Integrating Artificial Intelligence with Quality by Design in the Formulation of Lecithin/Chitosan Nanoparticles of a Poorly Water-Soluble Drug.

The aim of the current study is to explore the potential of artificial intelligence (AI) when integrated with Quality by Design (QbD) approach in the formulation of a poorly water-soluble drug, for its potential use in carcinoma. Silymarin is used as a model drug for its potential effectiveness in liver cancer. A detailed QbD approach was applied. The effect of the critical process parameters was studied on each of the particle size, size distribution, and entrapment efficiency. Response surface designs were applied in the screening and optimization of lecithin/chitosan nanoparticles, to obtain an optimized formula. The release rate was tested, where artificial neural network models were used to predict the % release of the drug from the optimized formula at different time intervals. The optimized formula was tested for its cytotoxicity. A design space was established, with an optimized formula having a molar ratio of 18.33:1 lecithin:chitosan and 38.35 mg silymarin. This resulted in nanoparticles with a size of 161 nm, a polydispersity index of 0.2, and an entrapment efficiency of 97%. The optimized formula showed a zeta potential of +38 mV, with well-developed spherical particles. AI successfully showed high prediction ability of the drug's release rate. The optimized formula showed an enhancement in the cytotoxic effect of silymarin with a decreased IC50 compared to standard silymarin. Lecithin/chitosan nanoparticles were successfully formulated, with deep process and product understanding. Several tools were used as AI which could shift pharmaceutical formulations from experience-dependent studies to data-driven methodologies in the future.

Quality by Design as a Tool in the Optimisation of Nanoparticle Preparation-A Case Study of PLGA Nanoparticles.

Nanoparticles can be used as drug carriers in various applications (e.g., in pulmonary drug delivery and mucosal vaccination). For further investigations, such as drug release studies, as well as for cell and tissue targeting, particles with defined properties are needed. The purpose of the study was to show a multi-step systematic method utilising quality by design to ensure the quality of ovalbumin loaded polylactic-co-glycolic acid nanoparticles (OVA-PLGA-NP), which can be delivered to the lung, and to gain knowledge of the preparation method (double-emulsion solvent evaporation method) in an early development process. Within a definitive screening design, several process parameters (OVA, PLGA and stabiliser concentrations, stirring time and stirring speed of inner emulsion and stirring time and stirring speed of double emulsion) were varied to analyse their impact on resulting properties (z-average, PDI, loading efficiency and loading capacity). The results showed that the preparation of the inner emulsion mainly influenced the drug loading, while the parameters of the second emulsifying step controlled the size. Then a central composite response surface design was used to achieve a predictable OVA-PLGA-NP with an average particle size of 700 nm and high drug-loading. This also enabled the demonstration of curvature and interaction of the stabiliser and the PLGA concentration.

Optimization of the Extraction Process and Antioxidant Activity of Polysaccharide Extracted from Centipeda minima.

The purpose of this study is to optimize the extraction process and study antioxidant activity of Polysaccharide extracted from Centipeda minima. The Box-Behnken design-response surface methodology was adopted to optimize the extraction process of polysaccharides from Centipeda minima. We purified the crude polysaccharides from Centipeda minima, as well as determined the purity, monosaccharide composition, and molecular weight of the purified fraction. Fourier transform infrared spectrometer (FT-IR) and scanning electron microscopy (SEM) were used to analyze the structural features of the polysaccharides. Further, we investigated the antioxidant activities of different fractions of polysaccharides. Consequently, the results showed that the optimum extraction conditions for polysaccharides were: a liquid-solid ratio of 26 mL/g, extraction temperature of 85.5 °C, and extraction time of 2.4 h. Moreover, the yield of polysaccharides measured under these conditions was close to the predicted value. After purification, we obtained four components of Centipeda minima polysaccharides (CMP). The purity, monosaccharide composition, molecular weight, and structural characteristics of CMP were different, but with similar infrared absorption spectra. CMP exhibited a typical infrared absorption characteristic of a polysaccharide. Besides, CMP displayed good antioxidant activity, with potential to scavenge DPPH radical, hydroxyl radical, and superoxide radical. Therefore, this study provides a reference for future research on the structure and biological activity of CMP, and lays a theoretical foundation for food processing and medicinal development of CMP.

