Preparation and in-vitro evaluation of self emulsifying drug delivery system of antihypertensive drug valsartan

The present study deals with formulation of a valsartan based Self emulsifying drug delivery system of a poorly water soluble drug. SEDDS are the isotropic mixtures of oil, surfactant, co surfactant and drug that form oil in water microemulsion when introduced into aqueous phase under gentle agitation. The present research work describes a Self Emulsifying Drug Delivery System (SEDDS) of valsartan using Castor oil, Tween-80, PEG-600. Valsartan is an angiotensin converting enzyme (ACE) inhibitor with limited water solubility, which accounts for a low and variable oral bioavailability (19-25%). Hence, the main objective of study was to formulate SEDDS of valsartan in order to achieve a better dissolution rate which would further help in enhancing oral bioavailability. Pseudo-ternary phase diagrams were plotted to check for the micro-emulsification range and also to evaluate the effect of valsartan on the emulsification behavior of the phases. The mixtures consisting of oil (castor oil) with surfactant (tween 80), co-surfactant (PEG 600) were found to be optimum formulations. Prepared SEDDS formulations were tested for microemulsifying properties and the resultant microemulsions were evaluated for robustness to dilution, assessment of efficiency of self emulsication, emulsification time, turbidity measurment, viscosity, drug content and in-vitro dissolution. The optimized SEDDS formulation further evaluated for heating cooling cycle, centrifugation studies and freeze thaw cycling, particle size distribution, zeta potential were carried out to confirm the stability of the formed SEDDS. The formulation was found to show a significant improvement in terms of the drug release with complete release of drug within 60 minutes. Thus, Self microemulsifying formulation of valsartan was successfully developed. Key-Words: Self Emulsifying Drug Delivery System, Valsartan, Bioavailability Introduction The oral route is the preferred route for chronic drug therapy. Numerous potent lipophilic drugs exhibit low oral bioavailability due to their poor aqueous solubility properties. For this class of compound defined as “low solubility/ high permeability class II, dissolution in the environmental lumen is the rate controlling step in the absorption process. Efforts are ongoing to enhance oral bioavailability of lipophilic drug in order to increase their clinical efficacy 1 . In recent years, the formulation of poorly soluble compounds presented interesting challenges for formulation scientists in the pharmaceutical industry. Up to 40% of new chemical entities discovered by the pharmaceutical industry are poorly soluble or lipophilic compounds, which leads to poor oral bioavailability, high intraand inter-subject variability, and lack of dose proportionality. * Corresponding Author To triumph over these problems, various formulation strategies are exploited such as use of surfactants, lipids, permeation enhancers, micronisation, salt formation, cyclodextrins, nanoparticles and solid dispersions. Each and every method for bioavailability enhancement is having its own merits and demerits. In salt formation, the salts that are formed may convert back to their original acid or base forms and lead to aggregation in the gastro-intestinal-tract (GIT). Particle size reduction may not be desirable in situations where handling difficulties and poor wettability are experienced for very fine powders. For compounds in which the primary limitation to absorption is poor aqueous solubility and slow dissolution rate, where intestinal permeability is not a limiting factor, (e.g., BCS Type II drugs) and for which conventional formulation approaches (e.g. salt or crystal form selection, particle size reduction, solid dispersions or the addition of surfactants) have failed, a lipid-based Research Article [Gupta et al., 2(3): March, 2011]