Optimization of Extraction Process of Clerodendrum philippinum Schauer var. simplex Mlodenke Total Flavonoids(CPTF) by Central Composite Design-Response Surface Methodology

[Objectives] The research aimed to optimize extraction process of Clerodendrum philippinum Schauer var. simplex Mlodenke total flavonoids( CPTF),and provide reference for its development and utilization. [Methods] Based on single-factor test,ethanol concentration,extraction temperature and extraction time were taken as independent variables,and total flavonoids yield was taken as dependent variable. The test was conducted according to central composite design principle. Multivariate linear regression and binomial equation fitting of the result were conducted,and extraction process of CPTF was optimized by using response surface methodology. [Results]The optimal extraction process of CPTF was as below: ethanol concentration 54. 76%,extraction temperature 83. 92℃,extraction time 102. 64 min,solid-liquid ratio 1:20,extraction for twice. [Conclusions] The extraction process of CPTF by central composite design-response surface methodology was simple and feasible,with reliable prediction result,which was suitable for industrial production.

Optimization of Extraction Process of Total Flavonoids from Akebia trifoliata (Thunb.) Koidz. by Central Composite Design-Response Surface Methodology

[Objectives]To optimize extraction process of total flavonoids from Akebia trifoliata( Thunb.) Koidz.,so as to provide references for development and use of Akebia trifoliata( Thunb.) Koidz. [Methods]The extraction rate of total flavonoids of Akebia trifoliata( Thunb.)Koidz. was taken as observation indicator. On the basis of single factor experiment,central composite design( CCD) was used to evaluate the effects of the extraction temperature,extraction time,and ethanol concentration on the extraction process. Multiple linear regression and binomial fitting were used,and response surface methodology( RSM) was used to select the optimum extraction process. [Results] The optimum extraction process conditions for total flavonoids of Akebia trifoliata( Thunb.) Koidz. was extraction temperature: 83. 92 ℃; extraction time:96. 47 min; ethanol concentration: 63. 92%; extraction times: two times; solid to liquid ratio: 1 ∶ 20; extraction rate of total flavonoids:4. 55%. [Conclusions] The central composite design-response surface methodology( CCD-RSM) is simple,convenient,and feasible for extraction of total flavonoids from Akebia trifoliata( Thunb.) Koidz.,and the prediction results are reliable.

Extraction Process Optimization of Total Flavonoids from Mallotus apelta Stems by Central Composite Design/Response Surface Method

[Objectives] To optimize the extraction process of total flavonoids in stems of Mallotus apelta. [Methods]On the basis of singlefactor test,with volume fraction of ethanol,extraction time and ratio of solvent as independent variables,the content of total flavonoids as dependent variables,the completely secondary response surface regression fitting was conducted on the independent and dependent variables,and the Response Surface Method was used to optimize the optimum extraction process of total flavonoids in Mallotus apelta stems and predict the optimum process. [Results] The optimum extraction process of total flavonoids in Mallotus apelta was determined as follows: ethanol concentration of 71. 5%; extraction time of 154. 6 min; solid-liquid ratio of 1∶19. 2; total flavonoids content of 7. 060 mg/g; fitted binomial squared correlation coefficient R^2= 0. 8751.[Conclusions]Composite Design/Response Surface Method could be used in the extraction process optimization of total flavonoids in Mallotus apelta stems,the mathematical model established had high prediction accuracy,the method was simple and operability was good.

Optimization and characterization of nimesulide bilayer tablets by response surface methodology

