Formulation Optimization of Estradiol Microemulsion Using Response Surface Methodology

The aim of the current study was to find an optimal estradiol-loaded microemulsion with higher permeation rate and shortened lag time (LT) for transdermal application by using a response surface methodology (RSM) and constrained mixture design. Isopropyl myristate (X₁), distilled water (X₂), and ethanol (X₃) were selected as independent variables, whereas the viscosity of microemulsion and permeation parameters including the cumulative amount at 24 h (Q_24h) and LT of estradiol-loaded microemulsion through skin were set as dependent variables. The result showedthat the three independent variables had a remarkable effect (p < 0.05) on the dependent variables. Moreover, the predicted and observed values of these three dependent variables of the optimal microemulsion formulations, which were produced by the RSM optimization technique, were close, demonstrating that RSM was a useful technique for optimizing pharmaceutical formulations. However, the experimental estradiol-loaded microemulsion with higher permeation rate was expected to provide effective therapeutic concentration in a workable administration area. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4383–4389, 2011     

星点设计法优化盐酸伊托必利分散片处方

目的：采用湿法制粒工艺制备盐酸伊托必利分散片。方法：以崩解时间、溶出度和混悬系数为评价指标,对辅料用量进行响应面分析法优化设计。结果与结论：处方最优工艺参数：乳糖占44.78%,微晶纤维素占25.75%,交联聚维酮占5.53%。该工艺下样品的崩解时间、溶出度和混悬系数等各指标参数达到较理想结果,符合分散片的质量要求。     

响应面法优化考马斯亮蓝G-250溶液的配制

试验研究了各组分磷酸、乙醇、考马斯亮蓝G-250在考马斯亮蓝G-250溶液中的作用及其对测定蛋白质浓度灵敏度和准确度的影响,结合全波长扫描光谱法分析了溶液配制过程中的变色机理。在此基础上,以一系列牛血清白蛋白溶液标准浓度和测定值之间的差值平方和的均方(S值)为响应值,采用单因素试验和响应面分析法优化考马斯亮蓝G-250溶液的配制条件。结果表明,乙醇是用来降低水溶液的极性环境,促进考马斯亮蓝G-250的溶解;磷酸是为考马斯亮蓝G-250表面电荷发生变化的促进剂;两者构成了影响变色灵敏度的主要因素,考马斯亮蓝G-250分子在溶液中不同的存在形式使反应体系呈现出从蓝色→绿色→棕红色等颜色变化;响应面优化配制条件为:60 mg/L考马斯亮蓝G-250、50 mL/L 95%乙醇、130 mL/L 85%磷酸时,S值最小值为2.07,即在此配制条件下的牛血清白蛋白测定值与标准值最接近。同时以不同标准蛋白质为试样对所配制的溶液进行准确度和灵敏度试验,结果表明对牛血红蛋白、γ-球蛋白测定准确度和灵敏度较好,对胰蛋白酶、胃蛋白酶灵敏度较差,主要原因是由于蛋白质组成差异所引起的。     

响应面法优化白囊耙齿菌多糖提取条件

采用响应面法优化白囊耙齿菌多糖的提取条件.以提取温度、提取时间、水料比(v/w)为影响因素,在单因素试验的基础上,应用Box-Behnken中心组合方法进行三因素三水平试验,以多糖浸出率为响应值,进行响应面分析.结果自囊耙齿菌多糖提取的最佳工艺条件为:提取温度94.7℃,提取时间3.3h,水料比62:1,白囊耙齿菌多精浸出率预测为16.63%,验证值为16.34%,与预测值的相对误差为1.77%.     

