.
Claims priority of application No. 735/CHE/2015 (IN), filed on Feb. 16, 2015; and application No. 3117/CHE/2015 (IN), filed on Jun. 22, 2015.
Prior Publication US 2021/0220375 A1, Jul. 22, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/675 (2006.01); A61K 9/00 (2006.01); A61K 9/08 (2006.01); A61K 47/10 (2017.01)
CPC A61K 31/675 (2013.01) [A61K 9/0019 (2013.01); A61K 9/08 (2013.01); A61K 47/10 (2013.01)] 12 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.