Optimization of molding process and physical fingerprint of Shuangye pipa granules based on QbD concept / 中国药房

OBJECTIVE To optimize the molding process of Shuangye pipa granules based on the concept of quality by design （QbD） and analyze its physical fingerprint. METHODS The dry extract of Shuangye pipa granules was used as the main drug. The retention rate of total flavonoid， moisture absorption rate， dissolution rate， angle of repose and molding rate of the granules were selected as evaluation indexes. The single-factor test combined with the entropy weight method and Box-Behnken response surface design was used to optimize the molding process， and validation test was conducted. The physical fingerprints of 10 batches of Shuangye pipa granules prepared by the optimal process were comprehensively analyzed by eight secondary physical indexes （relative homogeneity， moisture， moisture absorption rate， Hausner ratio， angle of repose， bulk density， tap density and porosity）. RESULTS The optimal molding process of Shuangye pipa granules was as follows： soluble starch-maltodextrin-mannitol was 1∶1∶1 （m/m/m）， 95% ethanol was as wetting agent and the amount of it was 37%， the drug-assisted ratio was 1∶0.8 （m/m）， the drying temperature was 59 ℃， drying time was 28 min. The results of 3 validation tests showed that the average comprehensive score was 0.879 6， the RSD of which with prediction value （0.881 9 score） was 1.97%. The similarity between the physical fingerprints of 10 batches of Shuangye pipa granules and the control physical fingerprint was higher than 0.99. CONCLUSIONS The optimized molding process of Shuangye pipa granules is stable and feasible， and the physical property of Shuangye pipa granules is stable and controllable.

Colon Targeted Eudragit Coated Beads Loaded with Optimized Fluvastatin-Scorpion Venom Conjugate as a Potential Approach for Colon Cancer Therapy: In Vitro Anticancer Activity and In Vivo Colon Imaging.

Preclinical studies suggest that most of statins or 3­hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors possess pleiotropic anticancer activity. The aim of the present work was to investigate the conjugation of the statin fluvastatin (FLV) with scorpion venom (SV), a natural peptide with proven anticancer properties, to enhance FLV cytotoxic activity and prepare colon targeted FLV-SV nanoconjugate beads for management of colon cancer. Response surface design was applied for the optimization of FLV-SV nanoconjugates. FLV-SV particle size and zeta potential were selected as responses. Cytotoxicity of optimized FLV-SV nanoconjugates was carried out on Caco2 cell line. Colon targeted alginate coated Eudragit S100 (ES100) beads for the optimized formula were prepared with the utilization of barium sulfate (BaSO4) as radiopaque contrast substance. Results revealed that optimized FLV-SV nanoconjugates showed a size of 71.21 nm, while the zeta potential was equal to 29.13 mV. Caco2 cells were considerably more sensitive to the FLV-SV formula (half-maximal inhibitory concentration (IC50) = 11.91 µg/mL) compared to SV and FLV used individually, as shown by values of IC50 equal to 30.23 µg/mL and 47.68 µg/mL, respectively. In vivo imaging of colon targeted beads, carried out by employing real-time X-ray radiography, confirmed the efficiency of colon targeted beads. Overall our results indicate that the optimized FLV-SV nanoconjugate loaded alginate coated ES100 beads could represent a promising approach for colon cancer with efficient colon targeting ability.

Rapid and easy ICP OES determination of selected major, minor and trace elements in Pu-erh tea infusions using the response surface methodology along with the joint desirability function approach.

A new analytical method was proposed for multielement (Al, Ba, Ca, Cu, Fe, K, Mg, Mn, Na, Sr and Zn) analysis of Pu-erh teas infusions by inductively coupled plasma optical emission spectrometry. The Box-Behnken response surface design together with individual desirability functions and the joint desirability function approach was applied to develop experimental conditions of this new procedure, being alternative to high-temperature wet digestion. The procedure involved the samples to be just 5-fold diluted with 1.7 mol L-1 HNO3. The proposed method was precise (relative standard deviations within 2-8%), true (relative errors from -8 to +6%) and guaranteed very good detectability (detection limits within 1-6 ng g-1, except for Ca and Fe). It was used for analysis of infusions of Pu-erh teas as well as to verify the effect of their preparation conditions (steeping water temperature, steeping time).