The objectives of this present investigation were to develop and formulate nimesulide bilayer tablets by using different polymer combinations and fillers, to optimize the formulations for different drug release variables by orthogonal design and central composite design-surface methodology and to evaluate drug release pattern of the optimized product. The bilayer tablet containing a fast release layer（FRL） and a sustained release layer（SRL） provided an initial burst release of nimesulide, followed by the sustained release for a period of time. The optimal formulation obtained was as follows：（I） the formulation of FRL： nimesulide, 50 mg; lactose, 92 mg; starch, 22 mg; CCMC-Na, 14 mg; PVP K30, 1 mg; micronized silica gel, 1 mg; magnesium stearate, 0.9 mg; and iron oxide red, 0.1 mg; and（II） the formulation of SRL： nimesulide, 150 mg; HPMC K100LV, 26 mg; HPMC K4M, 33 mg; lactose, 54 mg; PVP K30, 1 mg; micronized silica gel, 1 mg; and magnesium stearate, 0.9 mg. According to the optimal formulation, the biphasic type of release was identified. The in vitro drug dissolution from the bilayer tablets was sustained for about 16 h after releasing 15% of drug in the first 10 min. The developed nimesulide bilayer tablets with improved efficacy can perform therapeutically better than the conventional tablets.

Optimization for supercritical CO_2 extraction of icariin by response surface method

The aim of the present study was to optimize the supercritical CO_2 extraction conditions of icariin from Herba Epimedii by response surface method(RSM) and central composite design(CCD).A 3-factor,5-level CCD was used for the optimization.Independent variables were extraction temperature,extraction pressure and entrainer flow rate.Dependent variable was yield ratio of icariin from Herba Epimedii.A two-order polynomial equation was fitted to the data.The results showed that the optimum extraction conditions were as follows:extraction temperature 46.5℃,extraction pressure 30.6 MPa,entrainer flow rate 3.3 mL/min.CCD/ RSM is convenient and highly predictive for optimizing the extraction process of icariin from Herba Epimedii.

硼砂煅制工艺优化及质量评价

目的 优化硼砂煅制工艺,并对其进行质量评价。方法 以铺设厚度、煅制温度、煅制时间为影响因素,失水率、蓬松度、粉碎率、四硼酸钠含量为评价指标,星点设计-效应面法优化硼砂煅制工艺。采用扫描电镜(SEM)、热重分析(TG)、拉曼光谱、X射线衍射(XRD),比较硼砂煅制前后质量差异。结果 最佳条件为铺设厚度2 cm,煅制温度365℃,煅制时间100 min。煅制后,硼砂微观形态、成分组成、晶型结构发生变化,失去全部结晶水而转变为非晶体状态。结论 该方法稳定可行,可用于工业大批量生产煅硼砂。

基于星点设计-效应面法联用正交设计优选抗骨质疏松颗粒的制剂工艺

目的用星点设计-效应面法(CCD-RSM)联用正交实验设计优选抗骨质疏松颗粒的制剂工艺。方法以溶媒用量、煎煮时间为考察因素,以有效成分补骨脂素、异补骨脂素总量和干膏收率的总评“归一值”(optical density,OD)为评价指标,用CCDRSM确定最佳提取工艺;以颗粒溶化性、吸湿率、水分、成型率、休止角为评价指标,用正交实验优选最佳成型工艺。结果最佳提取工艺为加水量12倍,提取2次,每次130 min;成型工艺为浸膏与辅料的比例为1∶2,可溶性淀粉与糊精的比例为1∶3,用体积分数为90%的乙醇制粒,75℃干燥,过16目筛整粒,即得。结论优选的制剂工艺条件稳定、可行,可为抗骨质疏松颗粒的实际生产提供依据。

层次分析-熵权法联合星点设计-响应面法优选胆汁制陈皮炮制工艺及饮片色度与成分相关性分析

目的研究胆汁制陈皮炮制的最佳工艺参数,明确饮片色度与主要成分之间的关系。方法采用星点设计-响应面法,以辅料用量、蒸制时间、干燥时间、干燥温度为考察因素,以橙皮苷、川陈皮素、橘皮素、牛磺胆酸钠含量及外观性状、醇浸出物含量为评价指标,采用层次分析-熵权法对各评价指标赋予相应权重,计算总评归一值,优选最佳炮制工艺;采用相关性分析和回归分析研究饮片色度与主要有效成分含量的相关性,构建色度-成分的回归方程。结果胆汁制陈皮最佳炮制工艺为每100g陈皮用20g蛇胆汁浸渍完全后,蒸制15min,45℃干燥162min。饮片色度值L^(*)、b^(*)值与橙皮苷、川陈皮素、橘皮素、牛磺胆酸钠4种成分含量均具有显著相关性,a^(*)值仅与牛磺胆酸钠含量具有相关性;构建了L^(*)、b^(*)值与4种成分含量及a^(*)值与牛磺胆酸钠含量的线性回归方程。结论采用星点设计-响应面法优化的胆汁制陈皮炮制工艺具有合理性、可行性,饮片色度与成分含量具有显著相关性。

