Central Composite Design-response Surface Method Research Articles

Modeling and Optimization of Sisal Fiber Degradation Treatment by Calcined Bentonite for Cement Composite Materials

ABSTRACT The treatment of sisal fiber by pozzolanic materials like kaolin and silica-fume has been explored; however, no study has modeled and optimized the effect of sisal fiber degradation treatment using calcined bentonite. Therefore, the present study investigate the effects of treating sisal fiber with different doses of calcined bentonite, bentonite calcination temperatures, and times on fiber breaking load, degradation resistance, and water absorption using the central composite design-response surface method (CCD-RSM). The best performance of the optimum treated sisal fiber selected from the CCD-RSM based on the established goal of maximizing breaking load and degradation resistance with minimum water absorption, it was obtained a calcined bentonite dose of 30.067%, a bentonite calcination temperature of 800°C, and a calcination time of 179.99 min. Based on these factors, experimentally found sisal fiber breaking load 12.87 N, degradation resistance 98.44%, and water absorption 39.05%, all are within the 95% confidence level compared to the optimum numerical suggested values. Hence, the optimum treated sisal fiber improved breaking load by 33.37% and degradation resistance by 98%, while it reduced water absorption by 60.95%, compared to raw sisal fiber. Besides these, the optimum treated sisal fiber exhibits higher surface roughness and lower porosity than the raw sisal fiber.

Design and Evaluation of Ophthalmic Thermosensitive In Situ Gel of Compound Salvia.

The compound Salvia Recipe has been shown to have a relatively significant curative effect in management of cardiovascular and cerebrovascular diseases. This work aimed to prepare a thermosensitive in situ gel (ISG) delivery system that utilizes Poloxamer 407, Poloxamer 188, and hydroxypropyl methylcellulose for ocular administration of the compound Salvia recipe to treat cardiovascular and cerebrovascular diseases. The central composite design-response surface method was utilized to improve the prescription of the gel. The formulated gel was characterized and assessed in terms of stability, retention time, in vitro release, rheology, ocular irritation, pharmacokinetics studies, and tissue distribution. The gel was a liquid solution at room temperature and became semisolid at physiological temperature, prolonging its stay time in the eye. Pharmacokinetics and tissue distribution experiments indicated that thermosensitive ISG had enhanced targeting of heart and brain tissues. Additionally, it could lower drug toxicity and side effects in the lungs and kidneys. The compound Salvia ophthalmic thermosensitive ISG is a promising drug delivery system for the management of cardiovascular and cerebrovascular illnesses.

Modelling and optimization of multiple replacement of supplementary cementitious materials for cement composite by response surface method

Supplementary cementitious materials are beneficial in improving performance and lessening the cement consumption with highly lessening CO2 emission. Many researchers used blast furnace slag, bentonite, and active limestone separately or two of them together to improve the performance of cementing materials, however, it is not well known how all react together in cement composite materials. So, the present study used modeling and optimizing the replacement of blast furnace slag, raw bentonite, and active limestone each by the doses of 0 to 20% to maximize strength and minimize the fresh bulk density of cementing materials by central composite design-response surface method (CCD-RSM). The results found, the employment of blast furnace slag, bentonite, and active limestone in the cement composite materials generally lessens the early strength compared to the control mixture. However, the replacement of blast furnace slag and active limestone by 20% significantly improves the 28-days compressive strength while employing raw bentonite by 20% reduced compressive strength by 6.45% compared to the control mixture. However, blending raw bentonite with active limestone by half improved the compressive strength. Besides these, the substitution of bentonite and active limestone reduces the fresh bulk density and flexural strength than the control mixture. Generally, the study optimized depending on the criteria of maximizing strength and minimizing fresh density and found the mix design replacement of blast furnace slag 1.01%, raw bentonite 5.30%, and active limestone 20% that improves 28 days compressive strength simultaneously reduces fresh bulk density in addition to replacing more than 54 different optimized design mix results.

Preparation and quality evaluation of total flavonoids microemulsion of "Pueraria lobata-Hovenia dulcis"

The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.

Study on the Performance and Mechanism of Cold-Recycled Asphalt Based on Permeable Recycling Agent.

