Stable lyophilized composition of pemetrexed dipotassium
AssigneeAVYXA Pharma
InventorsMukteeshwar Gande, Praveen Reddy Billa
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Abstract
The present invention relates to a stable, lyophilized pharmaceutical composition comprising pemetrexed dipotassium, mannitol, and a pH modifying component consisting essentially of hydrochloric acid. The composition is designed for ease of reconstitution and demonstrates long-term stability. Specifically, when stored in sealed and sterile vials at 25° C., the composition maintains its integrity for 12 months and more. Also, described here in the method of treating non-squamous NSCLC or mesothelioma using the composition of invention.
Claims16
A reconstitutable lyophilized pharmaceutical composition, comprising:
- pemetrexed dipotassium in an amount of about 118.3 mg equivalent to 100 mg of pemetrexed;
- and mannitol in an amount of about 106 mg;
- or
- pemetrexed dipotassium in an amount of about 591.5 mg equivalent to 500 mg pemetrexed;
- and mannitol in an amount of about 500 mg;
- and
- a pH modifying component consisting essentially of hydrochloric acid;
- with the proviso that the pH modifying component does not include a hydroxide base;
- wherein after storage for at least 12 months at 25° C., the composition comprises:
- not more than 2% w/w total water content;
- and
- not more than 0.6% w/w total impurities, including total degradation impurities wherein the degradation impurities are selected from:
- (a) Impurity-B in an amount that does not exceed 0.1% w/w;
- (b) Impurity-C in an amount that does not exceed 0.1% w/w;
- (c) Impurity-E in an amount that does not exceed 0.1% w/w;
- (d) ketopemetrexed in an amount that does not exceed 0.2% w/w;
- and
- a combination of two or more thereof.
A method of treating non-squamous NSCLC or mesothelioma to a patient in need thereof, comprising administering:
- (i) a reconstitutable lyophilized pharmaceutical composition comprising pemetrexed dipotassium in an amount of about 118.3 mg equivalent to 100 mg of pemetrexed;
- and mannitol in an amount of about 106 mg;
- or
- (ii) a reconstitutable lyophilized pharmaceutical composition comprising pemetrexed dipotassium in an amount of about 591.5 mg equivalent to 500 mg pemetrexed;
- and mannitol in an amount of about 500 mg;
- and
- a pH modifying component consisting essentially of hydrochloric acid;
- with the proviso that the pH modifying component does not include a hydroxide base;
- wherein after at least 12 months at a temperature of 25° C., the composition comprises:
- (a) not more than 1.2% w/w total impurities, of which total degradation impurities do not exceed 0.6% w/w;
- wherein the degradation impurities comprise impurity-E in an amount that does not exceed 0.1% w/w;
- and
- (b) not more than 2% w/w total water content.
Dependencies are inferred from the claim text.