¹Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra, India DOI : 10.29228/jrp.9 Dapsone is a class II BCS with antibacterial and anti-inflammatory action. The goal of this study was to devise a dapsone (DP) system of solid self-microemulsifying drug delivery (S-SMEDDS). Various proportions of capryol 90 as an oil form, tween 80 as a surfactant and Labrasol as a co-surfactant were selected to prepare a pseudo ternary diagram for the self-microemulsifying drug delivery system (L-SMEDDS). The optimized formulation of LSMEDDS (F8) containing capryol 90 (10 percent w/w), Tween 80 (67.5/5 w/w), and labrasol (22.5 percent w/w) showed the smallest particle size, less emulsification time, high optical clarity, in-vitro release and improved ex-vivo permeation. L-SMEDDDS was converted to S-SMEDDS by adsorbing on neusilin US2 and spray drying with aerosil 200. The effect of inlet temperature (A), feed flow rate (B) and carrier concentration (C) on particle size (Y1) and % practical yield (Y2) was studied using Box-Behnken design. Using the results of dependent variables, polynomial equations, surface response plots, and contour plots were developed. S-SMEDDS have been tested for flow properties, drug quality, reconstitution properties, DSC, XRD, SEM, drug release in vitro and anti-inflammatory activity in vivo. The present study showed the applicability of design of experiments (DOE) to optimize the process parameters needed to produce DP S-SMEDDS as an effective approach to improving its solubility. Keywords : Self micro-emulsifying drug delivery system; labrasol; capryol 90; Box-Behnken design; neusilin US2