Formulation optimization of scutellarin-loaded HP-β-CD/chitosan nanoparticles using response surface methodology with Box–Behnken design

The aim of this paper is to investigate and optimize the preparation of scutellarin(SCU)-loaded HP-β-CD/chitosan(CS) nanoparticles(CD/CS-SCU-NPs). CD/CS-SCU-NPs were prepared by ionic cross-linking method and the process and formulation variables were optimized using response surface methodology(RSM) with a three-level, three factor Box–Behnken design(BBD).The independent variables were the added amounts of CS, sodium tripolyphosphate(TPP)and Pluronic F-68 during the preparation. Dependent variables(responses) were particle size and entrapment efficiency. Mathematical equations and respond surface plots were used to correlate independent and dependent variables.The preparation process and formulation variables were optimized to achieve minimum particle size and maximum entrapment efficiency by calculating the overall desirability value(OD). The optimized NP formulation was characterized for particle size, PDI, zeta potential, entrapment efficiency and in vitro drug release.According to the results, an optimized CD/CS-SCU-NP formulation was prepared. Results for particle size, PDI, zeta potential and entrapment efficiency were found to be around 200 nm,0.5, 25 mV, and 70% respectively. For in vitro study, the release of SCU from the NPs exhibited a biphasic release and was in accordance with Higuchi equation. The optimized preparation was simple with the probability for industrialization. The combination use of RSM, BBD and overall desirability values could provide a promising application for incorporating CD into CS nanoparticles as drug delivery carrier and help develop lab-scale procedures.

Optimization for Microbial Degradation of Dibenzothiophene by Pseudomonas sp. LKY-5 Using Response Surface Methodology

In this research, the degradation of dibenzothiophene(DBT) was investigated by using Pseudomonas sp. LKY-5 isolated from oil contaminated soil. The response surface methodology(RSM) based on the Box-Behnken design(BBD) was applied for evaluating the interactive effects of four independent variables including substrate concentration, temperature, pH and agitation rate on the DBT removal response. A total of 29 experiments for four factors at three levels were conducted in present study. A second-order regression model was then developed, and the analysis of variance(ANOVA) illustrated that the proposed quadratic model could be utilized to navigate the design space. The value of determination coefficient(R2=0.953 4) indicated a satisfactory agreement between the quadratic model and the experimental data. It was found that DBT removal was more significantly affected(P<0.000 1) by substrate concentration compared with other three parameters. An 100% degradation of DBT could be obtained by Pseudomonas sp. LKY-5 at a substrate concentration of 100 mg/L.

Optimization of ionic liquid-based microwave-assisted extraction of polyphenolic content from Peperomia pellucida (L) kunth using response surface methodology

Objective: To optimize the ionic liquid based microwave-assisted extraction (IL-MAE) of polyphenolic content from Peperomia pellucida (L) Kunth. Methods: The IL-MAE factors as experimental design parameters, including microwave power, extraction time, ionic liquid concentration, and liquid–solid ratio had been involved. Response surface methodology and Box–Behnken design were used to obtain predictive model (multivariate quadratic regression equation) and optimization of the extraction process. The response surface was analyzed by using the yields of total polyphenolic content as response value. Results: Based on the obtained results the optimum extraction condition, including microwave power of 30% Watts, extraction time of 18.5 min, the ionic liquid concen-tration of 0.79 mol/L, and the liquid–solid ratio of 10.72 mL/g 1-Buthyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4) as a solvent was selected. The regression model was obtained to predicts the yields from Peperomia pellucida:Y = 30.250 – 1.356X1 + 2.655X2 + 2.252X3 – 0.565X4 + 0.990 X1X3 – 8.172 X1X4 – 3.439 X3X4 – 4.178 X12 – 3.210 X32 – 6.786 X42 – 7.290 X12X3 + 5.575 X1X32 – 4.843 X32X4 with R2 = 0.82519. Scale-up confirmation test was obtained the maximum yields of total polyphenolics content with the amount of 31.1725μg GAE/g. Conclusions: The IL-MAE method produced a higher extraction polyphenolic and performed rapidly, easily and efficiently.

