Box-Behnken Response Surface Method Research Articles

Viscosity Reduction of Indian Heavy Crude Oil by Emulsification to O/W Emulsion Using Polysorbate‐81

AbstractPipeline transportation is the most convenient means of transportation of crude oil continuously and economically from production site to refinery. However, transportation of heavy crude oil (HCO) through pipelines is difficult due to its high viscosity. The high viscosity of heavy crude oil is mainly due to the presence of poly‐aromatic compounds like resins and asphaltenes. Emulsification of HCO using surfactant is believed to be the most favorable technique to reduce the viscosity of HCO for efficient pipeline transport. In the present study, oil‐in‐water (O/W) emulsion has been formulated using a non‐ionic surfactant Polyoxyethylene (5) sorbitan monooleate (PS‐81) at different pH, surfactant concentration, and oil content. Box–Behnken response surface method has been used to optimize two responses, apparent viscosity and emulsion stability index (ESI). The optimal values of the parameters found are 75%v/v oil content, 2.5%w/v surfactant concentration, and pH value of 7 at which experimental value of emulsion viscosity is 0.2162 Pa·s, at 150 RPM, with a reduction of viscosity by 95.8% and having ESI of 98.16 after 24 h at 30°C.

Enhanced O-succinyl-l-homoserine production by recombinant Escherichia coli ΔIJBB*TrcmetL/pTrc-metAfbr -Trc-thrAfbr -yjeH via multilevel fermentation optimization.

Constructing a strain with high yield of O-succinyl-l-homoserine (OSH) and improving the titre through multilevel fermentation optimization. OSH high-yielding strain was first constructed by deleting the thrB gene to block the threonine biosynthesis. Single-factor experiment was carried out, where a Plackett-Burman design was used to screen out three factors (glucose, yeast and threonine) from the original 11 factors that affected the titre of OSH. The Box-Behnken response surface method was used to optimize the fermentation conditions. Through gene editing and medium optimization, the titre of OSH increased from 7·20 to 8·70gl-1 in 500ml flask. Furthermore, the fermentation process and fed-batch fermentation conditions including pH, temperature, feeding strategy and feeding medium were investigated and optimized. Under the optimal conditions, the titre of OSH reached 102·5gl-1 , which is 5·6 times higher than before (15·6gl-1 ). O-succinyl-l-homoserine fermentation process was established and the combination of response surface methodology and metabolic pathway analysis effectively improved the titre of OSH. In this study, the titre of OSH reached the needs for industrial production and the metabolic pathway of OSH was demonstrated for further optimization.

Optimization of Process Parameters of Rhamnolipid Treatment of Oily Sludge Based on Response Surface Methodology.

Oily sludge is a hazardous waste. If not handled properly, it can not only pollute the environment but also endanger human health. This study is the first to use a response surface method to optimize the main parameters of rhamnolipid-based recovery of oil from oily sludge. Using rhamnolipids as the cleaning agent and the oil recovery fraction as the evaluation index, the factors affecting the cleaning efficiency of oily sludge were optimized. The aforementioned sludge was obtained from the Tarim Oilfield. A single-factor experiment was conducted to determine the optimal range of the dosage, liquid–solid ratio, pH value, and time. The Box–Behnken response surface method was used to investigate the influence of each variable on the residual oil fraction of the oily sludge, and the dosage, pH value, and time were found to have a significant impact. The model optimization results show that the best process conditions for rhamnolipid-based recovery of oil are as follows: rhamnolipid dosage = 167.785 mg/L; liquid–solid ratio = 4.589:1; pH = 9.618; time = 1.627 h. Under optimal conditions, the model-predicted oil recovery fraction and the actual oil recovery fraction were 85.15 and 82.56%, respectively; the relative error between the predicted and the actual values was 2.59%. These results indicate that the model results are reliable. The solid residue after the cleaning was also analyzed to gain an in-depth understanding of the cleaning process. This study determined the feasibility of a rhamnolipid-based solution for the treatment of oily sludge and oil-contaminated soil.

Extraction of Flavonoids from Scutellariae Radix using Ultrasound-Assisted Deep Eutectic Solvents and Evaluation of Their Anti-Inflammatory Activities.

