Pharmaceutical compositions and methods of making pharmaceutical compositions comprising 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate
Provided are novel formulations of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate as described below and uses thereof.
1. A pharmaceutical composition comprising 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate (Formula I)
and one or more Bronsted bases, wherein the one or more Bronsted bases are an amine and/or a salt thereof, and the pharmaceutical composition comprises <2% N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide after one week at room temperature.
2. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is suitable for dissolution with an aqueous solution to form an injection.
3. The pharmaceutical composition of claim 2 , wherein upon dissolution of the pharmaceutical composition in the aqueous solution the pharmaceutical composition has a pH between 7 and 9.5.
4. The pharmaceutical composition of claim 2 , wherein upon dissolution of the pharmaceutical composition in the aqueous solution the pharmaceutical composition has a pH between 8 and 9.5.
5. The pharmaceutical composition of claim 2 , wherein upon dissolution of the pharmaceutical composition in the aqueous solution the pharmaceutical composition has a pH between 8 and 8.5.
6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises <1% N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide after one week at room temperature.
7. The pharmaceutical composition of claim 1 , wherein a conjugate acid of the one or more Bronsted bases has a pKa between 6 and 11.
8. The pharmaceutical composition of claim 1 , wherein a conjugate acid of the one or more Bronsted bases has a pKa between 8 and 10.
9. The pharmaceutical composition of claim 1 , wherein the one or more Bronsted bases are one or more of H 2 NR 20 , HNR 20 R 21 , NR 20 R 21 R 22 , and/or a salt thereof, wherein each R 20 , R 21 , and R 22 are independently C 1-8 alkyl optionally substituted with one or more —OH.
10. The pharmaceutical composition of claim 1 , wherein the one or more Bronsted bases are tris(hydroxymethyl)aminomethane, meglumine, and/or a tris(hydroxymethyl)aminomethane salt.
11. The pharmaceutical composition of claim 1 , wherein the molar ratio of Formula I to the one or more Bronsted bases is at least 1:2.
12. The pharmaceutical composition of claim 2 , wherein the aqueous solution is sterile water for injection, a sterile solution comprising dextrose, a sterile solution comprising sodium chloride, a sterile solution comprising benzyl alcohol, or Lactated Ringer's.
13. The pharmaceutical composition of claim 2 , wherein the aqueous solution is sterile water for injection or 0.9% sodium chloride injection.
14. The pharmaceutical composition of claim 2 , wherein the pharmaceutical composition is for injection intravenously.
15. A method of making the pharmaceutical composition of claim 1 , wherein the method comprises admixing Formula I and an amine and/or a salt thereof.