Optimization of mead production using Response Surface Methodology

The main aim of the present work was to optimize mead production using Response Surface Methodology. The effects of temperature (x₁: 20–30 °C) and nutrients concentration (x₂: 60–120 g/hL) on mead quality, concerning the final concentrations of glucose (Y₁), fructose (Y₂), ethanol (Y₃), glycerol (Y₄) and acetic acid (Y₅), were studied. Twelve operational conditions were tested. No delays and moods were observed during fermentations. The second order polynomial models determined produced satisfactory fittings of the experimental data with regard to glucose (R² = 0.646, p = 0.001), ethanol (R² = 0.741, p = 0.049), glycerol (R² = 0.899, p = 0.002), fructose (R² = 0.902, p = 0.033) and acetic acid (R² = 0.913, p = 0.001). The optimum extraction conditions determined in order to maximize the combined responses were 24 °C and a nutrients concentration of 0.88 g/L. The mead produced under these conditions had the following characteristics: ethanol concentration of 10.2%, acetic acid 0.54 g/L, glycerol 7.8 g/L, glucose 1.8 g/L and fructose 2.5 g/L. These values were in agreement with the predicted and were within the safe limit established for acetic acid and the recommended range for glycerol. Furthermore, the residual sugars concentration was also low, decreasing the possibility of occurring undesirable refermentations.     

Sodium Diclofenac Encapsulation: Optimization of Encapsulation Efficiency and Particle Size Using Response Surface Methodology

Pharmaceutical Chemistry Journal - This study was carried out to optimize conditions for diclofenac microencapsulation using response surface methodology (RSM). The paper describes preparation,...     

响应面法优化超声波提取昆仑雪菊总黄酮的工艺研究

目的 优化昆仑雪菊的超声提取工艺。方法 以总黄酮提取量为指标,在单因素试验基础上,通过Box-Behnken响应面法考察乙醇体积分数、料液比、超声时间和温度对总黄酮提取效果的影响。结果 最佳超声提取工艺为乙醇体积分数65%,料液比40 g·mL^-1,超声时间34 min,超声温度62 ℃;总黄酮提取量为207.32 mg·g^-1(RSD=1.45%),与预测值(208.81 mg·g^-1)的偏差较小。结论 优选的提取工艺可行,为昆仑雪菊的开发应用提供实验依据。     

Response Surface Methodology to Investigate the Iontophoretic Delivery of Tacrine Hydrochloride

No HeadingPurpose. The objective of this work was to apply response surface approach to investigate the main and interaction effects of delivery parameters for iontophoretic delivery of tacrine HCl in vitro.Methods. Iontophoresis was used to deliver tacrine HCl across rat skin. Experiments were performed according to Box-Behnken design to evaluate effects of drug concentration (X₁), current density (X₂), and donor buffer molarity (X₃) on cumulative drug delivered in 24 h (Y₁), 6 h (Y₂), iontophoretic flux (Y₃), and post-iontophoretic flux (Y₄).Results. Mathematical model for Y₁ was Y₁ = 0.653 + 0.163 * X₁ + 0.456 * X₂ – 0.156 * X₃ + 0.190 * X₁X₂ + 0.139* X₃X₃. Response surface plot indicated that at low level of X₂ (0.1mA/cm²), X₁ had little effect on Y₁. However, at high level of X₂ (0.5 mA/cm²), Y₁ significantly increased from 0.75 mg/cm² to 1.46 mg/cm² when X₁ increased from 1% to 9%. Regression equations predicted responses for Y₁ to Y₄, for optimal formulation, which were in reasonably good agreement with experimental values.Conclusions. Experimental design methodology revealed an interaction between drug concentration and current density, which would have been difficult to predict from one factor at a time classic experimental approach.     