Deep eutectic solvents (DESs) play important roles in the extraction of active constituents in traditional Chinese medicine. Ultrasound-assisted DES has been used to extract flavonoids from Scutellaria baicalensis. Using the contents of scutellarin, baicalin, baicalein, wogonoside, wogonin, and oroxylin A as quantitative indices, different kinds of DESs have been optimized for extraction and betaine/acetic acid has shown the highest yield. The Box–Behnken response surface method (RSM) was utilized to select the extraction conditions with the highest yields. The optimal extraction conditions were as follows: the molar ratio of betaine/acetic acid was 1:4, the water content was 40%, the solid/liquid ratio was 1:100 g/mL, the extraction temperature was 52 °C, and the extraction time was 23 min. Compared with traditional reflux extraction using 70% ethanol as the solvent, ultrasound-assisted DES has a shorter extraction time and higher yields. Furthermore, anti-inflammatory activities of the two extracts by ultrasound-assisted DES and reflux were compared using RAW264.7 cells and the methyl thiazolyl tetrazolium (MTT) method, and they showed equal anti-inflammatory activities. The results demonstrated that the ultrasound-assisted DES method for extraction of flavonoids from scutellariae radix is simple, green, efficient, and reproducible. This research provides good method guides for the rapid and efficient extraction of flavonoids from natural sources.

Optimization of alkali-catalyzed transesterification of rubber oil for biodiesel production & its impact on engine performance

Abstract Rubber (Hevea brasilienis) is a plantation crop grown in various regions of India. It is a non-edible oil source and has excellent potential for being a biodiesel feedstock. The major problem with crude rubber seed oil is its high free fatty acid (FFA) content (37.46%). The present study has used the Box-Behnken response surface method to minimize the FFA content of the oil. FFA content of 1.31% was obtained with alcohol to oil molar ratio of 6.652:1 and 0.5 wt% of H2SO4 catalyst at a reaction temperature of 63.75 °C in 50 min. The results of engine testing indicated a decrease in fuel consumption by 50.23% for RB10 and 47.74% for RB20 when compared with neat diesel. The thermal efficiency was reduced by 12.16% for RB10 and 14.74% for RB20. The emission analysis revealed that HC emissions were increased by 22.3% for RB10 and by 41.72% for RB20. There was a decrease in NOx emissions by 21.5% for RB10 and by 21.7% for RB20 while the CO2 emissions were reduced by 46.3% for RB10 and 49.54% for RB20 at full loading. The CO emissions were increased by 25% and 37.5% for RB10 and, respectively, when compared with diesel.

Goat milk Kefir with ACE inhibitory activity: Preparation and storage stability evaluation

In this study, the Box–Behnken response surface method was used to optimize the conditions of Kefir grain fermented goat milk, and the angiotensin-converting enzyme (ACE, EC 3.4.15.1) inhibitory activity and sensory evaluation were improved. The results showed that the optimum fermentation conditions were 23 hr fermentation at 24°C, and the inoculum size was 2.5%. Under optimal conditions, the ACE inhibition rate increased significantly from 73.34 ± 0.37% to 85.97 ± 0.62% (p < .05), and the sensory evaluation increased significantly from 75.83 ± 0.46 to 84.65 ± 0.76 (p < .05), close to the predicted values of 86.54% and 85.20%. The storage stability of Kefir goat milk was studied. The results showed that there was a post-acidification process during the 14-day preservation of Kefir goat milk, with the acidity increasing, the pH value decreasing, and the sensory evaluation value increasing. This study can provide a good reference for the preparation and storage of goat milk Kefir. Practical applications In recent years, Kefir's health function has been found by more and more researchers, so it has gained the favor of the majority of consumers. In this study, response surface method was used to optimize the technological parameters of Kefir grain fermented goat milk and to explore the stability of Kefir milk during storage. The storage stability of Kefir is better.

Optimization of Culture Conditions for Amoxicillin Degrading Bacteria Screened from Pig Manure.

