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Preparation and physicochemical properties of crystalline forms and amorphous pemetrexed disodium

Olga M. Michalak ,  Kamil Jatczak ,  Anna B. Witkowska ,  Marta Łaszcz ,  Wiesław Pucko ,  Iwona Bujak ,  Aleksandra Groman 

Pharmaceutical Research Institute, Rydygiera 8, Warsaw 01-793, Poland

The commercial product pemetrexed disodium, a known anticancer drug, is used for the treatment of locally advanced or metastatic non-small-cell lung cancer (NSCLC).

Two hydrate forms heptahydrate and hemipentahydrate as well as amorphous pemetrexed disodium are currently well established in the literature. The heptahydrate form is used in marketed products.
We have developed processes for preparation of hemipentahydrate form and amorphous pemetrexed disodium. These developed processes are in compliance with the purity requirements for an active substance used in a medicinal product.
Two approaches for the preparation of pemetrexed disodium were used. In the first approach, hydrolysis of diethyl ester in aqueous sodium hydroxide solution led to hemipentahydrate form. In the second approach, deprotonation of pemetrexed diacid in the presence of sodium methoxide in the anhydrous conditions gave amorphous pemetrexed disodium.

The physicochemical characterization of crystalline forms and amorphous pemetrexed disodium as well as  starting materials and process-related impurities was accomplished using various analytical methods (IR, NMR, XRPD, DSC, TG).


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Presentation: Poster at IX Multidyscyplinarna Konferencja Nauki o Leku, by Olga M. Michalak
See On-line Journal of IX Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2014-03-13 14:55
Revised:   2014-05-02 13:04