Comparison of Response Surface Methodology and Artificial Neural Network in Predicting the Microwave-Assisted Extraction Procedure to Determine Zinc in Fish Muscles

In this paper, the estimation capacities of the response surface methodology (RSM) and artificial neural network (ANN), in a microwave-assisted extraction method to determine the amount of zinc in fish samples were investigated. The experiments were carried out based on a 3-level, 4-variable Box–Behnken design. The amount of zinc was considered as a function of four independent variables, namely irradiation power, irradiation time, nitric acid concentration, and temperature. The RSM results showed the quadratic polynomial model can be used to describe the relationship between the various factors and the response. Using the ANN analysis, the optimal configuration of the ANN model was found to be 4-10-1. After predicting the model using RSM and ANN, two methodologies were then compared for their predictive capabilities. The results showed that the ANN model is much more accurate in prediction as compared to the RSM.

Response Surface Methodology-Based SERS for Determination of Gymnodimine

Gymnodimine (GYM), a fast-acting marine toxin, is destructive to aquaculture and human health through contaminated shellfish. The current detection methods in GYM have definite drawbacks in operation, such as the demand for delicate instruments and the consumption of time. Therefore, silver colloid was utilized as a surface-enhanced Raman scattering (SERS) desirable substrate for sensitive and rapid detection of GYM in lake and shellfish samples. The theoretical spectrum of GYM is calculated by density functional theory (DFT), and the substrate performance is evaluated by a rhodamine 6 G probe. Under the optimal SERS experimental condition calculated by the response surface methodology, the low limit of detection of 0.105 μM with R2 of 0.9873 and a broad linearity range of 0.1 - 10 μM was achieved for GYM detection. In addition, the substrate was satisfyingly applied to detect gymnodimine in the lake and shellfish matrix samples with LOD as low as 0.148 μM and 0.170 μM, respectively. These results demonstrated a promising SERS platform for detecting marine toxins in seafood for food safety and pharmaceutical research.

Optimizing electrocoagulation process for the treatment of biodiesel wastewater using response surface methodology

The production of biodiesel through a transesterification method produces a large amount of wastewater that contains high levels of chemical oxygen demand （COD） and oil and grease （O＆G）. Currently, flotation is the conventional primary treatment for O＆G removal prior to biological treatments. In this study, electrocoagulation （EC） was adopted to treat the biodiesel wastewater. The effects of initial pH, applied voltage, and reaction time on the EC process for the removal of COD, O＆G, and suspended solids （SS） were investigated using one factor at a time experiment. Furthermore, the Box-Behnken design, an experimental design for response surface methodology （RSM）, was used to create a set of 15 experimental runs needed for optimizing of the operating conditions. Quadratic regression models with estimated coefficients were developed to describe the pollutant removals. The experimental results show that EC could effectively reduce COD, O＆G, and SS by 55.43%, 98.42%, and 96.59%, respectively, at the optimum conditions of pH 6.06, applied voltage 18.2 V, and reaction time 23.5 min. The experimental observations were in reasonable agreement with the modeled values.

基于Box-Behnken设计-响应面法优化酒黄精炮制工艺

目的采用Box-Behnken设计-响应面法(Box-Behnken design-response surface method,BBD-RSM)对黄精炮制工艺进行优化,筛选最佳工艺参数。方法研究于2023年1—5月开展。以黄精外观性状、醇浸出物、多糖含量等为评价指标,基于单因素试验进行响应面综合实验,运用BBD-RSM,探索黄精饮片润制时间、蒸制时间、焖制时间等对其品质的影响,优选炮制工艺参数及炮制设备。结果通过拟合模型,外观性状评分、醇浸出物含量、黄精多糖含量预测值分别为72.31分、64.86%、12.96%,优选黄精最佳酒制工艺为润制时间1.5 h、蒸制时间5.5 h、焖制时间1.0 h;蒸制设备拟选用回转式蒸药机,干燥设备拟选用敞开式烘干箱。结论所优选酒黄精炮制工艺合理、可行,为酒黄精炮制生产工艺及设备选型提供了依据。

Optimization of Rooting Medium for Tissue Culture Seedlings of Dendrobium officinale by Response Surface Methodology

[Objectives] To increase the survival rate of tissue culture seedlings of Dendrobium officinale,and optimize the conditions of rooting medium by the response surface methodology( RSM). [Methods]The effects of 6-BA concentration,NAA concentration,potato amount and the amount of mashed banana on the growth of seedlings were determined by single factor experiment and were analyzed by Box-Behnken design and response surface methodology. [Results]The optimal culture conditions: rooting medium 1/2 MS + 6-BA 0. 24 mg/L + mashed banana 87. 63 g/L + potato 89. 30 g/L + NAA 0. 52 mg/L + sucrose 20. 0 g/L + activated carbon 4. 0 g/L + agar 7. 0 g/L,p H 5. 8,and light intensity 2 000 Lx. [Conclusions]The model established by response surface methodology has a good predictability and could be used to optimize the conditions of tissue culture and rooting medium of D. officinale.