(1) Objective: The objective of this study was to screen amoxicillin (AMX)-degrading bacterial strains in pig manure and optimize the fermentation conditions for these strains to achieve high fermentation rate, which can provide an effective way for the practical application of bacterial strains as antibiotic-degrading bacterial in treating livestock waste for antibiotic residues. (2) Methods: Antibiotic susceptibility tests and high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) were employed to screen AMX-degrading bacterial strains in pig manure. The culture conditions were optimized for AMX-degrading bacterial strains using Plackeet–Burman design (PBD), the steepest ascent design, and the response surface methods, coupled with the Box–Behnken design (BBD). The effects of culture time, temperature, rotator (mixing) speed, inoculum level, and initial pH value on the growth of AMX-degrading strains were investigated. Experimental data obtained from BBD were utilized to generate a second-order polynomial regression model for evaluating the effects of the tested variables on the optical density at 600 nm (OD600) of culture solutions as the growth indicator for the screened AMX-degrading strains. (3) Results: The initial pH, culture time, and the inoculum level had significant effects on the OD600 value (growth) of the screened AMX-degrading strains. The initial pH value was found to be the most critical factor influencing the growth of bacteria. The optimized culture condition for the bacterial growth determined by the response surface methodology was: the initial pH of 6.9, culture time of 52 h, and inoculum level of 2%. The average OD value of 12 different fermentation conditions in the initial fermentation tests in this study was 1.72 and the optimization resulted in an OD value of 3.00. The verification experiment resulted in an OD value of 2.94, which confirmed the adequacy of the optimization model for the determining the optimal culture condition. (4) Conclusions: The growth of the screened strain of AMX-degrading bacteria could be optimized by changing the fermentation conditions. The optimization could be achieved by using the Box–Behnken response surface method and Plackett–Burman experimental design.

Efficient removal of As(V) from simulated arsenic‐contaminated wastewater via a novel metal–organic framework material: Synthesis, structure, and response surface methodology

A novel metal–organic framework material {[N(C2H5)3][Zn2(ptmda)2(μ2‐H2O)]·(H2O)0.5}n {GUT‐3; H2ptmda is 4,4′‐([p‐tolylazanediyl]bis [methylene])dibenzoic acid} was successfully synthesized using the hydrothermal method and characterized by X‐ray diffraction, Fourier transform infrared spectroscopy, and X‐ray photoelectron spectroscopy. GUT‐3 has a two‐dimensional network based on dinuclear [Zn2(ptmda)2(μ2‐H2O)]− building units which formed an eightfold interpenetration network in GUT‐3 molecules. Hirshfeld surface analysis revealed that H–H, C–H, and O–H bonds accounted for the majority of intermolecular interactions. Moreover, the interactions between GUT‐3 and As(V) – the form of As(V) is AsO43− – were analyzed in aqueous solutions in a batch system to study the effect of pH, concentration, adsorbent dose, adsorption time, adsorption temperature, and shaking speed. The kinetic and isotherm data of arsenic adsorption on GUT‐3 were accurately modeled by pseudo‐second‐order, Langmuir (qm = 33.91 mg/g), and Freundlich models. The Box–Behnken response surface method was used to optimize the adsorption conditions of As(V) from the simulated arsenic‐contaminated wastewater. The effect of various experimental parameters and optimal experimental conditions was ascertained using the quadratic model.

Optimization of Fermentation Process Enhancing Quality of Dandelion Black Tea on the Functional Components, Activity and Sensory Quality

The fermentation technology of dandelion black tea was optimized by Box-Behnken response surface method. Combined with sensory evaluation and biochemical analysis, the effects of fermentation conditions such as temperature, time and humidity on the functio...

Optimization of wear performance on aluminium die cast A360-M1 master alloy using response surface method

Abstract Aluminium die cast A360-M1 master alloy with mass fraction (0.4 wt%) Al-5%Ti-1% B light metal matrix composite (LMMC) was prepared using the stir casting method. A three-level principle composite design test was developed using the boxbehnken response surface methodology. Variation in parameters such as load, sliding distance and sliding velocity were made in the range of 10–30 N, 500–1500 m, and 0.5–1.5 m/s respectively. Tribological dry sliding wear tests were performed as per the experimental design, using a pin-on disc setup at room temperature. Analysis of variance (ANOVA) was applied to study the impact of process parameters and their interactions viz., Load, sliding distance, sliding velocity on specific wear rate (SWR), frictional force (FF) and coefficient of friction (COF). The objective of this research is to recognize the parameters that significantly affect the output features such as specific wear rate, friction force, and COF of the aluminium die cast A360-M1 master alloy light metal matrix composites. Further, a mathematical model has been expressed by relating the boxbehnken response surface method in order to estimate the tribological characteristics. This work shows this A360-M1 master demonstrating the minimization of SWR, FF, and COF with response of load, sliding distance, and sliding velocity.

Application of Agaricus bisporus industrial wastewater to produce the biomass of Pichia burtonii.

