Preparation and characterization of a novel pH-sensitive chitosan-g-poly (acrylic acid)/attapulgite/sodium alginate composite hydrogel bead for controlled release of diclofenac sodium

A series of pH-sensitive composite hydrogel beads composed of chitosan-g-poly (acrylic acid)/attapulgite/sodium alginate (CTS-g-PAA/APT/SA) was prepared as drug delivery matrices crosslinked by Ca²⁺ owing to the ionic gelation of SA. The structure and surface morphology of the composite hydrogel beads were characterized by FTIR and SEM, respectively. pH-sensitivity of these composite hydrogels beads and the release behaviors of drug from them were investigated. The results showed that the composite hydrogel beads had good pH-sensitivity. The cumulative release ratios of diclofenac sodium (DS) from the composite hydrogel beads were 3.76% in pH 2.1 solution and 100% in pH 6.8 solutions within 24 h, respectively. However, the cumulative release ratio of DS in pH 7.4 solution reached 100% within 2 h. The DS cumulative release ratio reduced with increasing APT content from 0 to 50 wt%. The drug release was swelling-controlled at pH 6.8.     

Formulation optimization of chelerythrine loaded O-carboxymethylchitosan microspheres using response surface methodology

The aims of this investigation were to develop a procedure to prepare chelerythrine (CHE) loaded O-carboxymethylchitosan (O-CMCS) microspheres by emulsion cross-linking method and optimize the process and formulation variables using response surface methodology (RSM) with a three-level, three-factor Box-Behnken design (BBD). The independent variables studied were O-CMCS/CHE ratio, O/W phase ratio, and O-CMCS concentration, dependent variables (responses) were drug loading content and encapsulation efficiency. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The process and formulation variables were optimized to achieve maximum drug loading content and entrapment efficiency by the desirability function. The optimized microsphere formulation was characterized for particle size, shape, morphology and in vitro drug release. Results for mean particle size, drug loading content, entrapment efficiency, and in vitro drug release of CHE-loaded O-CMCS microspheres were found to be of 12.18 μm, 4.16 ± 3.36%, 57.40 ± 2.30%, and 54.5% at pH 7.4 after 70 h, respectively. The combination use of RSM, BBD and desirability function could provide a promising application for O-CMCS as controlled drug delivery carrier and help to develop procedures for a lab-scale microemulsion process.     

Optimization of calcium pectinate gel beads for sustained-release of catechin using response surface methodology

Response surface methodology was used to optimize bead preparation conditions, including CaCl₂ concentration (X₁), hydroxypropylmethylcellulose concentration (X₂), and bead-hardening time (X₃), for the sustained-release of catechin from the calcium pectinate gel beads reinforced with liposomes and hydroxypropylmethylcellulose into simulated gastric fluid (SGF) and intestinal fluid (SIF). The optimized values of X₁, X₂, and X₃ were found to be 5.82%, 0.08%, and 10.29 min, respectively. The beads prepared according to the optimized conditions released only about half of the entrapped catechin into SGF while most of the entrapped catechin was released into SIF after 24 h incubation.     

Isolation and characterization of Aspergillus sp. for the production of extracellular polysaccharides by response surface methodology

In this study, Aspergillus sp. was isolated for the production of extracellular polysaccharide. The process parameters were initially optimized by traditional methods. The cheap substrate, wheat bran was used for the production of extracellular polysaccharide in solid state fermentation. Supplementation of (1%, w/w) maltose, gelatin enhanced EPS production (5.36?mg/g). The salts such as, Cu²⁺ (4.9?mg/g), Ca²⁺ (3.5?mg/g), Zn²⁺ (2.9?mg/g), Mn²⁺ (3.4?mg/g) and Mg²⁺ (1.8?mg/g) stimulated EPS production. In two level full factorial experimental designs, the EPS yield varied from 3.18 to 11.65?mg/g wheat bran substrate with various combinations of the components supplemented with wheat bran substrate. Among these selected factors in central composite design, maltose significantly influenced on extracellular polysaccharide production.     