Optimization of Extraction Process and Determination of Total Triterpenoids from Semen Trichosanthis by Response Surface Methodology

[Objectives] To optimize the extraction process and determine the total triterpenoids from Semen Trichosanthis.[Methods]The Box-behnken response surface methodology was applied to optimize the extraction conditions of total triterpenoids in Semen Trichosanthis.And the spectrophotometry was used to determine the content of total triterpenoids in Semen Trichosanthis.[Results] The optimal extraction conditions were solid to liquid ratio of 40∶ 1,ultrasonic time of 20 min,and ultrasonic power of 100 W.Under these conditions,the content of total triterpenoids in Semen Trichosanthis was significantly different among the 10 production areas,among which the No.9 production area(Anhui 1) had the highest total triterpenoids content of 45.71 mg/g,while No.7 production area(Shandong) had the lowest total triterpenoids content of 15.22 mg/g.[Conclusions]The Box-behnken response surface methodology is reliable for the extraction of total triterpenoids in Semen Trichosanthis,and the spectrophotometry is proper for determining the content of total triterpenoids in Semen Trichosanthis.There are large differences in the content of total triterpenoids in Semen Trichosanthis produced in different areas.

基于Box-Behnken响应面法优化方便藜麦粥制备工艺

以复水率、复水时间和感官品质为指标,通过单因素试验优选方便藜麦粥的最佳浸泡温度、料水比和蒸煮时间;利用Box-Behnken响应面法优化其制备工艺,并采用加权法计算综合得分。结果表明,最佳制备工艺为浸泡温度41℃,料水比1∶9,蒸煮时间23 min。经验证试验,其综合得分为96.08,与理论预测值(96.43)的相对偏差为0.35%(<5.0%)。优化的方便藜麦粥制备工艺为其开发应用提供重要支撑。

Removal of Mercury(Hg(Ⅱ)) from Seaweed Extracts by Electrodialysis and Process Optimization Using Response Surface Methodology

In this work,response surface methodology(RSM)was employed to model and optimize electrodialysis process for mercury(Hg(II))removal from seaweed extracts.Box-Behnken design(BBD)was utilized to evaluate the effects and the interaction of influential variables such as operating voltage,influent flow rate,initial concentration of Hg(II)on the removal rate of Hg(II).The developed regression model for removal rate response was validated by analysis of variance,and presented a good agreement of the experimental data with the quadratic equation with high value coefficient of determination value(R2=0.9913,RAdj 2=0.9678).The optimum operating parameters were determined as 7.17V operating voltage,72.54L h−1 influent flow rate and 5.04mgL−1 initial concentration of mercury.Hg(II)removal rate of 76.45%was acquired under the optimum conditions,which showed good agreement with model-predicted(75.81%)result.The results revealed that electrodialysis can be considered as a promising strategy for removal of Hg(II)from seaweed extracts.

Box-Behnken响应面法优选紫斑牡丹中丹皮酚和芍药苷提取工艺

目的优选紫斑牡丹中丹皮酚和芍药苷的提取工艺。方法在单因素试验基础上,以液料比、提取时间和乙醇体积分数为影响因素,以丹皮酚和芍药苷提取率的总权重综合评分为评价指标,采用Box-Behnken响应面法优选最佳提取工艺,并进行验证试验。结果最佳提取工艺为液料比28倍,提取时间150 min,乙醇体积分数52%。此工艺条件下,丹皮酚提取率为0.49%(RSD=1.33%,n=3),芍药苷提取率为5.38%(RSD=1.07%,n=3)。结论该提取工艺稳定、可行,可用于紫斑牡丹中丹皮酚和芍药苷的提取。