By using Plackett-Burman combined with Box-Behnken design, the fermentation conditions of Pichia burtonii using Agaricus bisporus industrial wastewater as culture medium were optimized. The biomass of P. burtonii in the fermentation broth was analyzed by multispectral imaging flow cytometry. Plackett-Burman design was used to screen out three factors from six factors affecting the biomass of P. burtonii as major factors. The Box-Behnken response surface method was used to optimize the interaction of the three main factors to predict the optimal fermentation conditions. The significant factors affecting the biomass of P. burtonii, such as shaking speed, solubility and culture temperature, were screened. The optimum conditions for P. burtonii were as follows: a shaking speed of 265 rmp, a solubility of 8%, a culture temperature of 25 °C, an initial pH of 6.0, an inoculation amount of 8%, and an amount of 30 mL liquid in 250 mL, and the total living yeast can reach 1.27 ± 0.02 × 108 Obj/mL, which was within the 95% confidence interval of the predicted model (1.08-1.32 × 108 Obj/mL).

Response surface based experimental analysis and thermal resistance model of a thermoelectric power generation system

In this work, a response surface analysis is carried out on an experimental setup of a combined two-phase flow thermosyphon and thermoelectric generator (TEG) system. Three-level Box-Behnken response surface method is adopted for the design of experiments, and analysis of variance is carried out to gauge the contribution of operating parameters on various performance parameters. Effects of operating parameters such as working pressure, filling ratio, evaporator length, and evaporator temperature are studied. The performance of the system itself is gauged concerning the maximum power obtained, open circuit voltage and short circuit current. With an increase in vacuum pressure and evaporator temperature, performance parameters are found to increase. However, performance parameters under the influence of filling ratio and evaporator length first decrease and then increase due to uneven variation in evaporation rate of working fluid. Experiments also reveal that the performance of the thermosyphon-assisted TEG system is mainly governed by pressure and evaporator temperature, whereas filling ratio and evaporator length have relatively lesser influence.

Plackett-Burman design and response surface optimization of conditions for culturing Saccharomyces cerevisiae in Agaricus bisporus industrial wastewater.

The Agaricus bisporus industrial wastewater that contains a variety of nutrients which could be used as culture for some beneficial microbiology will be one threat to our environment if the wastewater doesn&rsquo;t be comprehensively utilized. Plackett-Burman is the rapid and concise ways of screening the main effective factors. Box-Behnken response surface method is used to optimize interactions between the three main factors and predict optimal fermentation conditions. This study is aimed to select the main influence fac- tors and optimize the conditions for culturing Saccharomyces cerevisiae in A. bisporus industrial wastewater by Plackett-Burman design and Box-Behnken response surface method. We analyzed the total number of living S. cerevisiae in the fermentation broth using multispectral imaging flow cytometry. Plackett-Burman design was used to screen out three factors from the original six factors of processing wastewater concentration, initial pH, inoculum size, liquid volume, culture temperature, and rotation speed that affected the total number of viable S. cerevisiae. Factors significantly affecting the total number of viable S. cerevisiae, including culturing temperature, processing wastewater concentration, and initial pH were investigated. Result. The results indicated that culture temperature (p = 0.0007) and pH (p = 0.0344) as negative factor and concentration (p = 0.0080) as positive effect were the significant factors affecting the total number of S. cere- visiae, inoculum (p = 0.1237) and shaking speed (p = 0.2112) as positive effect and loaded liquid (p = 0.4811) as negative factor were important fact. nd. The Agaricus bisporus industrial wastewater that contains a variety of nutrients which could be used as culture for some beneficial microbiology will be one threat to our environment if the wastewater doesn&rsquo;t be comprehensively utilized. Plackett-Burman is the rapid and concise ways of screening the main effective factors. Box-Behnken response surface method is used to optimize interactions between the three main factors and predict optimal fermentation conditions. This study is aimed to select the main influence fac- tors and optimize the conditions for culturing Saccharomyces cerevisiae in A. bisporus industrial wastewater by Plackett-Burman design and Box-Behnken response surface method. Material and methods. We analyzed the total number of living S. cerevisiae in the fermentation broth using multispectral imaging flow cytometry. Plackett-Burman design was used to screen out three factors from the original six factors of processing wastewater concentration, initial pH, inoculum size, liquid volume, culture temperature, and rotation speed that affected the total number of viable S. cerevisiae. Factors significantly affecting the total number of viable S. cerevisiae, including culturing temperature, processing wastewater concentration, and initial pH were investigated. Result. The results indicated that culture temperature (p = 0.0007) and pH (p = 0.0344) as negative factor and concentration (p = 0.0080) as positive effect were the significant factors affecting the total number of S. cere- visiae, inoculum (p = 0.1237) and shaking speed (p = 0.2112) as positive effect and loaded liquid (p = 0.4811) as negative factor were important factors. The optimum conditions for S. cerevisiae fermentation in A. bi- sporus wastewater were a rotational speed of 150 rpm, a culture temperature of 25&deg;C, an initial pH of 6.0,&nbsp;&nbsp; a concentration of 8.4%, a inoculation volume of 8%, and a 100 mL liquid volume in a 250 mL flask, a culture time of 48 h. Under these conditions, the concentration of total viable yeast reached 1.04 &plusmn;0.02 &times; 108 Obj/mL which was at the 95% confidence interval of predicted model (0.89&ndash;1.14 &times; 108 Obj/mL). The experimental model is reliable and the experimental results are of good stability. Variance analysis is performed to determine the adequacy and significance of the linear model. Thus, Plackett-Burman.

