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Abstract

FORMULATION AND EVALUATION OF PEMETREXED DISODIUM LOADED PLGA MICROSPHERES

Vanga Harish*, Budidi Krishna Geetha, Lohithasu D., Prashanth Kumar Killi and M. Mohan Varma

ABSTRACT

Objective: The objective of the present work was to formulate and evaluate controlled release Pemetrexed disodium microspheres for subcutaneous administration for treating pleural mesothelioma and non-small cell lung cancer effectively and also to improve patient compliance with fewer side effects. Pemetrexed is chemically similar to folic acid (L-Glutamic acid) and is in the class of chemotherapy drugs called folate antimetabolites. It works by inhibiting three enzymes used in purine and pyrimidine synthesis - thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells. Method: Different formulations were prepared by following solvent evaporation technique (double emulsion) using biodegradable poly(Lactide-co-Glycolide) acid and evaluated for percentage yield, entrapment efficiency, surface morphology (SEM), particle size analysis, in-vitro drug release and stability studies. Results: The prepared microspheres were white, free flowing and spherical in shape. The mean Particle size of the microspheres was found in the range of 26 to 206μm. The drug-loaded microspheres showed 87% of entrapment and release was extended up to 30 days releasing 95.6% of the total drug from the microspheres. The infrared spectra showed stable character of pemetrexed in the drug-loaded microspheres and revealed the absence of drug-polymer interactions. Scanning electron microscopy study revealed that the microspheres were spherical and porous in nature. Conclusion: The pemetrexed is uniformly distributed within the microspheres which are made of a biodegradable D, L-lactic and glycolic acids co-polymer. The optimized formulations of Pemetrexed disodium microspheres with controlled release were attempted for a release upto atleast one month.

Keywords: Bioavailability, Controlled release, Microspheres, Pemetrexed disodium, PLGA polymer, SEM, Subcutaneous.


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