黑豆与黄酒共制女贞子炮制工艺优化

目的优化黑豆与黄酒共制女贞子炮制工艺。方法在单因素试验基础上,以蒸制时间、蒸制次数、烘制温度为影响因素,外观性状,红景天苷、特女贞苷、女贞苷G13、醇溶性浸出物含量,DPPH、ABTS自由基清除率的总评“归一值”(OD值)为评价指标,星点设计-响应面法优化炮制工艺。结果最优工艺为蒸制时间70 min,蒸制次数7次,烘制温度90℃,OD值为0.8415。结论该方法简便可靠,稳定可行,可用于黑豆黄酒共制女贞子。

基于响应面法中BBD法和CCD法的丙烷回收参数优化对比

为优化丙烷回收工艺运行参数,以丙烷回收率和单位综合能耗为响应值,采用响应曲面法中的Box-Behnken设计(BBD)和中心复合设计(central composite design,CCD)试验优化工艺参数,从方差分析、帕累托图分析、响应面分析和优化结果4个方面优选最佳试验方法。结果显示,CCD法建立的二次响应回归模型的显著性优于BBD法,且CCD法响应曲面分析参数交互作用的显著性结果与方差分析一致。CCD法优化得到的最佳工艺如下:脱乙烷塔压力为3250 kPa,低温分离器温度为-55.6℃,液相回流比为98%,丙烷回收率为98.1%,单位综合能耗为114.1 kgce/10^(4)m^(3)(1 kgce=29.3076 MJ)。在最优工艺参数条件下,丙烷回收率增加了4.36%,产品收益达到3.548万元/d,且预测误差均小于0.2%。

复方产乳灵颗粒成型工艺优化及其吸湿性研究

目的优化复方产乳灵颗粒成型工艺,并考察其吸湿性。方法以辅料(淀粉与糊精)与浸膏粉比例、辅料比例、润湿剂(乙醇)体积分数为影响因素,颗粒合格收率、溶化时间、吸湿率的总评“归一值”(OD值)为评价指标,星点设计-响应面法优化成型工艺。再建立吸湿率动力学模型,测定临界相对湿度。结果最佳条件为辅料与浸膏粉比例0.8∶1,辅料比例0.8∶1,润湿剂体积分数72.0%,OD值为0.62。吸湿动力学模型满足指数模型,临界相对湿度为63.7%。结论该方法简便可行,可为复方产乳灵颗粒的生产和储存提供依据。

骨痛消涂膜剂制备工艺优化及其质量评价

目的优化骨痛消涂膜剂制备工艺,并进行质量评价。方法在单因素试验基础上,以甘油、聚丙烯酸树酯、三乙酸甘油酯、吐温-80用量为影响因素,成膜时间、成膜性、柔韧性、均匀度、黏稠度、表面有无气泡的综合评分为评价指标,星点设计-效应面法优化制备工艺。HPLC法测定雪上一枝蒿甲素含量。结果最佳条件为聚丙烯酸树脂用量41.86%,三乙酸甘油酯用量2.99%,甘油用量5.78%,吐温-80用量2.96%,综合评分为8.93分。雪上一枝蒿甲素在0.017~0.544 mg/mL范围内线性关系良好(r=0.9997),3个水平平均加样回收率分别为99.05%、98.81%、98.92%,RSD分别为0.80%、0.45%、1.07%。结论该方法简便准确,重复性好,可用于骨痛消涂膜剂的制备和质量控制。