In order to investigate the influence of recycling agent composition on the recycling effect of aged asphalt in the cold recycling process, the design and optimization of cold recycling agent composition were performed through the central composite design-response surface method combined with the dynamic shear rheometer (DSR) test and the bending beam rheometer (BBR) test. The molecular weight distribution and component changes in aged asphalt before and after the addition of a cold recycling agent were also analyzed by gel permeation chromatography (GPC) and hydrogen-flame ionization test. The results showed that the permeable cold recycling agent has a recycling effect on the aged asphalt, but its effectiveness is greatly affected by recycling agent composition. The best recycling effect was achieved when the ratio of aromatic oil and penetrant in the cold recycling agent was 61.2:38.8, respectively. In terms of the recycling agent and aromatic functional groups in the aromatic oil, the aromatics in the recycling agent are derived from the aromatic oils, and the penetrant is only fused and permeated with the aromatic oils. After the admixture of the cold recycling agent, the penetrant in the recycling agent allows the aromatic oil to enter the aged asphalt at room temperature. The light components volatilized by aging are replenished, allowing the aged asphalt to recover some of its properties.

Preparation of inorganic binder-stabilised material with iron tailings: strength formation and gradation optimisation

This study focuses on mechanical strength and gradation optimisation of inorganic binder-stabilised material with iron tailings for pavement engineering. The mechanical strength and compatibility of iron tailings mortar with various inorganic binders were explored. Mechanical strength formation of iron tailings mortar was analysed using hydration products, micromorphology and microstructures. Composition optimisation of inorganic binder-stabilised material with iron tailings was discussed using the central composite design-response surface method. Results showed that the mechanical strength formation of iron tailings mortar is primarily dependent on ettringite and calcium silicate hydrate (C–S–H) gels. Iron tailings mortars with an appropriate amount of lime or fly ash replacement of cement exhibit a denser structure and adequate pore structure distribution that help improve their mechanical properties compared with cement iron tailings mortars. To balance the amount of iron tailings and the strength of cement-stabilised material, optimal application conditions were proposed for different levels of highways.

Preparation of Cangyi nanoemulsion in situ gel and drug release mechanism of nasal mucosa in vitro

To prepare Cangyi nanoemulsion in situ gel and study its nasal mucosa release mechanism in vitro. After proper treatment of different drugs in the compound, the prescription of nanoemulsion was determined by pseudo-ternary phase diagram method. With the ratio of mixed emulsifier to oil phase [(S+COS)/O], the ratio of mixed emulsifier(K_m), the ratio of water phase to mixed emulsifier and oil phase[W/(S+COS+O)] as investigation factors and the normalized value(OD) as evaluation index, the prescription of Cangyi nanoemulsion was optimized by central composite design-response surface method. With the ratio of poloxamer 407(P407) and poloxamer 188(P188) as the investigation factors and the gelation temperature as the evaluation index, the in situ gel prescription of Cangyi nanoemulsion was optimized. The improved Franz diffusion cell was used to explore the nasal mucosa drug-release mechanism of Cangyi nanoemulsion in situ gel with oxymatrine, ferulic acid and salvianolic acid B content as indexes. The optimal prescription of Cangyi nanoemulsion in situ gel was as follows: 6.862% castor oil polyoxyl(EL), 4.262% absolute ethanol, 1.392% ethyl oleate, 7% P407 and 6% P188. The average pH was 5.55 and the average gelation temperature was 32.8 ℃. In vitro release studies showed that oxymatrine, ferulic acid and salvianolic acid B were released simultaneously and the drug release behavior was consistent with that in Higuchi model. The preparation process of Cangyi nanoemulsion in situ gel is stable, with suitable pH value, gelation temperature and viscosity. It has a certain slow-release effect, and can meet the needs of local nasal drug use.

Preparation and in vitro quality evaluation of curcumin supersaturated self-nanoemulsion

