Development of stable formulations of pemetrexed

This research has developed an improved lyophilized formulation for Pemetrexed to enhance its stability using various techniques such as amino acids, boric acid, and sugars. The preliminary screening identified sorbitol as the most suitable sugar and L-Arginine as most suitable amino acid due to low degradation rate and minimal change in reconstitution time after one month of storage under accelerated stability conditions. 32 factorial design was employed to optimize the formulation, considering the drug-to-boric acid ratio (X1 factor) and the drug-to-L-Arginine ratio (X2 factor). The Design-Expert® software was utilized to generate optimized formula based on the results of nine batches. The desired responses included the % assay of the lyophilized and reconstituted formulations, reconstitution time, and pH of the composition. The optimized batch exhibited results in-line with the software predictions. Stability testing of the optimized batch under accelerated conditions (for six months revealed no significant differences in the evaluation parameters. Furthermore, the optimized formulation outperformed the marketed formulation. Cell line studies conducted on Pemetrexed API and the formulated dosage form demonstrated enhanced efficacy of the formulation, indicated by a lower IC50 value compared to Pemetrexed API alone. These comprehensive studies confirmed the stability of the prepared dosage form.