复方石斛黄精颗粒剂成型工艺研究

目的:优化复方石斛黄精颗粒剂提取及成型工艺。方法:以多糖提取率为指标,优化复方石斛黄精颗粒提取工艺,以颗粒成型率、休止角、吸湿性和溶化性为指标,研究最优成型工艺。结果:复方石斛黄精颗粒最佳提取工艺为料液比为1∶23(g/mL)、提取温度为76.8℃、提取时间为132.3 min。最佳成型工艺为乳糖与糊精的比例为2.38∶1;赋形剂与浸膏的比例为3.36∶1。结论:优选的提取及成型工艺稳定可靠,为复方石斛黄精颗粒剂实现工业生产提供理论依据。

星点设计-效应面法优化仑伐替尼混合胶束的制备工艺

目的优化仑伐替尼混合胶束的处方及其制备工艺。方法以Pluronic P123和F127作为载体材料,通过薄膜水化法制备仑伐替尼混合胶束。利用单因素实验和星点设计-效应面法筛选出最优处方并对其物理性质进行初步表征。结果优化后的最佳处方和工艺条件为:P123质量百分比80%、载体材料用量90 mg、投药量10 mg、水化体积6 ml、水化时间45 min、旋蒸温度55℃。制备得到的仑伐替尼混合胶束的平均粒径为(104.0±0.32)nm,PDI为0.22±1.19,Zeta电位为(-2.56±0.81)mV,平均包封率为83.33%±0.30%,平均载药量为8.67%±0.07%。胶束形态为分布均一的规整球形,并显示出一定的缓释性能。结论该研究开发的制备工艺简单可行,所得载药胶束具有较高的载药量和包封率且释放稳定,为仑伐替尼混合胶束的进一步研究和开发提供了有价值的参考。

RSM优化焚烧底灰胶凝材料及安全性评价

为了将生活垃圾焚烧底灰(MSWI-BA)进行资源化利用,基于响应面中心复合试验法(RSM-CCD)研究了不同活性激发方式对经过预处理的MSWI-BA水泥胶砂试块28 d抗压强度的影响.结果表明:活性激发MSWI-BA胶凝材料具有较好的胶凝活性;采用RSM-CCD得到,掺10%MSWI-BA水泥胶砂试块在最佳试验条件下的28 d抗压强度计算值为46.04 MPa,实测值为46.15 MPa,二者符合较好,为MSWI-BA的资源化利用提供了一种解决方法;MSWI-BA胶凝材料的安全性较好,重金属浸出性能满足GB 30760—2014《水泥窑协同处置固体废物技术规范》的要求.

血根碱壳聚糖微球的制备工艺优化及体内外性能研究

本研究旨在探讨血根碱壳聚糖微球的最优制备方法,并对微球进行外观粒径表征和体内外研究。本研究建立了血根碱含量测定的HPLC法,运用乳化交联法制备血根碱壳聚糖微球,以载药量、包封率和平均粒径为评价指标,应用单因素试验和星点设计-响应面法优化制备处方。利用显微镜和扫描电镜观察微球外观形态,通过激光粒度仪测定微球粒径及其分布。采用动态透析法取不同时间点的血根碱原料药溶液和血根碱壳聚糖微球溶液,并考察两种溶液的体外释放度,最后进行药动学方程拟合。对不同组小鼠注射血根碱原料液和血根碱微球液,不同时间取组织血测定,观察体内分布及靶向性。结果表明:血根碱HPLC含量测定得曲线方程y=2.530 0x+43.323 1(R^(2)=0.999 8,线性范围为10.0~50.0μg/mL)。单因素试验和星点设计-响应面法得最优处方:血根碱投药量60 mg,壳聚糖用量70mg,乳化剂用量5%,戊二醇用量0.25mL、水油体积比3:10,醋酸浓度2%、搅拌速度500r/min和交联时间3.5h。观察到血根碱壳聚糖微球形态近似球形及表面较光滑,测定得平均粒径(8.17±0.16)μm,粒径分布为2~20μm。体外释放显示,血根碱壳聚糖微球较血根碱原料药释放缓慢,Ritger-Peppas方程拟合效果较好(R^(2)=0.980 8)。血根碱微球在小鼠体内有明显缓释作用,在肺部和肝脏存在不同程度靶向性。血根碱壳聚糖微球体外释放具有明显的缓释作用,在小鼠体内分布具有一定靶向性和缓释性。

