Claims for Patent: 11,147,817

Summary for Patent: 11,147,817

Title:	Pharmaceutical composition of pemetrexed
Abstract:	The present invention relates to pharmaceutical composition comprising pemetrexed, a ready to use injection comprising pemetrexed. Liquid composition of pemetrexed comprises head space oxygen less than 5%, dissolved oxygen less than 2 ppm and individual impurity level less than 0.2%.
Inventor(s):	Jayanta Kumar Mandal, Sandip Pareshbhai Mehta
Assignee:	FTF Pharma Pvt Ltd
Application Number:	US17/127,278
Patent Claims:	1. A liquid composition comprising: (a) 5 mg/mL to 100 mg/mL of pemetrexed, or its pharmaceutically acceptable salts; (b) L-cysteine, or salt thereof; (c) a pharmaceutically acceptable excipient; (d) less than 5% v/v of head space oxygen; (e) less than 2 parts per million (ppm) of dissolved oxygen; and (f) less than 1% w/w total impurities, wherein said liquid composition does not contain a chelating agent; and wherein the total impurities remain at less than 1% w/w for at least one month when stored at room temperature. 2. The liquid composition of claim 1, wherein the pharmaceutically acceptable excipient is selected from the group consisting of an osmolarity adjusting agent, a stabilizing agent, a pH adjusting agent, a vehicle, and combinations thereof. 3. The liquid composition of claim 1, wherein the chelating agent is selected from the group consisting of ethylene diamine tetraacetic acid or a salt thereof, diethylene triamine pentaacetic acid or a salt thereof, calteridol or a salt thereof, and combinations thereof. 4. The liquid composition of claim 3, wherein the composition is prepared using a process of terminal sterilization. 5. The liquid composition of claim 4, wherein said terminal sterilization is steam sterilization with an F0 value of from 1 minute to 30 minutes. 6. The liquid composition of claim 1, wherein the composition comprises less than 0.5% w/w total impurities. 7. A liquid composition comprising: (a) about 10 mg/mL of pemetrexed; (b) about 1 mg/mL of L-cysteine hydrochloride; (c) a pharmaceutically acceptable excipient; (d) less than 5% v/v of head space oxygen; (e) less than 2 parts per million (ppm) of dissolved oxygen; and (f) less than 1% w/w total impurities, wherein said liquid composition does not contain a chelating agent; and wherein the total impurities remain at less than 1% w/w for at least one month when stored at room temperature. 8. The liquid composition of claim 7, wherein the pharmaceutically acceptable excipient is selected from the group consisting of an osmolarity adjusting agent, a stabilizing agent, a pH adjusting agent, a vehicle, and combinations thereof. 9. The liquid composition of claim 7, wherein said chelating agent is selected from the group consisting of ethylene diamine tetraacetic acid or a salt thereof, diethylene triamine pentaacetic acid or a salt thereof, calteridol or a salt thereof, and combinations thereof. 10. The liquid composition of claim 7, wherein the composition comprises less than 0.5% w/w total impurities. 11. A process for preparing the liquid composition of claim 1, comprising: (a) preparing a solution mixture comprising: (i) 5 mg/mL to 100 mg/mL of pemetrexed or its pharmaceutically acceptable salts, (ii) L-cysteine or salt thereof; (iii) a pharmaceutically acceptable excipient; and (iv) less than 1% w/w total impurities, under conditions to maintain dissolved oxygen level of 2 parts per million (ppm) or less; and (b) filtering and filling a vial with the solution of step (a) and maintaining head space oxygen of less than 5% v/v to produce the liquid composition. 12. The process of claim 11, further comprising the step of sterilizing the filtered solution by steam sterilization with an F0 value of from 1 minute to 30 minutes. 13. The process of claim 11, wherein the solution mixture comprises less than 0.5% w/w total impurities. 14. The liquid composition of claim 1, wherein the pH of the composition is between 6 and 8. 15. The liquid composition of claim 14, wherein the pH of the composition is about 7.4. 16. The liquid composition of claim 7, wherein the pH of the composition is between 6 and 8. 17. A liquid composition comprising: (a) 5 mg/mL to 100 mg/mL of pemetrexed, or its pharmaceutically acceptable salts; (b) L-cysteine, or salt thereof; (c) a pharmaceutically acceptable excipient; (d) less than 5% v/v of head space oxygen; (e) less than 2 parts per million (ppm) of dissolved oxygen; and less than 1% w/w total impurities, wherein said liquid composition does not contain a chelating agent; and wherein said liquid composition is stable for at least one month when stored at room temperature. 18. A liquid composition comprising: (a) about 10 mg/mL of pemetrexed; (b) about 1 mg/mL of L-cysteine hydrochloride; (c) a pharmaceutically acceptable excipient; (d) less than 5% v/v of head space oxygen; (e) less than 2 parts per million (ppm) of dissolved oxygen; and (f) less than 1% w/w total impurities, wherein said liquid composition does not contain a chelating agent; and wherein said liquid composition is stable for at least one month when stored at room temperature.