Real-Time Sensing of Output Polymer Flow Temperature and Volumetric Flowrate in Fused Filament Fabrication Process.

In this paper we addressed key challenges in engineering an instrumentation system for sensing and signal processing for real-time estimation of two main process variables in the Fused-Filament-Fabrication process: (i) temperature of the polymer melt exiting the nozzle using a thermocouple; and (ii) polymer flowrate using extrusion width measurements in real-time, in-situ, using a microscope camera. We used a design of experiments approach to develop response surface models for two materials that enable accurate estimation of the polymer exit temperature as a function of polymer flowrate and liquefier temperature with a fit of R2=99.96% and 99.39%. The live video stream of the deposition process was used to compute the flowrate based on a road geometry model. Specifically, a robust extrusion width recognizer REXR algorithm was developed to identify edges of the deposited road and for real-time computation of extrusion width, which was found to be robust to filament colors and materials. The extrusion width measurement was found to be within 0.08 mm of caliper measurements with an R2 value of 99.91% and was found to closely track the requested flowrate from the slicer. This opens new avenues for advancing the engineering science for process monitoring and control of FFF.

Finding the right mix: a framework for selecting seeding rates for cover crop mixtures.

Cover crop mixtures have the potential to provide more ecosystem services than cover crop monocultures. However, seeding rates that are typically recommended (i.e. seeding rate of monoculture divided by the number of species in the mixture) are non-optimized and often result in the competitive species dominating the mixture, and therefore limiting the amount of ecosystem services that are provided. We created an analytical framework for selecting seeding rates for cover crop mixtures that maximize multifunctionality while minimizing seed costs. The framework was developed using data from a field experiment, which included six response surface designs of two-species mixtures, as well as a factorial replacement design of three-species and four-species mixtures. We quantified intraspecific and interspecific competition among two grasses and two legume cover crop species with grass and legume representing two functional groups: pearl millet [Pennisetum glaucum (L.) R.Br.], sorghum sudangrass [Sorghum bicolor (L.) Moench × Sorghum sudanense (Piper) Stapf], sunn hemp (Crotalaria juncea L.), and cowpea [Vigna unguiculata (L.) Walp]. Yield-density models were fit to estimate intraspecific and interspecific competition coefficients for each species in biculture. The hierarchy from most to least competitive was sorghum sudangrass > sunn hemp > pearl millet > cowpea. Intraspecific competition of a less competitive species was the greatest when the biculture was composed of two species in the same functional group. Competition coefficients were used to build models that estimated the biomass of each cover crop species in three-species and four-species mixtures. The competition coefficients and models were validated with an additional nine site-years testing the same cover crop mixtures. The biomass of a species in a site-year was accurately predicted 69% of the time (low root mean square error, correlation > 0.5, not biased, r2 > 0.5). Applying the framework, we designed three-species and four-species mixtures by identifying relative seeding rates that produced high biomass with high species evenness (i.e. high multifunctionality) at low seed costs based on a Pareto front analysis of 10,418 mixtures. Accounting for competition when constructing cover crop mixtures can improve the ecosystem services provided, and such an advancement is likely to lead to greater farmer adoption.

Construction of a Tl(I) voltammetric sensor based on ZIF-67 nanocrystals: optimization of operational conditions via response surface design.

An electroanalytical sensor was constructed constituted on a carbon paste electrode (CPE) with a ZIF-67 modifier and devoted to the quantification of Tl(I). Several characterization tests including XRD, BET, FT-IR, SEM/EDS/mapping, TEM, impedance spectroscopy (EIS), and cyclic voltammetry (CV) were performed on the synthesized ZIF-67 nanocrystals and CPE matrix. Central composite design (CCD) was used to assess the impact of variables affecting the sensor response, including the weight percent of ZIF-67 (14%), the pH of the thallium accumulation solution (6.4), and accumulation time (315 s) as well as the accumulation potential (-1.2 V). The direct linear relationship between the sensor response and the concentration of Tl(I) is in the interval of 1.0×10-10 to 5.0×10-7 M (coefficient of determination = 0.9994). The detection limit is approximately 1.0 × 10-11 M. The right selection of the MOF makes this sensor highly resistant to the interference of other ions. High selectivity against common interferences in the measurement of thallium (such as Pb(II) and Cd(II)) is an important feature of this sensor. To confirm the performance of the prepared sensor, the amount of thallium in the real sample was determined.