Box-Behnken响应面法优化羟基红花黄色素A纳米粒处方工艺及体外释放评价

目的优化羟基红花黄色素A(hydroxysafflor yellow A,HSYA)纳米粒制备工艺,并对其进行体外释放评价。方法以乳酸-羟基乙酸共聚物[poly(lactic-co-glycolicacid),PLGA]为载体,利用改良的复乳法制备HSYA纳米粒,通过Plackett-Burman设计实验联用Box-Behnken响应面法优选最佳制备工艺;利用粒径测定仪、TEM扫描电镜仪、傅里叶红外光谱(FT-IR)仪、X-射线粉末衍射(XRD)仪对纳米粒进行表征;并对其进行4℃储藏稳定性、生理介质中稳定性、冻干保护剂及体外释放率考察。结果优选出纳米粒最佳工艺处方为:pH为6.95,投药量为2.8 mg,载体用量为18.2 mg;在此条件下制备出的纳米粒粒径为(176.4±1.29)nm,多分散系数(Polydiseperse Index,PDI)为(0.152±0.014),Zeta电位为(-17.6±0.46)mV,包封率为(78.5±0.49)%,载药量为(7.3±0.07)%,纳米粒形态圆整,分散性好;在4℃储存环境下、不同生理介质中稳定性良好,最佳冻干保护剂为1%葡萄糖;纳米粒48 h体外释放率为85%。结论该优化方法合理可靠,所得纳米粒稳定性良好,具有一定的缓释作用,体外释放符合一级动力学模型。

Response Surface Methodology as an Approach for Optimization of Vinegar Fermentation Conditions Using Three Different Thermotolerant Acetic Acid Bacteria

This study aimed to investigate optimal fermentation conditions of biological acetic acid fermentation for vinegar production. Optimization was performed on 3 acetic acid bacteria strains namely VMA1, VMA7 and VMAO using Response Surface Methodology (RSM). A Box-Behnken-Design (BBD) was achieved with three different independent process parameters involving: fermentation temperature, original alcohol concentration and original acetic acid concentration and one dependent variable (acetic acid yield). The results showed that the mathematical models describe correctly the relationship between responses and factors (F values of the models (p R2 (coefficient of correlation) respectively 0.96, 0.94, 0.98, and adjusted R2 0.95, 0.92, 0.98). The maximum acidity was obtained respectively at fermentation temperatures, original alcohol concentrations and original acetic acid concentrations ranging from [37.5°C - 45°C], [16% - 20% (v/v)], [1.5% - 2% (w/v)] for VMA1, [40°C - 45°C], [14.5% - 20% (v/v)], [1.7% - 2% (w/v)] for VMA7 and [42°C - 45°C], [17% - 20% (v/v)], [1.5% - 2% (w/v)] for VMAO. The use of these acetic strains in the production of vinegar may seriously lead to a decrease or even an ablation of the costs related to the cooling of bioreactors especially in warm and hot countries, in the context of global warming.

单因素考察结合Box-Behnken响应面法优化脑络欣通颗粒制备工艺及对脑卒中大鼠的影响

目的 完善脑络欣通颗粒的生产制造工艺考察研究,筛选出最佳辅料构成和最佳制备工艺条件,为脑络欣通颗粒的开发和应用提供理论和实验基础。方法 通过对脑络欣通颗粒干燥工艺的研究,考察辅料种类、辅料用量以及进风温度。在单因素实验的基础上研究脑络欣通颗粒最佳药物辅料构成,利用综合评分筛选出最佳的辅料种类、最佳的药辅比及最佳的乙醇浓度,再通过使用Box-Behnken响应面法对制备工艺设计进行优化。根据所得工艺进行制粒,对脑卒中模型大鼠进行脑络欣通颗粒剂灌胃给药,初步观察脑络欣通颗粒对脑卒中大鼠的疗效。结果既得颗粒剂干燥工艺研究考察结果中,辅料种类为糊精,辅料用量为5%,进风温度为145℃。脑络欣通颗粒最佳制备工艺:辅料种类为糊精,药辅比为1∶0.5,乙醇体积分数为95%,在此条件下综合评分值为0.872 946。相比脑卒中模型组大鼠,脑络欣通颗粒剂组神经元细胞数目有明显增加,初步推断颗粒剂对脑卒中大鼠有治疗作用。结论采用响应面法优选脑络欣通颗粒的制备工艺结果可靠,稳定性较高,方法简单可行,颗粒剂药效显著,可为脑络欣通颗粒剂的工业化生产提供依据。