Application of reverse micelle extraction process for amylase recovery using response surface methodology

The effect of different process variables of reverse micelle extraction process like pH, addition of surfactant (AOT) concentration and potassium chloride (KCl) concentration on amylase recovery has been studied and analysed. Solid-state fermentation was used for the production of amylase enzyme. Response surface methodology (RSM) using central composite rotatable design (CCRD) was employed to analyse and optimize the enzyme extraction process. The regression analysis indicates that the effect of AOT concentration, and KCl concentration were significant, whereas the effect of pH was non-significant on enzyme recovery. For the maximum recovery of enzyme, the optimum operating condition for pH, AOT concentration (M) and KCl concentration were 10.43, 0.05 and 1.00, respectively. Under these optimal conditions, the enzyme recovery was 83.16%.     

Response surface methodology for the optimization of ubiquinone self-nanoemulsified drug delivery system

The aim of the present study was to prepare and evaluate an optimized, self-nanoemulsified drug delivery system of ubiquinone. A 3-factor, 3-level Box-Behnken design was used for the optimization procedure with the amounts of Polyoxyl 35 castor oil (X₁), medium-chain mono- and diglyceride (X₂), and lemon oil (X₃) as the independent variables. The response variable was the cumulative percentage of ubiquinone emulsified in 10 minutes. Different ubiquinone release rates were obtained. The amount released ranged from 11% to 102.3%. Turbidity profile revealed 3 regions that were used to describe the progress of emulsion formation: lag phase, pseudolinear phase, and plateau turbidity. An increase in the amount of surfactant decreased turbidity values and caused a delay in lag time. Addition of cosurfactant enhanced the release rates. Increasing the amount of the eutectic agent was necessary to overcome drug precipitation especially at higher loading of surfactants and cosurfactants. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equation generated for the cumulative percentage emulsified in 10 minutes was Y1=90.9–22.1X₁+5.03X₂+13.95X₃+12.13X₁X₂+15.13X₁X₃-14.40X₁ ²-6.25X₃ ². The optimization model predicted a 93.4% release with X₁, X₂, and X₃ levels of 35, 35, and 30 respectively. The observed responses were in close agreement with the predicted values of the optimized formulation. This demonstrated the reliability of the optimization procedure in predicting the dissolution behavior of a self-emulsified drug delivery system. Published: February 8, 2002.     

Optimization of culture conditions for production of cis-epoxysuccinic acid hydrolase using response surface methodology

Response surface methodology, which allows for rapid identification of important factors and optimization of them to enhance enzyme production, was employed here to optimize culture conditions for the production of cis-epoxysuccinic acid hydrolase from Bordetella sp. strain 1–3. In the first step, a Plackett–Burman design was used to evaluate the effects of nine variables (yeast extract, cis-epoxysuccinic acid, KH₂PO₄, K₂HPO₄ · 3H₂O, MgSO₄ · 7H₂O, trace minerals solution, culture volume, initial pH and incubation time) on the enzyme production. Yeast extract, cis-epoxysuccinic acid and KH₂PO₄ had significant influences on cis-epoxysuccinic acid hydrolase production and their concentrations were further optimized using central composite design and response surface analysis. A combination of adjusting the concentration of yeast extract to 7.8 g/l, cis-epoxysuccinic acid to 9.8 g/l, and KH₂PO₄ to 1.12 g/l would favor maximum cis-epoxysuccinic acid hydrolase production. An enhancement of cis-epoxysuccinic acid hydrolase production from 5.6 U/ml to 9.27 U/ml was gained after optimization.     

Optimization of flocculation conditions for kaolin suspension using the composite flocculant of MBFGA1 and PAC by response surface methodology

The response surface methodology (RSM) was employed to study the treatment of kaolin suspension by the composite flocculant of MBFGA1 and PAC. And the two quadratic models of the five factors were established with the flocculating rate and floc size as the target responses. The optimal flocculating conditions are MBFGA1 99.75 mg/L, PAC 121 mg/L, pH 7.3, CaCl₂ 27 mg/L and the top speed of stir 163 rpm, respectively. That was obtained from the compromised results of two desirable responses, flocculating rate as 100% and floc size as 0.7 mm which were deduced from the frequency of responses. By means of Zeta potential measurement and experiment of flocculating process, it could be concluded that PAC has more capability on changing the potential of colloid and MBFGA1 is good at absorption and bridge effect. The composite of two kinds of predominance makes a significant sense on enhancing flocculating rate, reducing flocculent costs and decreasing secondary pollution.     

