Formulation Development and Evaluation of Microparticulate Drug Delivery System for Sustained Release of Anticancer Drugs

Abstract

Objective: The present study was planned with an objective of formulating sustained release microparticles of two anticancer drugs Gefitinib and Erlotinib HCl using biodegradable polymers. It was projected that such formulations would be able to prolong the drug release of both these water insoluble drugs for a longer duration to improve the drug therapy. Methods: PLGA based microparticles were prepared for loading Gefitinib by emulsion solvent evaporation method where the critical factors were optimized by a 32-factorial design. The second anticancer drug was erlotinib HCl (ERL) was encapsulated in polycaprolactone (PCL) and formulated as microparticles so as to sustain the release. Quality by design (QbD) elements were pragmatic in optimizing the critical parameters. Spray drying technique was used in development of microparticles. Anticancer efficacy was judged by the cytotoxicity studies using the L132 lung cancer cells and A549 cells on GEF-PLGA MPs and ERL-PCL MPs respectively. newlineResults: The mean particle size of GEF-PLGA MPs was in the range of 7.4±2.5 and#956;m and entrapment efficiency was found to be 80%. Scanning electron microscopy studies confirmed the spherical smooth shape. The optimized GEF-PLGA-MPs were able to sustained the release of gefitinib for 72 hours. The mechanism of drug release was first-order kinetics and followed Fickian diffusion. MTT assay showed 3-fold enhanced cytotoxicity of GEF loaded microparticles against L132 cells as compared to plain GEF. Box-Behnken design optimized the mean particle size (5 and#956;m), drug encapsulation efficiency of more than 85% and a sustained release duration of 1 week. The IC50 values studied on A549 cells obtained by the MTT assay was 30.11 ± 1.3 and#956;M on day 1 for the ERL-PCL-MP-14 which got further reduced to 15.7 ± 1.5and#956;M on 3rd day. Plain drug did not show the sustained release after 1 day hence indicating a much superior anticancer efficacy. Stability studies confirmed that both the optimized newlineformulations of GEF-PLGA MPs and ERL-PCL-MPs were stable at 2-5ºC