OPTIMIZATION OF COMPONENT VARIABLES FOR SELF MICRO EMULSIFYING DRUG DELIVERY SYSTEMS BY USING EXTREME VERTICES MIXTURE DESIGNS

Abstract

Self-micro emulsifying drug delivery systems (SMEDDS) are the isotropic mixtures of natural or synthetic oils, solid or liquid surfactants, and hydrophilic co-solvents/surfactants that have a unique ability of forming fine oil-in-water (o/w) micro emulsions upon mild agitation followed by dilution in aqueous media, such as GI fluids. These were developed to overcome problems like low solubility and oral bioavailability associated with the delivery of Candesartan Cilexetil (CSC), a poorly water-soluble Angiotensin receptor blocker. Solubility of CSC in oily phases and surfactants was determined to identify components of SMEDDS. The composition of optimized formulation was Carbitol (50%), Cremophore EL (20%), Propylene Glycol (30%) and CSC (40 mg) as oil, surfactant, Co surfactant and drug, respectively. Extreme Vertices Mixture design was employed to optimize the formulations and the final formulation was optimized by utilizing desirability function approach. The globule size of optimized formulation was found to be approximately 47 nm which was not affected by the pH of dilution medium. The optimized SMEDDS released CSC approximately 90 % irrespective of the pH of dissolution medium. The present study ratified the use of principles of quality by design in optimization of pharmaceutical formulations.