In order to improve the supersaturation and maintenance time of drug dispersion in curcumin self-nanoemulsion(CUR-SNEDDS), precipitation inhibitors(PPIs) were introduced to prepare curcumin supersaturated self-emulsion(CUR-SSNEDDS). The composition of CUR-SNEDDS prescriptions was selected through the solubility test, the compatibility of oil phase and surfactant, the investigation of the emulsifying ability of the surfactant and the drawing of the pseudo-ternary phase diagram. Analytic hierarchy process was used in combination with central composite design-response surface method to optimize the prescription. The type and dosage of precipitation inhibitors(PPIs) were selected to maintain the supersaturated concentration and duration of CUR in artificial gastrointestinal fluids. At the same time, polarizing microscope was used to evaluate the crystallization inhibition effect and the quality and in vitro release behavior of CUR-SSNEDDS. The prepared CUR-SSNEDDS prescription was capryol 90-kolliphor RH40-transcutol HP-Soluplus(7.93∶66.71∶25.36∶5), with the drug loading of(65.12±1.25) mg·g~(-1). CUR-SSNEDDS was transparent yellow, and the nanoemulsion droplets were spherical with uniform distribution. The emulsification time was(21.02±0.13) s, the average particle size was(57.03±0.35) nm, the polydispersity index(PDI) was(0.23 ± 0.01), and the Zeta potential was(-18.10±1.30) mV. CUR-SSNEDDS significantly inhibited the generation and growth of crystals after in vitro dilution. The supersaturation could be maintained above 10 within 2 h, and the dissolution rate and degree of CUR in artificial gastrointestinal fluid were significantly increased. Soluplus could effectively maintain the supersaturated state of CUR and enhance CUR dissolution in vitro.

Design, Preparation, and Characterization of Dioscin Nanosuspensions and Evaluation of Their Protective Effect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice.

The purpose of this study was to prepare a dioscin nanosuspension (Dio-NS) that has a better distance and high solubility for oral administration and to evaluate its hepatoprotective effects. Optimal primary manufacture parameters, including shear time, shear speed, emulation temperature, pressure, and cycles of homogenization, were determined by single-factor experiments. The concentrations of dioscin, SDS, and soybean lecithin were optimized using the central composite design-response surface method, and their effects on the mean particle size (MPS) and particle size distribution of Dio-NS were investigated. Characterization of the Dio-NS formulations included examinations of the surface morphology and physical status of dioscin in Dio-NS, the stability of Dio-NS at different temperatures, in vitro solubility, and liver protective effect in vivo. Under optimal conditions, Dio-NS had an MPS of 106.72 nm, polydispersity index of 0.221, and zeta potential of −34.27 mV. Furthermore, the proportion of dioscin in Dio-NS was approximately 21.26%. The observation of particles with a spherical shape and the disappearance of crystalline peaks indicated that the physical and chemical properties of Dio-NS were altered. Furthermore, we observed that the dissolution of Dio-NS was superior to that of a physical mixture and Dio-GZF. Moreover, Dio-NS was demonstrated to have a protective effect against CCl4-induced acute liver damage in mice that was equivalent to that of silymarin (a positive control drug) at the same dose. The good hepatoprotective effect of our Dio-NS preparation can provide a theoretical basis for investigating its absorption mechanisms in the body.

Optimization of formulation and preparation technology of lutein liposomes by central composite design-response surface method

Optimization of formulation and preparation technology of lutein liposomes by central composite design-response surface method

Preparation and Quality Evaluation of Salvianolic Acids and Tanshinones Dry Powder Inhalation

Salvianolic acids and tanshinones both exhibit efficacy in treating idiopathic pulmonary fibrosis (IPF), but their formulation limits their clinical use. This study aimed to prepare the salvianolic acids and tanshinones dry powder for inhalation (SPI) to achieve pulmonary delivery for the treatment of IPF. The variable quantities of salvianolic acids and tanshinones composite powder were optimized using the central composite design-response surface method. Different carriers with various drug-carrier ratios were optimized to prepare SPI. The final optimized formulation of SPI was as follows: InhaLac 230® was selected as the carrier with drug:carrier = 1:6, and the milled lactose InhaLac 400® was added at 5%. The developed SPI characterized with an angle of repose 52.46 ± 1.04°, Carr's index of 34.00 ± 0.50% and showed high lung deposition in vitro, indicating the potential of pulmonary delivery for the treatment of IPF.

Optimizatoin of extraction technology of compound purgative Moringa Oleifera based on central composite design and response surface method

Objective To optimize the extraction technology of Compound purgative Moringa Oleifera by central composite design-response surface method. Methods The content of isoquercetin and astragalin, the yield of dry extract and overall desirability (OD) were used as the evaluation indexes; the factors such as water addition, extraction times and time for extraction were employed to optimize extraction technology of central composite design-response surface method. Results Optimal extraction technology was as follows: 3 times extracted with 10-fold the amount of water for 1 h each time. Conclusions Central composite design-response surface method was suitable for optimizing extraction technology of compound purgative Moringa Oleifera. Key words: Extraction; Technology improving (TCD); Central composite design-response surface method; Compound purgative Moringa Oleifera

