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The aim of this study was to systematically obtain a model of factors that would yield an optimized self-nanoemulsified capsule dosage form (SNCDF) of a highly lipophilic model compound, Coenzyme Q10 (CoQ). Independent variables such as amount of R-(+)-limonene (X1), surfactant (X2), and cosurfactant (X3), were optimized using a 3-factor, 3-level Box-Behnken statistical design. The dependent variables selected were cumulative percentage of drug released after 5 minutes (Y1) with constraints on drug release in 15 minutes (Y2), turbidity (Y3), particle size (Y4), and zeta potential (Y5). A mathematical relationship obtained,Y1=78.503+6.058X1 +13.738X2+5.986X3−25.831X12+9.12X1X2−26.03X1X3−38.67X22 +11.02X2X3−15.55X33 (r2=0.97), explained the main and quadratic effects, and the interaction of factors that affected the drug release. Response surface methodology (RSM) predicted the levels of factorsX1,X2, andX3 (0.0344, 0.216, and 0.240, respectively), for a maximized response ofY1 with constraints of >90% release onY2. The observed and predicted values ofY1 were in close agreement. In conclusion, the Box-Behnken experimental design allowed us to obtain SNCDF with rapid (>90%) drug release within 5 minutes with desirable properties of low turbidity and particle size.