Comparative Study of the Influence of Bio-Resin Color on the Dimension, Flatness and Straightness of the Part in the 3D Printing Process.

This paper aims to determine whether the color of based-plant resin called, by the manufacturer, eco-resin has an influence on the dimensions and geometric accuracy of the 3D-printed part. The analysis of flatness, straightness and dimensions deviations was carried out with high-precision measurement systems, and according to current standards regarding linear dimensions and geometrical tolerances. A coordinate measuring machine with contact probes was used to measure the printed part's physical characteristics, and analysis of variance and response surface design methods were used for the data analysis. The printing experiment was carried out for each color. After that, the measurement of the printed parts and the study of the data were performed. The first finding is that for black and clear eco-resin, there are problems with the printing of the supports. Based on standard data for the range of nominal lengths of the part for linear dimensions, flatness and straightness, the measurement results can be included in different tolerance classes within standard value limits. The best value of the printed structure was obtained for clear eco-resin. The paper demonstrates that the impact of the color of the eco-resin is more important than the supports density for all the studied features. Based on 3D measurements, the optimal values for each of the eco-resin colors regarding the flatness, straightness and linear dimensions deviations of the 3D printed part were also determined.

Preparation and characterization of 96-well microplates coated with molecularly imprinted polymer for determination and biosimilarity assessment of recombinant human erythropoietin.

Synthesis and applications of molecularly imprinted polymers (MIP) are rapidly growing. In this study, a biomimetic MIP was prepared through silanes polymerization on the surface of 96-well microplates using recombinant human erythropoietin-alfa (rhEPO) as a template molecule. The rhEPO was immobilized onto the plate surface using bi-functional cross-linker and a thin imprinted layer following sol-gel procedure was constructed. After template extraction, uniform three-dimensional cavities compatible with the configuration of rhEPO were obtained. The rhEPO-MIP preparation was optimized using 2-level factorial design and response surface design where polymerization time and interactions between the different variable were found to be the most significant factors. Size-exclusion chromatography (SEC) was used to monitor the stability of the rhEPO under the investigated polymerization conditions. Determination of rhEPO using the MIP microplate showed good dynamic response fitting to the 4 PL regression model (0.9962) over a concentration range of 10.00 - 100.00 ng mL-1. Adsorption of rhEPO onto MIP followed the Langmuir isotherm model (r = 0.9957, χ2 =0.02786) with pseudo-second-order kinetics (r = 0.9984). The surface of the rhEPO-MIP was characterized using scanning electron microscopy (SEM) while step-by-step surface modification was tracked using Fourier transform infrared (FTIR) spectroscopy. The rhEPO-MIP was able to distinguish between the rhEPO-alfa template and modified rhEPO molecules; rhEPO-beta, hyperglycosylated and pegylated forms (imprinting factors < 2) and in the commonly used formulation additive human serum albumin (HSA) (R% = 113.96 -95.22%). The rhEPO-MIP was applied to compare the receptor-binding pattern to rhEPO and its biosimilars / structural analogues. The results were cross-validated using the conventional assay protocol (RP-HPLC and ELISA) and an acceptable correlation was observed with RP-HPLC (maximum deviation is 7.78%). This work confirmed the applicability of rhEPO-MIP with its unique binding features for batch release, stability and biosimilarity assessment as well as subsequent evaluation of batch-to-batch consistency during bioproduction of target analytes.

A Quality by Design Approach of Metronidazole Bigel and Assessment of Antimicrobial Study Utilizing Box-behnken Design.

