FORMULATION AND EVALUATION OF SOLID SELF EMULSIFYING DRUG DELIVERY SYTEM OF RANOLAZINE

INTRODUCTION The improvement of bio-availability of drugs presents one of the greatest challenges in drug formulations. Various techniques have been utilized to increase drug solubility and dissolution of poorly water soluble drugs exhibiting dissolution rate limited absorption. Among these, self-emulsifying formulations are one of the options to improve the bioavailability of poorly soluble drugs. SEDDS are thermodynamically stable, high solubilization capacity, improvement in bioavailability. These are isotropic mixtures of oil, surfactant, and co-surfactant. These formulations when diluted in aqueous medium with gentle agitation disperse spontaneously to form fine oil in water emulsion. The rate and extent of absorption of poorly water soluble drug incorporated in self-emulsifying formulations increases due to the presence of drug in soluble form in the gastro intestinal tract offering a large surface area for absorption . The oral bioavailability augmentation is achieved by enhanced dissolution and solubilization of the administered drug by stimulation of biliary and pancreatic secretions, prolongation of gastric residence time . Many techniques are offered to convert conventional liquid SEDDS to solid such as adsorption to solid carriers, spray drying, spray cooling, melt extrusion, supercritical fluid based methods, etc. But among these, the adsorption technique is simple and just involves addition of liquid formulation onto carriers by mixing in a blender. The resulting powder may then be filled directly into capsules or, alternatively, mixed with excipients before compression into tablets. A significant benefit of the adsorption technique is good content uniformity . Ranolazine, an anti anginal drug, used in the treatment of various cardiovascular diseases, belongs to class II in biochemical classification system i.e. low solubility and high permeability. One of the major problems with this drug is its low solubility in biological fluids, which results in poor oral bioavailability. Poor solubility of ranolazine leads to poor dissolution and hence variation in bioavailability. Thus increasing the aqueous solubility and dissolution of ranolazine is of therapeutic importance. Aqueous solubility and dissolution of ranolazine can be increased by formulating in SEDDS. Hence main objective of the study was to develop and evaluate an optimal S-SEDDS formulation of the drug. The Objective of present study was to develop a solid self-emulsifying drug delivery system (SEDDS) of ranolazine to enhance its oral bioavailability. Ranolazine is an anti anginal drug used in the treatment of cardiovascular diseases like chronic angina, ischemia. Solubility of ranolazine in various oils was determined to optimize the oil phase of a SEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseudo ternary phase diagrams were constructed to identify the self emulsification region. Liquid SEDDS were prepared using Oleic acid, Cremophor EL and Transcutol P as oil, surfactant and co-surfactant respectively. Solid SEDDS were prepared using Aerosil 200 as an adsorbent. Solid systems were preferred to SEDDS as they are stable, easy to handle and have improved patient compliance. Prepared Solid systems were evaluated for flow properties, drug content and in-vitro drug release. Results showed that prepared Solid systems have good flow property with 97.33% drug content. Dilution study by visual observation showed that there was spontaneous micro emulsification and no sign of phase separation. SEM photograph showed smooth surface of Solid system with no aggregation. Drug release from Solid systems was found to be significantly higher compared to conventional solid dosage form. From the present study it is clear that SEDDS can be formulated to improve the dissolution and oral bioavailability of poorly water soluble drug, ranolazine.