Influence of various bridging liquids on spherical agglomeration of indomethacin

Abstract

For poorly soluble, highly permeable (Class II) drugs, such as Indomethacin, the rate of oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Therefore together with the permeability, the solubility and dissolution behaviour of a drug are key determinants of its oral bioavailability. Indomethacin is an anti- inflammatory drug that is characterized by poor water solubility and flow properties. The main objective of the present study is to prepare spherical agglomerates of Indomethacin by using various bridging liquids and to study the effect of bridging liquids on micromeritic properties and dissolution behavior. Spherical agglomerates were prepared by using solvent change method. Solvent composition for spherical agglomeration was determined by constructing ternary diagram. Crystallization medium used for spherical agglomerates of Indomethacin were DMF (good solvent); water (poor solvent); chloroform/isopropyl acetate/dichloromethane (bridging liquids) in the ratio of 25:62.5:12.5 respectively. Spherical agglomerates were characterized by differential scanning calorimetry, IR spectroscopy, XRD and Scanning electron microscopy. Gas phase chromatography was carried to estimate the residual DMF, chloroform, isopropyl acetate and dichloromethane. Micromeritic and dissolution behavior studies were carried out. Process variables such as amount of bridging liquid were optimized. Dissolution profile of the spherical agglomerates was compared with commercial sample. Tablets were prepared using spherical agglomerates by direct compression and evaluated for tablet properties. Spherical agglomerates exhibited decreased crystallinity and improved micromeritic properties. The dissolution profiles of Indomethacin tablets prepared using spherical agglomerates exhibit greater dissolution behaviour than tablets prepared by powder raw material. Hence this technique can be used for formulation of tablets of Indomethacin by direct compression with directly compressible tablet excipients.