title: Application of Box-Behnken design in understanding the quality of genistein self-nanoemulsified drug delivery systems and optimizing its formulation.
abstract: 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 - 0.0825X(1)(2) - 0.0075X(2)(2) - 0.0009X(3)(2) + 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Saijie
authors.initials: S
authors.lastname: Zhu
authors.forename: Minghuang
authors.initials: M
authors.lastname: Hong
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Yuanying
authors.initials: Y
authors.lastname: Pei
mesh_terms: D000465:Algorithms; D001682:Biological Availability; D002214:Capsules; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions; D005026:Ethylene Glycols / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry; D019833:Genistein / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005989:Glycerides; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D015233:Models, Statistical; D049329:Nanostructures / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods; D009391:Nephelometry and Turbidimetry; D009821:Oils / Q000737:chemistry; D009930:Organic Chemicals / Q000737:chemistry; D010316:Particle Size; D044367:Phase Transition; D012044:Regression Analysis; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D014280:Triglycerides / Q000737:chemistry
chemical_list: D002214:Capsules; D004655:Emulsions; D005026:Ethylene Glycols; D005989:Glycerides; D009821:Oils; D009930:Organic Chemicals; D013501:Surface-Active Agents; D014280:Triglycerides; C542236:labrafac WL 1349; C440220:Labrasol; C000515:cremophor EL; D005780:Gelatin; C010111:carbitol; D019833:Genistein; D005990:Glycerol