Karami Zahra, Khoshkam Maryam, Hamidi Mehrdad
Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Zanjan, Iran.
Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
Drug Res (Stuttg). 2019 May;69(5):256-264. doi: 10.1055/a-0654-4867. Epub 2018 Aug 7.
A seven-factor Box-Behnken design was used for the optimized development of an olive oil-based nanoemulsion (NE) intended for intravenous drug delivery. The independent variables of olive oil concentration, tween 80 concentration, span 80 concentration, rate of adding of oil in aqueous phase, homogenization speed, homogenization time, and preparation temperature, were used as inputs of the factorial design. The response variables were mean droplet diameter, zeta potential (ZP), and polydispersity index (PDI). A quadratic, linear and 2FI model was established to predict the responses based on the multivariate model developed. The obtained experimental responses were in good agreement with predicted values from expert design, showing residual standard error (RSE) less than 10 %. TEM revealed that the optimized nanoemulsions were almost spherical with mean diameter about 40 nm. The developed formulation showed only about 4.6% of hemolysis and was safe for intravenous delivery. As well, the other in vitro characterization of the optimal nanoemulsion such as viscosity, percent transmittance, physical stability, and solubility study revealed it to be promising as an intravenous drug delivery system.
采用七因素Box-Behnken设计对用于静脉给药的橄榄油基纳米乳剂(NE)进行优化开发。将橄榄油浓度、吐温80浓度、司盘80浓度、油相加入水相的速率、匀化速度、匀化时间和制备温度等自变量用作析因设计的输入。响应变量为平均液滴直径、zeta电位(ZP)和多分散指数(PDI)。基于所开发的多变量模型建立了二次、线性和二阶交互作用模型来预测响应。获得的实验响应与专家设计的预测值高度吻合,残余标准误差(RSE)小于10%。透射电子显微镜(TEM)显示,优化后的纳米乳剂几乎呈球形,平均直径约为40 nm。所开发的制剂溶血率仅约为4.6%,静脉给药安全。此外,最佳纳米乳剂的其他体外特性,如粘度、透光率百分比、物理稳定性和溶解度研究表明,它有望成为一种静脉给药系统。