Optimization of ultrasonic-stimulated solvent extraction of sinigrin from Indian mustard seed (Brassica Juncea L.) using response surface methodology

Introduction – Sinigrin, a major glucosinolate present in Indian mustard (Brassica juncea L.) seeds as the precursor of the anticancer compound allyl isothiocyanate, shows a wide range of biological activities. It's necessary to optimize the extraction methods and conditions, in order to improve the extraction productivity and save raw material. Objective – To systemically investigate and optimize the most important factors affected the productivity of sinigrin in the process of extraction using response surface methodology. Methodology – The ranges of three main factors including the ethanol concentration, extraction time and extraction temperature were selected by the one‐factor‐at‐a‐time method. The conditions of ultrasonic‐stimulated extraction of sinigrin from defatted Indian mustard seed powder were optimized by Box‐Behnken design to obtain the maximum productivity. Result – The predicted productivity (3.81%) was obtained using 57% ethanol concentration at 81°C for 60 min, with the coefficient of the model R² > 0.96 (n = 17). The actual productivity (3.84 ± 0.02%) of sinigrin under the optimized condition was increased by 70.67% compared with the result of conventional extraction. Meanwhile, HPLC, UV and IR were applied to examine if there is a difference between the ultrasonic‐stimulated solvent extraction and conventional extraction, and the improvement of productivity of sinigrin depended on the destruction of cell wall caused by the elimination of outer pectinous material was explained by SEM and composition content analysis. Conclusion – The ultrasonic‐stimulated solvent extraction was suggested to be a promising method to improve the productivity of sinigrin. And the results demonstrated that sinigrin productivity may be related to pectinous materials existed in the seeds. Copyright © 2010 John Wiley & Sons, Ltd.     

Process optimization of an auger pyrolyzer with heat carrier using response surface methodology

A 1 kg/h auger reactor utilizing mechanical mixing of steel shot heat carrier was used to pyrolyze red oak wood biomass. Response surface methodology was employed using a circumscribed central composite design of experiments to optimize the system. Factors investigated were: heat carrier inlet temperature and mass flow rate, rotational speed of screws in the reactor, and volumetric flow rate of sweep gas. Conditions for maximum bio-oil and minimum char yields were high flow rate of sweep gas (3.5 standard L/min), high heat carrier temperature (∼600 °C), high auger speeds (63 RPM) and high heat carrier mass flow rates (18 kg/h). Regression models for bio-oil and char yields are described including identification of a novel interaction effect between heat carrier mass flow rate and auger speed. Results suggest that auger reactors, which are rarely described in literature, are well suited for bio-oil production. The reactor achieved liquid yields greater than 73 wt.%.     

Optimization of conditions for acid protease partitioning and purification in aqueous two-phase systems using response surface methodology

Aspergillopepsin I, an acid protease, was purified using an aqueous two-phase system that comprised various combinations of polyethylene glycol (PEG), NaH₂PO₄ and NaCl. Partition of the enzyme depended upon the molecular mass of the PEG and the presence of NaCl. With PEG 1500, 4000 and 6000, the partition coefficients were increased by 1,500-, 1,800- and 560-fold compared to values without NaCl. The presence of NaCl (8.75%, w/w) increased purification by 3.8, 9.5 and 2.8 times into these respective PEGs. The optimal aqueous two-phase system for acid protease purification was developed using response surface methodology. This system contained 17.3% of PEG 4000 (w/w), 15% NaH₂PO₄ (w/w) and 8.75% NaCl (w/w) and provided the best partition coefficient (Ke > 1,100) and yield over 99% in the same phase. The optimal ATPS purification factor of acid protease was over 5.     