OBJECTIVE: The present investigation aimed to prepare metronidazole (MTZ) topical bigel for the effective delivery of MTZ and to study the effect of applied variables as per statistical design. The study also signifies the implementation of the statistical method using the Quality by Design technique for MTZ bigel. METHODS: The MTZ bigels were prepared as per the runs suggested by Box Behnken design (BBD) using statistical software. A total of 28 runs were suggested by the BBD, considering sodium carboxymethylcellulose (Na CMC), guar gum, hydrogel and RPM as independent variables. The prepared bigels were evaluated for organoleptic properties, percentage drug content, spreadability, viscosity, percentage in-vitro drug release, and antimicrobial efficacy. Model selectivity was ascertained by p-value considering responses along with predicted R2 and adjusted R2 values.The fitting of model was ascertained by F-value as well as "lack of fit" was carried out to find out the suitability of the experimental design. Furthermore, the characteristic distribution of data was ascertained by the "normal plot of residual" method. The compatibility of MTZ and excipients in bigels was confirmed by FTIR and the crystalline nature of MTZ in formulations was studied by DSC and XRD studies. Furthermore, the dispersion of bigel was assessed by the SEM study. RESULTS: The effect of independent variables on spreadability (mm), viscosity (cp), pH, drug release in 6 hours (%)and drug content (%) was evaluated. The optimized formulation was selected and evaluated by a polynomial equation while considering the p-value. These variables showed a significant effect on responses. A less significant difference was observed (6.37, 14463, 6.97, 86.29, and 67.47, respectively, for spreadability, viscosity, pH, and percentage drug release and % drug content) between the observed and predicted values indicating the model's suitability. The prepared bigels were found to be compatible and globules uniformly dispersed throughout the bigel. CONCLUSION: The 3D response surface design ascertained the optimal MTZ bigel at 1.25g of NaCMC, 0.5g of guargum, 37.5g hydrogel, and 1000 RPM. The selected bigel showed good antimicrobial efficacy against S. Aureus and may be considered an effective delivery vehicle for MTZ.

Statistical Design of Sustained-Release Tablet Garcinia cambogia Extract and Bioconverted Mulberry Leaf Extract for Anti-Obesity.

Obesity is a major health concern worldwide, and it is leading to worsening disease morbidity and mortality. Herbal supplements and diet-based therapies have attracted interest in the treatment of obesity. It is known that Garcinia cambogia (GA) and mulberry leaf, which contain polyphenols, have anti-obesity activity. Herein, we developed a combined tablet consisting of GA extract and bioconverted mulberry leaf extract (BMUL) using a statistical design approach. The ratio and amount of sustained polymers were set as factors. In the cell study, the combination of GA and BMUL showed synergistic anti-obesity activity. In a statistical model, the optimized amounts of hydroxypropyl methylcellulose 2208 (HPMC 2208) and polyethylene oxide 303 (POLYOX 303) were 41.02% and 58.98%, respectively. Additionally, the selected ratio of microcrystalline cellulose (MCC) was 0.33. When the release, hardness, and friability of the GABMUL tablet were evaluated, the error percentages of the response were lower than 10%. This indicates that the GABMUL tablet was successfully prepared.

Species Identity and Initial Size Rather Than Neighborhood Interactions Influence Survival in a Response-Surface Examination of Competition.

To measure intraspecific and interspecific interaction coefficients among tree species is the key to explore the underlying mechanisms for species coexistence and biodiversity maintenance in forests. Through the response surface experimental design, we established a long-term field experiment by planting 27,300 seedlings of four tree species (Erythrophleum fordii, Pinus massoniana, Castanopsis fissa, and Castanopsis carlesii) in 504 plots in different species combinations (six pairwise combinations of four species), abundance proportions (five abundance proportions of two species, i.e. A: B = 1:0, 3:1, 1:1, 1:3, 0:1), and stand densities (25, 36, 64, and 100 seedlings per plot). In this initial report, we aimed to quantify the relative importance of biotic and abiotic factors on seedling survival at the early stage of growth, which is a critical period for seedling establishment. We found that plot-level seedling survival rate was determined by species combination and their abundance proportion rather than stand density. At the individual level, individual survival probability was mainly explained by species identity, initial seedling size, and soil conditions rather than neighborhood competition. Our study highlights that the seedling intrinsic properties may be the key factors in determining seedling survival rate, while neighborhood effects were not yet prominent at the seedling life stage.

Waste-to-resources: Green preparation of magnetic biogas residues-based biochar for effective heavy metal removals.