Preparation and antitumor effects of tanshinone ⅡA loaded albumin nanoparticles

In this study, the tanshinone ⅡA loaded albumin nanoparticles were prepared by high pressure homogenization method. The formulation was optimized by central composite design-response surface method (CCD-RSM), with the particle size, encapsulation efficiency, and drug loading as indexes to investigate their in vitro anti-tumor effect. The results showed that the prepared nanoparticles had uniformly spherical morphology and uniform particle size distribution. The average particle size, encapsulation efficiency and drug loading of nanoparticles were about (175.7± 3.07) nm, 90.8%±1.47% and 5.52%±0.09%, respectively. Tanshinone ⅡA loaded albumin nanoparticles showed a more powerful antitumor effect than free tanshinone ⅡA for human promyelocytic leukemia NB4 cells. The preparation method of the drug-loaded albumin nanoparticles was simple and easy, and can significantly improve the solubility of tanshinone ⅡA, so it was helpful to extend its application in therapies against hematological malignancies.

Response surface method for optimization of asiatic acid nanoparticles modified with PEG and its enhancing effects on intestinal absorption

A solvent diffusion method was used to prepare pegylated asiatic acid (AA) loaded nanostructured lipid carriers (p-AA-NLC). Then central composite design-response surface method was used to obtain optimum condition for preparation technology of p-AA-NLC, where PEG/lipid ratio was 8.0% and AA/lipid ratio was 22.0%. Under the optimum condition, the system had particle size of (111.2±2.9) nm, Zeta potential of (-37.1±0.9) mV, drug loading of (15.4±0.2)% and entrapment efficiency greater than 90%. The deviations between observed values and predicated values were all below 5%, indicating that the established model had a good predictability. Meanwhile, a low-speed single pass perfusion model of rat in situ was set up to estimate the absorption kinetics of p-AA-NLC in small intestine, where the effective permeability (Peff), absorption rate constant (Ka) and other parameters were used to evaluate the drug absorption. It turned out that Peff and Ka in p-AA-NLC group were significantly higher than those in unmodified group (P<0.05), indicating that asiatic acid loaded nanostructured lipid carriers (AA-NLC) could enhance the effects on intestinal absorption after being modified with hydrophilic PEG.

Application Research of Lipid Microsphere Biological Carrier Material on Prescription of Tanshinone II a Lipid Microsphere by Central Composite Design-Response Surface Method

To optimize the prescription of tanshinone IIA lipid microspheres by central composite design method, and evaluate the quality. Through evaluating average particle size, stability constant and the encapsulation efficiency of the lipid microsphere to investigate the concentration of the egg yolk lecithin and the poloxamer and the percentage of Soybean oil in the total oil phase which may impact the properties of tanshinone IIA lipid microsphere. Building the mathematic relation between the index and factor by the binomial expression, according to the best mathematical model of the evaluation indicators to describe response surface and then to use response surface method to predict the best prescription which will be analysed. According to the prescription optimization to prepare tanshinone IIA lipid microsphere and evaluate its quality. The results showed that each index of the binomial equation fitting is good, the correlation coefficient of the average particle size, stability constant and the encapsulation efficiency are 0.97, 0.92 and 0.84 respectively. The optimized prescription is as follows: egg yolk lecithin1.38 g, F68 0.19 g, LCT 2 g, MCT 18 g, all the indexes of the optimized prescription are similar to the target values.

Study on the Extraction of Polyphenol from Artocarpus Altilis with Ultrasonic Wave Technology Optimized by Central Composite Design-Response Surface Method

Response surface methodology (RSM) was used to optimize ultrasonic-assisted extraction for total polyphenols from Artocarpus altilis based on single-factor experiment. The main factors, ultrasonic time, the liquid-solid ratio, the extraction temperature, the type of addition acid of single factor experiment was surveyed; the principle of design for 2 factors (extraction time and liquid-solid ratio) 2 levels response surface methodology was applied and the response surface optimization extraction conditions were studied. The ultrasonic wave frequency of 37 kHz at 550W power, the ethanol concentration of 70o, the extracting temperature of 75oC, the extracting time of 35 minutes, and the ratio of solvent volume of 13.9:1 (Extracted 4 times) at pH 3.5 were selected as the optimum conditions, the extraction yield of polyphenols was 391.5862 mg/g (P < 0.05). Ultrasonic extraction is a good method for saving time, energy and material, and can be applied to the polyphenols extraction. This result revealed that potent of utilization low-value material to produce the polyphenol product at industrial scale.

