Response surface methodology for optimization and characterization of limonene-based Coenzyme Q10 self-nanoemulsified capsule dosage form

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 (X-1), surfactant (X-2), and cosurfactant (X-3), 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 (Y-1) with constraints on drug release in 15 minutes (Y-2), turbidity (Y-3), particle size (Y-4), and zeta potential (Y-5). A mathematical relationship obtained, Y-1 = 78.503 + 6.058X(1) + 13.738X(2) + 5.986X(3) - 25.831X(1)(2) + 9.12X(1)X(2) - 26.03 X1X3 - 38.67 X-2(2) + 11.02X(2)X(3) - 15.55 X-3(3) (r(2) = 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 factors X-1, X-2, and X-3 (0.0344, 0.216, and 0.240, respectively), for a maximized response of Y-1 with constraints of >90% release on Y-2. The observed and predicted values of Y-1 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.