The agricultural wastes disposal and polluted water purification are always the key issues of environmental restoration. In this work, a magnetic biogas residue-based biochar (mBR-C) by direct pyrolysis and sonochemical method was prepared from biogas residue (BR). Response design methodology based on Box-Behnken design was used for the preparation parameters optimization. The characterization results identified that mBR-C had well-developed pore structure and surface area, which was beneficial to diffuse and capture heavy metal ions. Traces of toxic heavy metal in mBR-C was leached (˂0.04 mg/L) through TCLP method, indicating the environmental safety of the magnetic biochar. Meanwhile, the mBR-C exhibited excellent solid-liquid separation efficiency because of its strong magnetism. The series of adsorption experiments indicated that mBR-C could capture Cu2+ and Pb2+ rapidly, and the maximum adsorption capacity for Cu2+ and Pb2+ was 75.76 and 181.82 mg/g, respectively, which was higher than some other biochars previously reported. mBR-C was further applied in the synthetic wastewater treatment, which could effectively purify at least 600 mL (150 BV) to meet emission standards. After several column adsorption-desorption cycles, the adsorption capacity could still reach 85%, implying that mBR-C has good reusability and stability. Overall, the mBR-C can be used as an eco-friendly, desirable, economic and recyclable biosorbent in heavy metal polluted water treatment, providing a new idea for a combination of biogas residue recycle and wastewater treatment.

Removal of sulfamethoxazole, sulfadiazine, and sulfamethazine by UV radiation and HO• and SO4•- radicals using a response surface model and DFT calculations.

In this work, the degradation of sulfamethazine (SMT), sulfadiazine (SMD), and sulfamethoxazole (SMX) by using UV light, UV/H2O2, and UV/S2O8-2 was analyzed. Direct photolysis was studied by varying the lamp power and the solution pH. DFT calculations were carried out to corroborate the efficiency of the degradation as a function of the solution pH. The variation of the apparent rate constant, kap, was determined in the indirect photolysis by employing an experimental Box-Behnken-type response surface design. The results evidenced that SMX can be efficiently degraded by applying UV radiation independent of the operating conditions. Nevertheless, the quantum yields for SMT and SMD were close to zero, indicating a low energy efficiency for their photochemical transformation. The effect of the solution pH showed that the photodegradation of sulfonamides depends both on the amount of radiation absorbed as the electronic density. Calculations based on density functional theory and supported by the quantum theory of atoms in molecules allowed to describe fragmentation patterns in the systems under study, proving the lability of S14-C2, N17-C18, and N22-O22 bonds, for SMT, SMD, and SMX, respectively. From response surface methodology, four statistically reliable equations were obtained to determine the kap value as a function of the system operating conditions. Finally, SO4•- radicals proved to have a higher reactivity to degrade SMT and SMD compared with HO• radicals regardless of the operating conditions of the system.

Towards green analysis of curcumin from tea, honey and spices: Extraction by deep eutectic solvent assisted emulsification liquid-liquid microextraction method based on response surface design.

A fast, cheap and green analytical method was developed for the determination and extraction of curcumin in tea, honey, and spices using deep eutectic solvent-assisted emulsification liquid-liquid micro-extraction (DES-ELLME) coupled to UV-VIS spectrophotometry. Quantitative extraction of curcumin from the sample was obtained by the DES, which was prepared by mixing choline chloride and maltose in a 1:3 molar ratio. Response surface design was used for the optimisation of significant experimental parameters including sample pH, amount of extraction solvent, amount of emulsifier solvent and vortex time. The optimum conditions obtained were pH 4.25, 762.5 µL of DES, 107.5 mL of tetrahydrofuran and 3.4 min vortex time, while keeping centrifugation speed fixed at 4000 rpm, 5 min. Under the extraction conditions obtained, analytical features such as calibration equation, limit of detection, enrichment factor, and linearity were Abs = 6.5 × 10-4 [Curcumin, ng mL-1]-1.2 × 10-5, 0.1 ng mL-1, 114 and 0.4-120 ng mL-1, respectively. Moreover, the repeatability and reproducibility of the DES-ELLME method, expressed as relative standard deviation (RSDs%), varied in the ranges of 1.4-3.0% and 2.0-4.3%, respectively. Finally, the proposed method was successfully applied to the extraction and determination of curcumin from prepared samples. The relative mean recovery ranged from 92.3% to 104.4%.

Optimization of a solid-phase microextraction technique for chloro­ and nitro- substituted aromatic compounds using design of experiments.

