Department of Pharmaceutics, Rajiv Academy for Pharmacy, National Highway #2, P.O. Chhattikara, Mathura, Uttar Pradesh, 281001, India.
AAPS PharmSciTech. 2010 Jun;11(2):489-96. doi: 10.1208/s12249-010-9414-z. Epub 2010 Mar 23.
The objective of this study was to develop solid lipid nanoparticles (SLNs) of simvastatin and to optimize it for independent variables (amount of glycerol monostearate, concentration of poloxamer, and volume of isopropyl alcohol) in order to achieve desired particle size with maximum percent entrapment efficiency (% EE) and percent cumulative drug release (% CDR). To achieve our goal, eight formulations (F(1)-F(8)) of SLNs were prepared by solvent injection technique and optimized by 2(3) full-factorial design. The design was validated by extra design checkpoint formulation (F(9)), and the possible interactions between independent variables were studied. The responses of the design were analyzed using Design Expert 7.1.6. (Stat-Ease, Inc, USA), and the analytical tools of software were used to draw Pareto charts and response surface plots. On the basis of software analysis, formulation F(10) with a desirability factor of 0.611 was selected as optimized formulation and was evaluated for the independent parameters. Optimized formulation showed particle size of 258.5 nm, % EE of 75.81%, with of 82.67% CDR after 55 h. The release kinetics of the optimized formulation best fitted the Higuchi model, and the recrystallization index of optimized formulation was found to be 65.51%.
本研究旨在开发辛伐他汀固体脂质纳米粒（SLN），并对其进行优化，以独立变量（甘油单硬脂酸酯的用量、泊洛沙姆浓度和异丙醇体积）为变量，以达到所需的粒径，同时获得最大的包封效率（% EE）和累积药物释放百分比（% CDR）。为了实现这一目标，我们采用溶剂注入技术制备了 8 种辛伐他汀 SLN 制剂（F(1)-F(8)），并通过 2(3)完全析因设计进行了优化。通过额外的设计检查点制剂（F(9)）验证了设计的有效性，并研究了独立变量之间的可能相互作用。使用 Design Expert 7.1.6（Stat-Ease，Inc，美国）对设计的响应进行了分析，并使用软件的分析工具绘制了 Pareto 图和响应面图。基于软件分析，选择具有 0.611 理想因子的制剂 F(10)作为优化制剂，并对其进行了独立参数的评估。优化制剂的粒径为 258.5nm，包封率为 75.81%，82.67%的药物在 55 小时后释放。优化制剂的释放动力学最符合 Higuchi 模型，并且优化制剂的重结晶指数为 65.51%。