响应面法优化细菌EHB01对铜绿微囊藻(Microcystis aeruginosa)的溶藻条件

【背景】水体富营养化导致的蓝藻水华对淡水资源造成了严重污染。利用环境友好型的溶藻菌可有效控制蓝藻的生长,是防治蓝藻水华形成的有效途径之一。【目的】优化溶藻细菌EHB01对铜绿微囊藻(Microcystis aeruginosa)的溶藻条件,以期为治理蓝藻水华污染提供高效的溶藻菌制剂。【方法】采用单因素试验对溶藻的发酵液浓度、温度、光照以及C:N和N:P进行分析,并对溶藻细菌EHB01发酵液的碳源、氮源和p H进行优化。基于单因素试验,选用中心组合试验设计(central composite design,CCD)确定关键因子的最佳数量水平,并以Desig-Expert 8.0.5进行回归分析,通过响应面分析获得溶藻效果最佳的参数。【结果】发酵液浓度对溶藻率的影响表现为持续上升;温度对溶藻率表现为先上升后下降;而光照、C:N和N:P均对细菌EHB01发酵液溶藻率的影响表现为先降低后上升的趋势。溶藻细菌EHB01发酵液所需的最佳碳源为蔗糖,氮源为硝酸钾,pH为7.5,优化条件下溶藻率达86.97%,与优化之前相比提高了21.72%。【结论】采用响应面法优化得出溶藻细菌EHB01发酵液最优的...     

Optimal production of sulphuric acid by Thiobacillus thiooxidans using response surface methodology

Response surface methodology was applied to determine the optimal medium composition for sulphuric acid production by an indigenous Thiobacillus thiooxidans. With a view to reducing the number of experiments and obtaining the mutual interactions between the variables, a 2⁴ full-factorial central composite design was employed for experimental design and analysis of the results. Four independent variables, KH₂PO₄, (NH₄)₂SO₄, MgSO₄ and elemental sulphur, in the growth medium were tested. Elemental sulphur was found to exhibit positive correlation with the sulphuric acid yield, whereas the other three variables showed no significant effect. No mutual interactions were found between elemental sulphur and each of the other three variables. The optimal composition of the growth medium to achieve the optimal production of sulphuric acid was determined as follows (g/l): KH₂PO₄=3.5, (NH₄)₂SO₄=4.9, MgSO₄=0.7 and elemental sulphur=23.7. The corresponding sulphuric acid production and dry cell weight were 38 662 ppm and 0.7 g/l, which are about 2.6- and 1.75-fold increase, respectively, compared with those using the conventional T. thiooxidans optimum growth medium.     

Development of tea tree oil-loaded liposomal formulation using response surface methodology

Abstract

The aim of this study is to prepare tea tree oil liposome (TTOL) and optimize the preparation condition by single factor experiment and statistical design. TTOL was prepared using a thin-film hydration with the combination of sonication method and the preparation conditions of TTOL were optimized with response surface methodology (RSM). The optimal preparation conditions for TTOL by response surface methodology were as follows: the mass ratio of PC and Cho 5.51, TTO concentration 1.21% (v/v) and Tween 80 concentration 0.79% (v/v). The response surface analysis showed that the significant (p?<?0.05) second-order polynomial regression equations successfully fitted for all dependent variables with no significant (p?>?0.05) lack of fit for the reduced models. Furthermore, the interaction of the mass ratio of PC/Cho and TTO concentration had a significant effect. The amounts of Tween 80 required were also reduced with RSM. Under these conditions, the experimental encapsulation efficiency of TTOL was 97.81?±?0.33%, which was close with the predicted value. Therefore, the optimized preparation condition was very reliable. The increased entrapment efficiency would significantly improve the TTO stability and bioavailability.     

Optimization of pectin extraction from lemon by-product with acidified date juice using response surface methodology

Response surface methodology was used to optimize pectin recovery from lemon by-product using an acidified date juice as extraction solution. When enriched in pectin, this latter can be useful for preparation of date-lemon jelly. The effects of three parameters namely temperature, pH and extraction time, on pectin extraction were studied. The fitted mathematical model allowed us to plot response surfaces as well as isoresponse curves and to determine optimal extraction conditions. Results clearly indicated that the temperature was the main factor influencing the pectin yield which increased with temperature and time or decreasing pH. The selected optimal conditions were: temperature 84.34 °C; extraction time 3 h 34 min and pH 2.8. These conditions yielded about 11.21% of pectin versus 10.89% for the predicted value.     

