In the present investigation an attempt was made to enhance the solubility and dissolution of poorly soluble drug, isotretinoin, by formulating self-nanoemulsifying drug delivery system (SNEDDS). Liquid SNEDDSs were prepared using Transcutol P as oil, Tween 80 as surfactant, and PEG 400 as cosurfactant. Pseudoternary phase diagrams were constructed to identify the efficient self-nanoemulsification region. The formulation with 40% oil (Transcutol P) and 60% surfactant: cosurfactant (Tween 80: PEG 400) ratio of 1？:？1 was optimized based on evaluation parameters for droplet size analysis, self-emulsification capacity, zeta potential, and in vitro drug release performance. The optimized system contains mean droplet size of 36.60？nm and zeta potential (ζ) ？26.73？mV. The optimized formulation A1 was adsorbed onto Fujicalin to produce solid SNEDDS, which exhibited good flow properties and preserved the self-emulsification properties of liquid SNEDDS. The differential scanning calorimetry, FT-IR studies of solid SNEDDS revealed transformation of isotretinoin into molecularly dissolved state in the liquid SNEDDS. In vitro dissolution profiles showed that dissolution rate of ISN from solid SNEDDS was significantly greater as compared to pure drug. 1. Introduction Many drug candidates show low water solubility and hence might have a problem of bioavailability, intrasubject or intersubject variability, and lack of dose proportionality [1]. Thus the oral delivery of these low soluble drugs is difficult where dissolution is rate limiting step [2]. The various strategies such as solid dispersions [3], complexation with cyclodextrin [4] and lipid based formulations [5], and self-emulsifying drug delivery systems (SEDDS) [6] have been reported in the literature. Of various strategies reported SEDDS are found to be the prominent approach to improve solubility. SEDDS improve the oral bioavailability of poorly soluble drugs by improving the solubility and maintaining the drug in a dissolved state, in small droplets of oil, all over its transport through the gastrointestinal tract [7]. SEDDS is an isotropic mixture that is comprise of drug, oil, surfactant, and cosurfactant. It readily dispersed in the aqueous environment of the gastrointestinal tract and forms a fine oil-in-water emulsion. If the droplet size of SEDDS is less than 100？nm it is self-nanoemulsifying (SNEDDS) and for less than 5？ m it is self-microemulsifying (SMEDDS) under gentle agitation which improves the oral bioavailability of poorly water-soluble drugs. Compared to ordinary metastable emulsions, SNEDDS
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