Formulation of Dacarbazine-loaded Cubosomes-Part II: Influence of Process Parameters
Formulation of Dacarbazine-loaded Cubosomes-Part II: Influence of Process Parameters
复制标题
DOI：
10.1208/s12249-009-9296-0
复制
发表时间：
2009-09-01
影响因子：
3.3
通讯作者：
Youan, Bi-Botti C.
中科院分区：
文献类型：
--
作者：
Bei, Di;Marszalek, Jacob;Youan, Bi-Botti C.
本研究的目的是研究均质速度（X(1)）、持续时间（X(2)）和温度（X(3)）等工艺参数（自变量）对负载达卡巴嗪立方体制备过程的综合影响。采用Box-Behnken设计对这三个因素对粒径（Y(1)）和包封效率（Y(2)）两个响应的影响进行合理化分析。对自变量和因变量进行多元回归分析，建立全模型二阶多项式方程。计算F值，确认分析中遗漏不重要的参数或参数之间的相互作用，推导出简化模型多项式方程，预测负载达卡巴嗪立方体的Y(1)和Y(2)。还获得了帕累托图，以显示X (1)， X(2)和X(3)对Y(1)和Y(2)的影响。对于Y(1)，通过检查点分析验证了一个模型能够更准确地预测响应参数。自动获得优化过程和Pareto图，预测独立参数X(1)、X(2)和X(3)的水平（分别为0.889794、0.11886和0.56201）和最小值Y(1)。最佳工艺参数（均质速度为24000 rpm，时间为5.5 min，温度为76℃）可制得尺寸为85.6 nm，包封率为16.7%的立方体体。Box-Behnken设计被证明是制备和优化负载达卡巴嗪的立方体体的有用工具。对于包封效率（Y(2)），还需要进一步的研究来增强结果，并完善这种水溶性药物在立方体体中的包封模型。
The purpose of this study is to investigate the combined influence of process parameters (independent variables) such as homogenization speed (X (1)), duration (X (2)), and temperature (X (3)) during the preparation of dacarbazine-loaded cubosomes. Box-Behnken design was used to rationalize the influence of these three factors on two responses, namely particle size (Y (1)) and encapsulation efficiency (Y (2)). Independent and dependent variables were analyzed with multiple regressions to establish a full-model second-order polynomial equation. F value was calculated to confirm the omission of insignificant parameters or interactions of parameters from the analysis to derive a reduced-model polynomial equation to predict the Y (1) and Y (2) of dacarbazine-loaded cubosomes. Pareto charts were also obtained to show the effects of X (1), X (2), and X (3) on Y (1) and Y (2). For Y (1), there was a model validated for more accurate prediction of response parameter by performing checkpoint analysis. The optimization process and Pareto charts were obtained automatically and they predicted the levels of independent parameters X (1), X (2), and X (3) (0.889794, 0.11886, and 0.56201, respectively) and minimized Y (1). The optimal process parameters (homogenization's speed = similar to 24,000 rpm, duration = 5.5 min, and temperature = 76A degrees C) led to the production of cubosomes with 85.6 nm in size and 16.7% in encapsulation efficiency. The Box-Behnken design proved to be a useful tool in the preparation and optimization of dacarbazine-loaded cubosomes. For encapsulation efficiency (Y (2)), further studies are needed to enhance the result and improve the model for such water-soluble drug encapsulation in cubosomes.