Studies on design and evaluation of controlled release colon targeted formulations of indomethacin

Abstract

The aim of the present study was to design and develop matrix-embedded formulations for colon specific delivery of indomethacin for the potential treatment of colorectal cancer. Indomethacin, a non-steroidal anti-inflammatory drug, commonly indicated in the treatment of osteo and rheumatoid arthritis, has shown good potential as an anti cancer agent against colorectal cancer. Therefore, a colon targeted formulation of indomethacin will ensure high local concentrations of drug in colon and reduce upper gastrointestinal and systemic toxicities that arise from the use of its conventional formulations. newline For the purpose of formulation design, a novel matrix system that would combine the advantages of pH and transit time controlled systems and overcome the problems associated with coated systems was proposed. It was expected that a dual polymer matrix embedded system comprising of a combination of time or swelling controlled and pH dependent polymers can offer a suitable means of achieving a pH and transit time dependent system that releases the drug in a bimodal (sigmoidal fashion). Therefore, the primary objective of the study was to investigate the effect of pH sensitive polymers in a matrix base individually and in combination with other polymers (hydrophilic and hydrophobic) to develop delayed release pH and time controlled formulations. For this purpose, the formulations were designed as single-unit (tablet) and multi unit (microsphere) based systems. Single matrix embedded tablet formulations were prepared by wet granulation technique and microspheres were prepared by oil/ oil solvent evaporation technique. The prepared tablet formulations were characterized for physical characteristics, in vitro drug release, release kinetics, batch reproducibility and stability on storage while the microparticles were characterized for particle size, physical characteristics, in vitro release, batch reproducibility and stability on storage.