PEMETREXED FORMULATIONS
The present invention is directed to pemetrexed formulations comprising a non-aqueous solvent that remains stable after dilution for at least about 48 hours when stored at 2° C. to 8° C. The present invention is also directed to pemetrexed formulations comprising a non-aqueous solvent that remains stable for at least about 24 months when stored at 2° C. to 8° C.
1 - 30 . (canceled)
31 . A liquid pharmaceutical composition comprising:
pemetrexed at a concentration of about 20 mg/mL to about 30 mg/mL;
at least about 13 mg/mL of citric acid;
thioglycerol;
methionine;
water; and
optionally HCl,
wherein the composition comprises at least 90% of said pemetrexed concentration after storage at a temperature of 2° C. to 8° C. for at least 12 months.
32 . The liquid pharmaceutical composition of claim 31 , comprising pemetrexed at a concentration of about 25 mg/mL.
33 . The liquid pharmaceutical composition of claim 31 , wherein the pemetrexed is pemetrexed diacid, pemetrexed monoacid, a pharmaceutically acceptable salt of pemetrexed, or a combination thereof.
34 . The liquid pharmaceutical composition of claim 31 , wherein the pemetrexed is pemetrexed disodium.
35 . The liquid pharmaceutical composition of claim 31 , wherein the concentration of the citric acid is about 13 mg/mL.
36 . The liquid pharmaceutical composition of claim 31 , wherein the pH of the composition is from about 7.4 to about 7.6.
37 . The liquid pharmaceutical composition of claim 31 , wherein the pH of the composition is 7.4.
38 . The liquid pharmaceutical composition of claim 31 , wherein the pH of the composition is 7.5.
39 . The liquid pharmaceutical composition of claim 31 , wherein the pH of the composition is 7.6.
40 . The liquid pharmaceutical composition of claim 31 , wherein the composition is stored in a vial with a headspace oxygen concentration of about 20 v/v %.
41 . The liquid pharmaceutical composition of claim 31 , wherein the composition comprises at least 90% of said pemetrexed concentration after storage at a temperature of 2° C. to 8° C. for at least 18 months.
42 . The liquid pharmaceutical composition of claim 31 , wherein the composition comprises no more than about 8% w/w total impurities after storing the composition at a temperature of 2° C. to 8° C. for at least 12 months.
43 . A liquid pharmaceutical composition consisting essentially of:
pemetrexed at a concentration of about 20 mg/mL to about 30 mg/mL;
at least about 13 mg/mL of citric acid;
thioglycerol;
methionine;
water; and
optionally HCl,
wherein the composition comprises at least 90% of said pemetrexed concentration after storage at a temperature of 2° C. to 8° C. for at least 12 months.
44 . A liquid pharmaceutical composition consisting of:
pemetrexed at a concentration of about 20 mg/mL to about 30 mg/mL;
at least about 13 mg/mL of citric acid;
thioglycerol;
methionine;
water; and
optionally HCl,
wherein the composition comprises at least 90% of said pemetrexed concentration after storage at a temperature of 2° C. to 8° C. for at least 12 months.
45 . A method of treating pleural mesothelioma or non-squamous, non-small cell lung cancer in a patient in need thereof comprising:
providing the liquid pharmaceutical composition of claim 31 ;
diluting the liquid pharmaceutical composition with a pharmaceutically acceptable diluent to form a diluted liquid composition having a diluted pemetrexed concentration; and
intravenously administering the diluted liquid composition to the patient.
46 . The method of claim 45 , wherein the pharmaceutically acceptable diluent is selected from the group consisting of saline, water for injection, 5% dextrose in water, Ringer's Injection, and Lactated Ringer's Injection.
47 . The method of claim 45 , wherein the diluent is saline.
48 . The method of claim 45 , wherein the diluted liquid composition comprises at least 90% of said diluted pemetrexed concentration after storage at a temperature of 2° C. to 8° C. for at least 12 hours.
49 . The method of claim 45 , wherein the diluted liquid composition comprises at least 90% of said diluted pemetrexed concentration after storage at a temperature of 2° C. to 8° C. for at least 24 hours.
50 . The method of claim 45 , wherein the diluted liquid composition comprises at least 90% of said diluted pemetrexed concentration after storage at a temperature of 2° C. to 8° C. for at least 48 hours.