基于星点设计-效应面法优化盐酸曲美他嗪缓释微丸的制备及评价

目的制备盐酸曲美他嗪缓释微丸,并筛选最优处方。方法以体外释放度为考察指标,采用星点设计优化处方并验证。结果成功制备了盐酸曲美他嗪缓释微丸;得到缓释包衣的最优处方为:Eudragit RS100与Eudragit RL100的比例为8.15,包衣增重10.46%;验证实验证明最优处方工艺的重现性良好。结论采用星点设计-效应面法成功得到盐酸曲美他嗪缓释微丸的处方优化模型,实现了处方优化。     

响应面法优化依托泊苷脂质体制备工艺的研究

目的制备依托泊苷脂质体并考察其药剂学性质。方法采用薄膜水化．高压均质法制备依托泊苷脂质体,以胆固醇与氢化磷脂的摩尔比（A）、脂质体溶液中的磷脂浓度（B）、依托泊苷与氢化磷脂的质量比（C）为考察因素,以包封率（y1）、载药量（y2）、综合指标（y3）为响应值,经Box—Behnken效应面法（respon sesurface methodology,RSM）进行处方优化,得到最优处方,并测定脂质体的粒径。结果经RSM优化后,A、B、C分别为0．49,4．96％,0．15;制得的依托泊苷脂质体实测包封率为82．6％,裁药量为11．4％,平均粒径为132．5nm。结论利用Box．Behnken效应面法优化依托泊苷脂质体处方,能制备符合药剂学要求的脂质体,可供体内实验研究。     

达托霉素发酵培养基的响应面法优化

采用Plackett-Bumaan设计、最陡爬坡试验与响应面设计相结合的方法优化达托霉素发酵培养基组成,利用Design Expert 7.0软件设计试验并分析数据.结果表明,培养基中的糊精、酵母粉、酪蛋白水解物是影响达托霉素产量的主要因素.优化后的培养基组成/g·L~(-1)为:糊精10.6,酵母粉1.6,酪蛋白水解物1.3,硫酸钾8,L-门冬氨酸1.5;pH 6.5.在此条件下,达托霉素产量为37.16 me,/L.进一步优化前体癸酸的添加量,最终达托霉素产量达46.54 mg/L.     

Response Surface Methodology for the Optimization of Celecoxib Self-microemulsifying Drug delivery System

The aim of the present study was to prepare, evaluate and optimize, self micro emulsifying drug delivery system of celecoxib. A 3 factor, 3 level factorial design was used for the optimization procedure with different amounts of Labrafil 2609 WL, Labrasol, and Cremophor EL as the independent variables. The response variable was selected on particle size (nm) of the droplets after dilution in 0.1N HCl. Particle size of the self micro-emulsifying drug delivery system depends on the quantity of above three independent variables. Three different levels of each independent variable were selected for the optimization. Mathematical equation and response surface plots were used to relate the dependent and independent variables. The regression equation generated for the particle size after dilution was, Particle size (Y)= +27.83+76.07×A-23.62×B-43.83×C+52.72×A(2)+9.82×B(2)+27.20×C(2)-14.52×A×B-32.38×A×C+12.1×B×C, where, A=Labrafil 2609 WL, B= Labrasol, C= Cremophor EL, Y= particle size. The optimized model predicted a particle size of 28.33 nm with 0.16ml of labrafil 2609 WL, 0.17ml Labrasol and 0.22ml of Cremophor EL. The observed response were in close agreement with the predicted values of the optimized formulation. This demonstrates the reliability of the optimization procedure in predicting particle size of self microemulsifying delivery system for celecoxib.     

响应面法优化罗麦颗粒成型工艺的研究

摘 要 目的：优化罗麦颗粒剂的最佳成型工艺。方法: 以合格颗粒收率及吸湿性为指标对赋形剂的种类进行筛选,通过对制粒效果的考察,优选赋形剂的最佳混合比例。以合格颗粒收率、溶化性、吸湿性、感官评价的总评“归一值”作为评价指标,选取辅料倍数、乙醇浓度、柠檬酸用量为主要影响因素,采用3因素5水平中心组合设计—响应面法优化罗麦颗粒成型工艺。结果: 确定了糖粉和麦芽糊精为颗粒的赋形剂,且糖粉和麦芽糊精的最佳混合比例为3∶1。罗麦颗粒的最佳成型工艺是赋形剂用量为提取物的5倍量,润湿剂为85%乙醇,柠檬酸含量为0.3%。结论:运用中心组合设计—响应面法制备所得的罗麦颗粒具有合格收率高、吸湿性小、溶化性好、口感柔和且服用量适中等优点,表明优化罗麦颗粒湿法制粒的工艺合理、可行。     

