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. A liquid pharmaceutical composition, consisting of:
20 mg/mL to 30 mg/mL of pemetrexed diacid;
200 mg/mL to 300 mg/mL of propylene glycol;
12 mg/mL to 24 mg/mL of tromethamine;
optionally HCl; and
water,
wherein the pH of the composition is from about 7.4 to 7.6, wherein the composition is suitable for multi-dose administration, and wherein the composition remains stable when stored for about 14 months at a temperature of 2° C. to 8° C. in a container having a head-space oxygen content of about 20% v/v, such that the composition comprises no more than 3% w/w of total impurities after said storage.
2. The liquid pharmaceutical composition of claim 1 , consisting of:
25 mg/mL of the pemetrexed diacid;
250 mg/mL to 300 mg/mL of the propylene glycol;
17 mg/mL to 21 mg/mL of the tromethamine;
optionally HCl; and
water,
wherein the pH of the composition is from about 7.4 to 7.6.
3. The liquid pharmaceutical composition of claim 1 , consisting of:
25 mg/mL of the pemetrexed diacid;
250 mg/mL to 300 mg/mL of the propylene glycol;
18 mg/mL to 20 mg/mL of the tromethamine;
optionally HCl; and
water,
wherein the pH of the composition is from about 7.4 to 7.6.
4. A vial containing a liquid pharmaceutical composition consisting of:
20 mg/mL to 30 mg/mL of pemetrexed diacid;
200 mg/mL to 300 mg/mL of propylene glycol;
12 mg/mL to 24 mg/mL of tromethamine;
optionally HCl; and
water,
wherein the pH of the composition is from about 7.4 to 7.6, wherein the composition remains stable when stored for about 14 months at a temperature of 2° C. to 8° C. in a container having a head-space oxygen content of about 20% v/v, such that the composition comprises no more than 3% w/w of total impurities after said storage.
5. The vial of claim 4 , wherein the vial is a multi-dose vial.
6. The vial of claim 4 , wherein the vial contains:
25 mg/mL of the pemetrexed diacid;
250 mg/mL to 300 mg/mL of the propylene glycol; and
17 mg/mL to 21 mg/mL of the tromethamine.
7. The vial of claim 6 , wherein the vial is a multi-dose vial.
8. The vial of claim 4 , wherein the vial contains:
25 mg/mL of the pemetrexed diacid;
250 mg/mL to 300 mg/mL of the propylene glycol; and
18 mg/mL to 20 mg/mL of the tromethamine.
9. The vial of claim 8 , wherein the vial is a multi-dose vial.