Optimization of medium composition for butyric acid production by Clostridium thermobutyricum using response surface methodology

The optimal medium for butyric acid production by Clostridium thermobutyricum in a shake flask culture was studied using statistical experimental design and analysis. The optimal composition of the fermentation medium for maximum butyric acid yield, as determined on the basis of a three-level four-factor Box-Behnken design (BBD), was obtained by response surface methodology (RSM). The high correlation between the predicted and observed values indicated the validity of the model. A maximum butyric acid yield of 12.05 g/l was obtained at K₂HPO₄ 7.2 g/l, 34.9 g/l glucose, 20 g/l yeast extract, and 15 g/l acetate, which compared well to the predicated production of 12.13 g/l.     

Formulation and optimization of controlled release mucoadhesive tablets of atenolol using response surface methodology

The aim of the current study was to design oral controlled release mucoadhesive compressed hydrophilic matrices of atenolol and to optimize the drug release profile and bioadhesion using response surface methodology. Tablets were prepared by direct compression and evaluated for bioadhesive strength and in vitro dissolution parameters. A central composite design for 2 factors at 3 levels each was employed to systematically optimize drug release profile and bioadhesive strength. Carbopol 934P and sodium carboxymethylcellulose were taken as the independent variables. Response surface plots and contour plots were drawn, and optimum formulations were selected by feasibility and grid searches. Compressed matrices exhibited non-Fickian drug release kinetics approaching zero-order, as the value of release rate exponent (n) varied between 0.6672 and 0.8646, resulting in regulated and complete release until 24 hours. Both the polymers had significant effect on the bioadhesive strength of the tablets, measured as force of detachment against porcine gastric mucosa (P<.001). Polynomial mathematical models, generated for various response variables using multiple linear regression analysis, were found to be statistically significant (P<.01). Validation of optimization study, performed using 8 confirmatory runs, indicated very high degree of prognostic ability of response surface methodology, with mean percentage error (±SD) as −0.0072±1.087. Besides unraveling the effect of the 2 factors on the various response variables, the study helped in finding the optimum formulation with excellent bioadhesive strength and controlled release. Published: January 13, 2006     

响应面法对超临界CO_2萃取茶籽仁油的工艺优化

为了保证茶籽油的原生态品质,研究了茶籽仁油的超临界CO2萃取技术,并运用响应面法对其萃取压力、温度和时间等工艺条件进行了优化分析,得到的最佳工艺条件是在33 MPa压力和43℃温度下连续萃取时间2 h。此条件下的萃取得率为39.6%、出油效率达86.5%,所得茶籽油只需简单的脱酸处理即达到国标GB11765—2003规定的压榨一级茶籽油水平。     

Optimization of pancreatic lipase inhibition by Cudrania tricuspidata fruits using response surface methodology

The fruits of Cudrania tricuspidata (Carr.) Bur. (Moraceae) significantly inhibited pancreatic lipase, which plays a key role in fat absorption. Optimization of extraction conditions with minimum pancreatic lipase activity and maximum yield was determined using response surface methodology with three-level-three-factor Box–Behnken design (BBD). Regression analysis showed a good fit of the experimental data and the optimal condition was obtained as ethanol concentration, 74.5%; temperature 61.9 °C and extraction time, 13.5 h. The pancreatic lipase activity and extraction yield under optimal conditions were found to be 65.5% and 54.0%, respectively, which were well matched with the predicted value of 65.8% and 47.1%. Further fractionation of C. tricuspidata extract resulted in the isolation of compound 1, which was identified as 5,7,4′-trihydroxy-6,8-diprenylisoflavone. It inhibited pancreatic lipase activity with IC₅₀ value of 65.0 μM. HPLC analysis suggested positive correlation between pancreatic lipase inhibition and 5,7,4′-trihydroxy-6,8-diprenylisoflavone of C. tricuspidata fruits.