Process Parameter Correlation in Low Pressure Hydro Forming of 6063-O Aluminium Tubes

The study is performed to investigate the effects of low pressure tubular hydro-forming process parameters on the protrusion height and percentage change in wall thickness of 6063-O aluminium tubes. A mathematical correlation for these parameters are developed employing Box-Behnken response surface method. The required responses are obtained using a developed finite element model considering elastic-plastic material behaviour and validated. It is inferred that the higher friction induced on the contact surfaces of the components significantly influences the geometrical dimensions of final product. Also, it is suggested that the components require sufficient time period to undergo severe plastic deformation that can be provided by slower rate of loading during process. DOI: http://dx.doi.org/10.5755/j01.mech.25.1.20326

Optimization of The Extraction Process of Polysaccharide from Schisandra Chinensis (Turcz.) Baill

Based on Box-Behnken response surface method, it utilizes ultrasound-microwave synergistic effect to extract polysaccharide of Schisandra chinensis by taking the polysaccharide extraction ratio of fructus schisandra. On the basis of designing single factor experiment, it selects the extraction temperature, microwave power, ultrasonic wave power, feed liquid ratio and reaction time as the review factors and further determines the optimal extraction process by the response surface method: the extraction temperature is 65°C; the microwave power is 550W; the ultrasonic wave power is 60W; the reaction time is 15min; the feed liquid ratio is 1:25; under such condition, the polysaccharide extraction ratio is 13.23%.

Response surface optimization of conditions for culturing Azotobacter chroococcum in Agaricus bisporus industrial wastewater.

In the present study, the conditions for Azotobacter chroococcum fermentation using Agaricus bisporus wastewater as the culture medium were optimized. We analyzed the total number of living A. chroococcum in the fermentation broth, using multispectral imaging flow cytometry. Single-factor experiments were carried out, where a Plackett-Burman design was used to screen out three factors from the original six processing factors wastewater solubility, initial pH, inoculum size, liquid volume, culture temperature, and rotation speed that affected the total number of viable A. chroococcum. The Box-Behnken response surface method was used to optimize the interactions between the three main factors and to predict the optimal fermentation conditions. Factors significantly affecting the total number of viable A. chroococcum, including rotation speed, wastewater solubility, and culture temperature, were investigated. The optimum conditions for A. chroococcum fermentation in A. bisporus wastewater were a rotation speed of 200 rpm, a solubility of 0.25%, a culture temperature of 26°C, an initial pH of 6.8, a 5% inoculation volume, a culture time of 48 h, and a liquid volume of 120 mL in a 250 mL flask. Under these conditions, the concentration of total viable bacteria reached 4.29 ± 0.02 ✕ 107 Obj/mL A. bisporus wastewater can be used for the cultivation of A. chroococcum.