响应面法优化富马酸喹硫平缓释片处方

目的:优化富马酸喹硫平缓释片处方。方法:以累积释放度综合评分作为响应值,采用3因素3水平的响应面法,确定富马酸喹硫平缓释片处方中羟丙甲纤维素(HPMC)的黏度、用量与枸橼酸钠、乳糖的用量,并探讨其体外释药机制。结果:骨架材料选择HPMC K15M,考虑到实际操作便利确定其用量为13.5%,枸橼酸钠用量为9.5%,乳糖用量为14%。缓释片体外释放符合Higuchi方程,释药机制为扩散和溶蚀并存的双重机制。结论:筛选所得的富马酸喹硫平缓释片处方工艺稳定可行,有一定的缓释作用。     

响应面优化香菇多糖超声波辅助热水浸提工艺

目的研究香菇多糖超声波辅助热水浸提的最佳工艺。方法采用响应面优化法对香菇多糖超声波辅助热水浸提工艺进行条件优化,以料液比、超声功率、超声时间和超声温度为影响因素,在单因素实验的基础上,应用Box-Behnken中心组合实验方案进行四因素三水平实验设计,以多糖得率为响应值进行响应面分析。结果最佳工艺为：料液比为1：34．6,超声功率为97W,超声时间为41．3min,超声温度为81．2℃,在此条件下多糖得率为8．49％。结论此工艺合理可行,适用于香菇多糖的提取。     

响应面法优化连翘苷超声提取工艺

在单因素实验基础上,采用Box-Behnken中心组合设计原理优化提取溶剂甲醇的浓度、超声提取时间、超声功率和液料比.以连翘苷得率为响应值进行多元二次响应回归分析,得到连翘苷的最佳提取工艺条件为:甲醇浓度100%,超声提取时间27min,超声功率416 W,液料比12:1.回归模型预测最优条件下连翘苷得率为0.082%,验证值为0.080%,与预测值的相对误差为2.39%.     

应用Box-Behnken效应面法优化替硝唑胃漂浮片处方

目的:应用Box-Behnken效应面法优化替硝唑胃漂浮片处方。方法:采用Box-Behnken设计试验,考察羟丙基甲基纤维素(HPMC)、卡波姆及海藻酸钠三者在处方中的用量对缓释片的漂浮性能和释药性能的影响,通过二项式方程拟合因素与响应值之间的数学关系以优化处方,对体外释药数据进行方程拟合,探讨其释药机制。结果:优化处方为HPMC30%、卡波姆14%、海藻酸钠18%,优化处方的实测值与预测值之间比较接近;药物的释放模型符合Higuchi方程(r=0.9879),释药机制为骨架溶蚀与药物扩散双重作用。结论:通过Box-Behnken效应面法建立的模型可用于替硝唑胃漂浮片处方的优化。     

响应面法优化巴戟天低聚糖提取工艺

目的:优化巴戟天低聚糖提取工艺。方法:以液料比、提取时间和提取温度为考察因素,以巴戟天低聚糖提取率为评价指标,在单因素试验的基础上,采用3因素3水平Box-behnken中心组合试验,建立低聚糖提取得率的二次多项式回归方程,经响应面回归分析得到优化组合条件并进行验证。结果:最优提取工艺条件为液料比23∶1(ml/g)、提取时间1.7 h、提取温度93℃、提取2次。该条件下3次验证试验低聚糖提取率实测均值为10.29%(RSD=0.20%,n=3),与预测值10.37%相比偏差为0.06%。结论:采用响应面法可实现巴戟天低聚糖提取工艺的优化。