Formulation and In-vitro Characterization of Self Nano-emulsifying Drug Delivery System (SNEDDS) for enhanced Solubility of Candesartan Cilexetil

摘要

Candesartan cilexetil is the prodrug of candesartan, a selective angiotensin II receptor antagonist, used in the management of hypertension and heart failure. It is characterized by poor aqueous solubility resulting in low bioavailability. Self-nanoemulsifying drug delivery systems (SNEDDS) loaded with candesartan cilexetil were successfully developed to overcome such obstacles. Preliminary screening was carried out to select proper oil, surfactant and co-surfactant combination for successful SNEDDS formulation. Ternary and pseudo ternary diagrams were constructed to optimize the system. Capryol 90? as an oil showed high emulsification ability. The nature of obtained dispersions was found to be nanoemulsions. Six formulations were visually inspected and evaluated for stability, robustness to dilution, effect of drug loading on the nano-emulsion boundary, viscosity, content uniformity, their mean droplet size, polydispersity index (PDI), zeta potential in addition to in vitro drug release study. Three formulations showed a very short emulsification time of less than 3minutes. The emulsification efficiency was significantly superior at pH6.8. All selected formulations showed mean droplet size (124.25 to 460.15nm), very low PDI values (0.311-0.562) and zeta potential (30.5-44.45 mV). Formulation F16 (10% w/w Capryol 90?, 30% w/w Tween80, 60% w/w Transcutol?) was- selected for further characterization. Droplet size of F16 showed robustness to different dilution folds with different media. These results indicate that, SNEDDS could be promising delivery systems with a rapid onset of action and prolonged therapeutic effect of candesartan cilexetil.