Olmesartan medoxomil (OLM) is an angiotensin II receptor blocker (ARB) antihypertensive agent administered orally that has absolute bioavailability of only 26% due to the poor aqueous solubility (7.75？μg/ml). The aim of the present investigation was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral absorption of OLM. The solubility of OLM in various oils, surfactants, and cosurfactants was determined. Pseudoternary phase diagrams were constructed using Acrysol EL 135, Tween 80, Transcutol P, and distilled water to identify the efficient self-microemulsification region. Prepared SMEDDS was further evaluated for its emulsification time, drug content, optical clarity, droplet size, zeta potential, in vitro dissolution, and in vitro and ex vivo drug diffusion study. The optimized formulation S2 contained OLM (20？mg), Tween 80 (33%v/v), Transcutol P (33%v/v), and Acrysol EL 135 (34%v/v) had shown the smallest particle size, maximum solubility, less emulsification time, good optical clarity, and in vitro release. The in vitro and ex vivo diffusion rate of the drug from the SMEDDS was significantly higher than that of the plain drug suspension. It was concluded that SMEDDS would be a promising drug delivery system for poorly water-soluble drugs by the oral route. 1. Introduction Approximately, 40% of the new drug candidates in development today are water insoluble and associated with poor bioavailability. There were various formulation approaches reported to overcome these problems; these include the use of drug nanoparticles, solid dispersions, micronization, lipids, surfactants, complexation with cyclodextrin, and permeation enhancers [1]. Majority of these approaches have their limitations because of the need for specialized equipment, complicated manufacturing process, longer processing time, and regulatory complexity. Lipid-based formulation approaches, particularly the self-microemulsifying drug delivery system (SMEDDS), are well known for their potential as alternative approach for delivery of hydrophobic drugs [2], which are associated with poor water solubility and low oral bioavailability [3–5]. Lipid-based drug delivery system has gained considerable interest after the commercial success of Norvir (ritonavir), Fotovase (saquinavir), and Neoral (cyclosporine A). Olmesartan medoxomil is a novel selective angiotensin II receptor blocker that is approved for the treatment of hypertension. It is a prodrug that is rapidly deesterified during absorption from the gastrointestinal tract to produce an active metabolite,
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