基于AHP-CRITIC权重分析法结合Box-Behnken设计-响应面法优化盐橘核水提取工艺

目的:优化盐橘核水提取工艺。方法:以柠檬苦素、诺米林、黄柏酮的转移率及出膏率为评价指标,利用混合加权法(AHP-CRITIC法)确定权重系数,计算多指标综合评分,并结合Box-Behnken设计-响应面法考察饮片粒度、加水量、提取时间的影响,优选盐橘核水提取工艺。结果:优选提取工艺为饮片粒度过6目筛网,一、二煎加水量分别为12倍、10倍,提取时间分别为1.0 h、0.5 h。结论:优选出的提取工艺稳定可行,可为盐橘核工业化生产提供参考。

Box-Behnken响应面法优化“五味子-吴茱萸”药对的提取工艺及含量测定

目的:优化“五味子-吴茱萸”药对提取工艺并测定其不同配伍的化学成分含量。方法:利用Box-Behnken设计在单因素考察的基础上考察“五味子-吴茱萸”药对的提取工艺,确定最佳提取工艺,并通过高效液相色谱法测定“五味子-吴茱萸”的化学含量,确定药对的最佳比例。结果:“五味子-吴茱萸”药对最优提取工艺为乙醇体积分数70%,料液比1∶15(g/mL),提取时间60 min,提取次数3次。该提取工艺科学可靠。结论:本研究方法简单可行,可为“五味子-吴茱萸”药对的开发利用及相关研究提供参考。

基于Box-Behnken响应面法优化膝痛康β-蜕皮甾酮的提取工艺

目的优化膝痛康方剂中β-蜕皮甾酮的提取工艺。方法采用Box-Behnken响应面法和单因素试验,对提取过程中的浸泡时间、提取次数、提取时间和甲醇倍量等进行优化,通过响应面模型分析与预测,得到最佳的提取工艺条件,并对最优条件进行验证。结果饮片浸泡96 min,提取100 min,反复2次,甲醇倍数为16倍,此时牛膝的提取工艺达到最佳,在此提取工艺下β-蜕皮甾酮的提取量达到最大。结论该提取方法具有设备简单、成本低、提取工艺稳定等特点,此外,该提取工艺具有较好的应用价值,以其为膝痛康的应用提供实验依据。

基于Box-Behnken响应面法优化鹿角蛋白的提取工艺

目的 通过Box-Behnken响应面法优化鹿角蛋白的提取工艺。方法 在单因素考察基础上进行响应面法设计,寻找最佳提取条件。以鹿角中蛋白含量为考察指标,使用考马斯亮蓝染色法测量样品溶液吸光度,再通过回归方程计算出样品溶液的鹿角蛋白含量。结果 最优提取工艺条件为NaOH浓度0.35 mol·L^(-1),液料比6:1,提取时间114 min。结论 经验证通过Box-Behnken响应面法所得到的预测值与测定的实际值偏差均在±1%以内,可以为膝痛康中鹿角蛋白的提取工艺提供参考。

主成分分析结合Box-Behnken响应面法优选旋覆代赭汤中酚酸类及黄酮类成分纯化工艺

目的优选旋覆代赭汤中酚酸类及黄酮类成分分离纯化工艺。方法以洗脱流速、醇洗体积分数和醇洗体积为考察因素,采用Box-Behnken响应面法设计试验,HPD400型大孔树脂分离纯化旋覆代赭汤中酚酸类(6个)、黄酮类(3个)成分,超高效液相色谱(UPLC)法测定洗脱液中各成分的含量,紫外-可见分光光度(UV-Vis)法测定洗脱液中总黄酮质量分数。通过主成分分析结合Box-Behnken响应面法,评价模型,预测最佳纯化工艺并验证。结果最佳纯化工艺为,流速2.6 mL/min,醇洗体积分数53%,醇洗体积为2.4 BV。经验证,最佳纯化工艺下总黄酮质量分数为(69.33±1.66)%,绿原酸、咖啡酸、异槲皮苷、异绿原酸B、异绿原酸A、1,5-二咖啡奎宁酸、异鼠李苷、异绿原酸C、槲皮素含量分别为(2.67±0.04)μg/mg、(15.34±0.27)μg/mg、(12.36±0.17)μg/mg、(16.01±0.22)μg/mg、(18.25±0.22)μg/mg、(96.24±1.44)μg/mg、(6.85±0.07)μg/mg、(22.55±0.35)μg/mg、(5.78±0.07)μg/mg。结论优选的大孔吸附树脂纯化旋覆代赭汤中酚酸、黄酮类成分工艺稳定可行,可为进一步药效学研究提供参考。