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

作者：Zhu Saijie; Hong Minghuang; Liu Chen; Pei Yuanying^*

来源：Pharmaceutical Development and Technology, 2009, 14(6): 642-649.

DOI：10.3109/10837450902882385

• Box-Behnken design
• genistein
• self-nanoemulsified drug delivery systems
• dissolution
• optimization

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) (X(1)), Cremophor EL and Labrasol (3:1, w/w) (X(2)), and Transcutol P (X(3)). Droplet size (Y(1)), turbidity (Y(2)), and dissolution percentage of GN after 5 (Y(3)) and 30 (Y(4)) min were the dependent variables. A mathematical relationship, Y(3) = -89.3447 + 5.9524X(1) + 1.0683X(2) + 0.462X(3) - 0.0825X(1)(2) -0.0075X(2)(2) -0.0009X(3)(2) + 0.0104X(1)X(2) -0.0113X(1)X(3) + 0.0009X(2)X(3) (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 (Y(3)). The optimized formulation was predicted to dissolution 93.34% of GN at 5 min, when X(1), X(2) and X(3) 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 Y(3) 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.

• 出版日期2009-12
• 单位复旦大学