A rapid and sensitive direct immersion solid-phase microextraction (SPME) technique for the analysis of seven chloro (Cl-) and nitro (NO2-) substituted anilines, toluenes, and nitrobenzenes from small volume (1.5 mL) aqueous samples was optimized for gas chromatography using Design of Experiments (DoE). Screening of the SPME factors was performed by a fractional factorial DoE, and the optimization of influential factors was achieved with a central composite multi-response surface DoE. Extraction time, pre-SPME agitation speed, extraction temperature, and desorption temperature were identified as significant factors and their values were set using a desirability function that maximized the extraction of the seven target analytes. Extraction time and agitation speed showed significant interactions for most analytes (α = 0.05). The relative standard deviations (RSDs) for within-day and between-day analyses were below 8%, suggesting that the method was repeatable and reproducible. The obtained limits of detection were in the low µg/L range (1-10) using a Flame Ionization Detector, far below what is needed for industrial contaminated sites (usually >1 mg/L). The optimized SPME method increased the analyte concentration up to 2-3 orders of magnitude compared with direct GC injection. The optimized SPME method was applied to two groundwater samples from a contaminated site in which the concentrations of three of the target analytes were ranged from 0.06 to 9.42 mg/L with RSDs <11%. When the concentrations of the target analytes in the sample matrix were higher than 0.5 mg/L, a competition for the SPME extraction sites was observed where analytes with higher affinity for the fiber material replaced the analytes with lower affinity. As a result, dilution of highly contaminated samples is recommended. This study provided for the first time an analytical method for the quantification of frequently co-occurring contaminants from the chloro­ and nitro- substituted aniline, toluene, and nitrobenzene families.

Optimization of extraction technology of poly-mannuronic acid to a green delivery system for the water-insoluble pesticide, λ-Cyhalothrin.

Poly-mannuronic acids (PMs) have been considered as great biodegradable polymers as a green carrier for the potential pesticide deliver. In this work, the response surface design and microwave-assisted degradation were employed to obtain the optimum extraction conditions (i.e., 81 °C, 4.1 h, acid concentration 17.65 g/L). Meanwhile, the Ugi multi-component reaction makes the PM to be amphiphilic, called Ugi-PM, which induces the aggregation in aqueous solution at the concentration of 0.0895 g/L. The corresponding chemical structure and thermal stability of PM and Ugi-PM were determined by the FTIR, 1H NMR and thermogravimetric analysis (TG). Furthermore, the construction of novel emulsion-based delivery system using synthetic Ugi-PM was explored to prepare the pesticide of λ-Cyhalothrin. Interestingly, with the Ugi-PM concentration at 0.5 wt%, the stability of the Ugi-PM emulsion and the sustainable release of λ-Cyhalothrin are better than other concentrations and our previous system without degradation (Ugi-Alg emulsion). It is possible that electrostatic repulsion and steric hindrance derived from the hydrophobic Ugi-PM can promote the stability and flexible structure may be the reason for excellent sustained release of Ugi-PM emulsions in the pesticide deliver. The above-mentioned preparation progress is an efficient way to provide a valuable pesticide formulation.

Development of modified airlift reactor (MALR) for improving oxygen transfer: optimize design and operation condition using 'design of experiment' methodology.

Oxygen scarcity may significantly affect the process performance since it has low aqueous solubility and high demand by chemical and biological processes. The oxygen mass transfer is therefore necessary to enhance. This work aimed to develop the gas-liquid reactor, named Modified Airlift Reactor (MALR) for improving the oxygen transfer efficiency in terms of internal configurations and aeration parameters by equipping a vertical baffle for creating liquid circulation phenomena, and installing slanted baffles in the reactor riser to extend air-bubbles retention time and to improve their distributions. Since extremum conditions of the investigated factors may inefficient, optimum levels are required to identify. 2 k factorial and response surface design of Design of Experiment (DOE) methodology were applied to optimize these complex variables in terms of overall liquid mass transfer coefficient (K L a) of clean water. As a result, the main effective factors of MALR with their optimum value are amount of baffles (N b ∼ 3 baffles), baffle angle (α ∼ 50°), position of base area (Y r ∼ 10 cm), open space on baffle (A s ∼ 90 cm2), and gas flow (Qg). Increasing Qg resulted better K L a for the studied ranges (2-18 LPM). At the optimum condition, the improvement of MALR in terms of K L a coefficient was increased up to 97% and 28% compared to the regular bubble column and airlift reactor, respectively, at a certain gas flow without any extra energy. The correlation models of K L a coefficient with significant variables and power consumption were constructed for future estimation purposes.