Application of Box-Behnken design in understanding the quality of genistein self-nanoemulsified drug delivery systems and optimizing its formulation

The purpose of the present study was to understand the effect of formulation variables of self- nanoemulsified drug delivery systems (SNEDDS) on the rapid dissolution of a model drug, genistein (GN). A three-factor, three-level Box-Behnken design was used to explore the main and interaction effect of several independent formulation variables including the amount of Maisine 35-1 and Labrafac Lipophile WL 1349 (1:1, w/w) (X₁), Cremophor EL and Labrasol (3:1, w/w) (X₂), and Transcutol P (X₃). Droplet size (Y₁), turbidity (Y₂), and dissolution percentage of GN after 5 (Y₃) and 30 (Y₄) min were the dependent variables. A mathematical relationship, Y₃?=???89.3447?+?5.9524X₁?+?1.0683X₂?+?0.462X₃???0.0825X₁²???0.0075X₂²???0.0009X₃²?+?0.0104X₁X₂ ??0.0113X₁X₃?+?0.0009X₂X₃ (r2?=?0.9604), was obtained to explain the effect of all factors and their co-linearities on the dissolution of GN at 5?min. Formulation optimization was then performed to maximize dissolution percentage of GN at 5?min (Y₃). The optimized formulation was predicted to dissolution 93.34% of GN at 5?min, when X₁, X₂ and X₃ values were 37.1, 101.7 and 77.3?mg, respectively. A new batch was prepared according to the optimized formulation, and the observed and predicted values of Y₃ were in close agreement. In conclusion, the Box-Behnken experimental design allowed us to understand the effect of formulation variables on the rapid dissolution of GN from SNEDDS, and optimize the formulation to obtain a rapid drug dissolution at 5?min.