Optimization for supercritical CO2 extraction of icariin by response surface method

The aim of the present study was to optimize the supercritical CO2 extraction conditions of icariin from Herba Epimedii by response surface method （RSM） and central composite design （CCD）. A 3-factor, 5-level CCD was used for the optimization. Independent variables were extraction temperature, extraction pressure and entrainer flow rate. Dependent variable was yield ratio of icariin from Herba Epimedii. A two-order polynomial equation was fitted to the data. The results showed that the optimum extraction conditions were as follows： extraction temperature 46.5 ℃, extraction pressure 30.6 MPa, entrainer flow rate 3.3 mL/min. CCD/RSM is convenient and highly predictive for optimizing the extraction process of icariin from Herba Epimedii.

Optimization of fermentation process of papaya sauerkraut using response surface method

Papaya,a tropical fruit was used as the raw material to produce sauerkraut in the study.Three lactic acid bacteria strains isolated from papaya were added to the sauerkraut to facilitate the fermentation of papaya sauerkraut.In the fermentation process,the dynamic changes of total acid in sauerkrauts at different levels of sugar concentration,salt concentration,inoculation and temperature were studied.The response surface method was used to study the effects of changes in multiple factors at the same time.On the basis of“one-variable-at-a-time”approach,the response surface method optimized papaya sauerkraut fermentation process.According to the change of total acid in single factor,29 experiments were designed by 4×3 factorial central composite design.The optimum fermentation conditions were obtained as follows:sugar at 3.8%,salt at 2.8%,inoculation at 5%,and temperature at 31℃.

水飞蓟素磷脂复合物的制备及体外溶出行为评价

目的将水飞蓟素和磷脂复合以研制水飞蓟素磷脂复合物(silymarin phospholipids complex,SM-PC),并考察其基本理化性质。方法采用溶剂挥发法制备SM-PC。通过前期的单因素考察,选择脂药比、药物浓度以及反应温度作为星点设计-效应面法的考察因素,以SM-PC的复合率为衡量指标筛选最佳研制工艺,并测定SM-PC的体外溶出度。结果SM-PC的最优制备条件如下:以丙酮为反应溶剂,水飞蓟素与大豆卵磷脂的比例为1∶1.8,反应温度56℃,反应物的浓度8.0 mg/ml。在此条件下制备3批样品得到SM-PC的复合率为(95.15±1.55)%,偏差<3%。体外溶出试验表明,SM-PC各组分在60 min的溶出接近90%,主要成分水飞蓟宾的溶出行为与市售水飞蓟素胶囊相似,远高于原料药。结论采用星点设计-效应面法成功制备SM-PC,明显提高了溶出度,为后续制剂的研究奠定基础。

茶树油微乳的制备及体外评价研究

目的:采用星点设计-效应面法优化茶树油微乳的配方与制备,并对最优配方进行体外评价研究。方法:通过伪三元相图筛选茶树油微乳的配方组成;固定油相质量分数,采用星点设计-效应面法以混合乳化剂的质量分数和乳化剂与助乳化剂的比例为考察因素,微乳粒径、Zeta电位及多分散系数PI为效应值,采用Design-Expert8.05b软件筛选并验证最优配方,将优化配方进行体外评价试验。结果:茶树油微乳最佳配方为:油相(茶树油)质量分数为5%,乳化剂(Kolliphor RH40)质量分数为11.12%,助乳化剂(Trabscutol P)质量分数为15.44%,水质量分数为68.44%;其平均粒径为17.53 nm, Zeta电位为-16.36 mv, PI为0.035;茶树油微乳体外12 h累积透皮量是茶树油稀释液的3倍,稳定性良好。结论:星点设计-效应面法所建立的模型预测性良好,能方便准确地得到茶树油微乳的较优配方,可为茶树油临床制剂的研发提供参考。