Concentration of Polyphenolic Compounds from Grape Seed by Nanofiltration Technology

Abstract In order to evaluate the applicability of nanofiltration (NF) polyphenols determined by total phenolic compounds content with application of Folin method in grape seed extract, response surface analysis methodology was used to analyze the concentration process with the indices of membrane fouling and antioxidant activity. In addition to the influencing factors of molecular weight cut-off (MWCO) of NF membrane, procyanidin concentration and pH value, the evaluation index of procyanidin rejection was taken into account for the process optimization by Box-Behnken response surface method on the basis of single factor test. According to Box-Behnken central composite experiment design, the optimal conditions were obtained as follows: NF MWCO of 400 Da, 27.66 μg/mL procyanidins, and pH 5.20. The predicted rejection of procyanidins under the optimum conditions was 97.17% and the experimental value was 96.36 ± 0.87%, which was in accordance with the predicted value. The experimental value of total polyphenolic content (TPC) was 91.09 ± 0.46%. The antioxidant activity was increased about 2.24 times and the antioxidant activity was correlated with the procyanidin content. Moreover, it was easy to clean membrane fouling. The NF was an effective method for concentrating polyphenolic compounds from grape seed extracts without the loss of polyphenolic compounds. The agricultural product utilization was improved greatly and the power consumption was decreased by the NF technology.

Preparation and quality evaluation of volatile oil from Acori Tatarinowii Rhizoma self-nanoemulsion

In order to increase the solubility of volatile oil from Acori Tatarinowii Rhizoma, this study was to prepare self-nanoemulsion of volatile oil from Acori Tatarinowii Rhizoma . The prescriptions were preliminarily screened by miscibility studies, excipient compatibility tests, and pseudo-ternary phase diagrams, and then the optimal formulation was obtained by using the Box-Behnken response surface method, with particle size and drug-loading rate as the indicators. The self-nanoemulsion prepared by optimal prescription was characterized and evaluated for in vitro dissolution. The results showed that the optimal prescription for this volatile oil self-nanoemulsion was as follows: 41.7% volatile oil, 46.8% Tween-80, and 11.5% PEG-400. The prepared self-nanoemulsion was clear and transparent, with drug-loading of (192.77±1.64) mg·g⁻¹, particle diameter of (53.20±0.94) nm, polydispersity index of 0.230± 0.013, and Zeta potential of (-12.2±0.7) mV. The in vitro dissolution of self-nanoemulsion was higher than that of volatile oil. In this research, volatile oil served as the oil phase in self-nanoemulsion, so the prescription was simpler and the drug loading rate was higher. The prepared self-nanoemulsion complied with the relevant quality requirements, providing a reference for the preparation of volatile oil formulations.

Highly efficient treatment of real benzene dye intermediate wastewater by simple limestone and lime neutralization-coagulation with improved Fenton oxidation.

Multistage Fenton oxidation is a favored method for the treatment of benzene dye intermediate (BDI) wastewater, but the pH adjustments required after each stage of the Fenton process with a simple way is still a challenge. Limestone pretreatment and lime neutralization-coagulation were used to solve the problem in multistage Fenton process. First, we determined the optimal conditions of Fenton oxidation using the Box-Behnken response surface method. Limestone pretreatment before the multistage Fenton process allowed for simultaneous pH adjustment and 14.15% COD removal. Most notably, the lime cream neutralization-coagulation process effectively adjusted the pH after each stage of the Fenton process. The optimum CaO particle size, lime mass fraction, mixing time, and stirring speed were determined by orthogonal tests. COD removal (89.23%) was obtained when lime cream neutralization-coagulation was applied to the three-staged Fenton process, while only 58.57% COD removal was obtained by the unadjusted single-staged Fenton process. The COD and wastewater color were reduced from 10,600mg/L and 12,200 multiples to 495mg/L and 20 multiples, respectively, using the adjusted process. This improved method provides a promising cost-effective way to efficiently treat real BDI wastewater.

Study on rolling drying granulation of Rebiqing granules

Objective Rebiqing granules were prepared and the rolling drying granulation process parameters were optimized. Methods According to the previous knowledge and experience, the feed rate, pressure and speed of rolling were used as the factors for investigation, and the primary forming rate and the solubility of the Rebiqing granule were taken as the evaluation indexes, and the Box-Behnken response surface method was used to optimize the rolling drying granulation parameters. Results The optimum rolling drying granulation parameters were as follows: feed rate was 8.5 Hz, rolling pressure was 6.0 Mpa and rolling speed was 8.5 Hz. After continuous production of 3 batches of validation, the Rebiqing granules had high molding rate and good solubility. Conclusions The rolling drying granulation processes were optimized by the experimental design, which could improve the robustness of the processes and control the stability of the product quality. Key words: Technology improving (TCD); Rebiqing granules; Rolling drying granulation; Box-Behnken design-response surface methodology