Development of biphasic drug-loading lipid emulsion of Salvia miltiorrhiza and its quality evaluation

The feasibility of simultaneously loading both liposoluble and water-soluble components of Salvia miltiorrhiza in emulsion was discussed, in order to provide new ideas in comprehensive application of effective components in S. miltiorrhiza in terms of technology of pharmaceutics. With tanshinone II (A) and salvianolic acid B as raw materials, soybean phospholipid and poloxamer 188 as emulsifiers, and glycerin as isoosmotic regulator, the central composite design-response surface method was employed to optimize the prescription. The coarse emulsion was prepared with the high-speed shearing method and then homogenized in the high pressure homogenizer. The biphasic drug-loading intravenous emulsion was prepared to investigate its pharmaceutical properties and stability. The prepared emulsion is orange-yellow, with the average diameter of 241 nm and Zeta potential of -35.3 mV. Specifically, the drug loading capacity of tanshinone II (A) and salvianolic acid B were 0.5 g x L(-1) and 1 g x L(-1), respectively, with a good stability among long-term retention samples. According to the results, the prepared emulsion could load liposoluble tanshinone II (A) and water-soluble salvianolic acid B simultaneously, which lays a pharmaceutical foundation for giving full play to the efficacy of S. miltiorrhiza.

TPGS-g-PLGA/Pluronic F68 mixed micelles for tanshinone IIA delivery in cancer therapy

Tanshinone IIA (TAN) has few clinical applications for anti-cancer therapy mainly due to its high lipophicity, low cellular uptake, and poor bioavailability. To improve the anti-cancer effect and bioavailability of TAN, we developed a mixed micelle system constituted with d-α-tocopheryl polyethylene glycol succinate-graft-poly(d,l-lactide-co-glycolide) (TPGS-g-PLGA) copolymer and Pluronic F68. TAN was encapsulated in the TPGS-g-PLGA/Pluronic F68 mixed micelles by using the thin film hydration technology optimized by the central composite design/response surface method (CCD/RSM). TAN-loaded mixed micelles were highly stable in the presence or absence of bovine serum albumin (BSA) and achieved sustained drug release in vitro. Compared with free TAN, TAN mixed micelles had higher cytotoxicity and pro-apoptotic effects against human hepatocellular carcinoma HepG2 cells. The significant enhancement on pro-apoptosis by TAN micelles was evidenced by increased chromosome condensation, mitochondria membrane potential loss, cell apoptosis, and cleavages of caspase-3 and PARP. Furthermore, pharmacokinetic studies revealed that TAN mixed micelles significantly prolonged the circulation time and improved bioavailability of TAN in rats. These results demonstrated that TAN-loaded TPGS-g-PLGA/F68 mixed micelles are an effective strategy to deliver TAN for cancer therapy.

The 32.5% difenoconazole-azoxystrobin effervescent tablet optimized by central composite design-response surface method

The aims of the present study are to exam the dispersing agent,disintegrating agent and blowing agent,based on the index of tablet suspension rate and disintegration time.The data is simulated by using multi-nolinear equation to select proper model.The best formulations based on the factors within setting ranges are: WG5(4.75%),TXC(1.50%),PVPP(5.00%),foaming agent(40%).Three times of repeated experiments showed that the average rate of suspension was 86.42%,disintegration time was 159 s,almost equal to the predictions: 86.14% and 160 s.

Optimized Extraction Technology for Chlorogenic Acid from Sweet Potato Leaf by CCD/RSM

The aim of this study was to optimized extraction chlorogenic acid from sweet potato leave by central composite design/response surface method (CCD/RSM). The effects of ethanol concentration, ratio of solid to liquid, and extraction time on the yield of chlorogenic acid were evaluated, and the yield of chlorogenic acid under analysis optimum condition was also forecasted. The optimized extraction conditions were as follows: extraction with a 20 fold volume of 70% aqueous ethanol solution for 2h. Under these conditions the theoretical yield of chlorogenic acid was 15.95 mg/g, and the measured value was 15.89 mg/g. This method is scientific, reasonable and feasible. It also laid a foundation for research and application of chlorogenic acid in sweet potato leaves.