Two-level Full Factorial Design Research Articles

Quality-by-design optimized RP-HPLC approach for the therapeutic drug monitoring of glibenclamide and fluoxetine in human plasma

Glibenclamide (GLB) and fluoxetine (FLX) were reported to have a potential drug-drug interaction when clinically co-administered. FLX is an inhibitor of CYP2C9 (the enzyme responsible for the metabolism of GLB), thus resulting in increased serum levels of GLB followed by severe hypoglycemia. Therefore, a sensitive, simple, and selective HPLC method is urgently needed for their simultaneous determination in plasma to be utilized for monitoring their therapeutic blood concentration levels. The current study introduces the first RP-HPLC approach for the simultaneous estimation of this binary mixture in less than 7 min. Adopting a quality-by-design (QbD) approach allowed for the designed approach to be optimized. Using a two-level full factorial design (25), the effects of various variables on the chromatographic responses were investigated and optimized. Hypersil BDS C18 column was used for the achievement of the optimum chromatographic separation at 19.9 °C using acetonitrile: sodium dihydrogen phosphate buffer (7.5 mM; pH 4, 60:40 % v/v) as a mobile phase, pumped isocratically at a flow rate of 1.036 mL/min. An injection volume of 30.0 μL was used for the binary mixture with UV detection at 230 nm. FLX and GLB calibration curves revealed an excellent linearity over the ranges of 0.025–10.00 and 0.02–10.00 µg/mL with limits of quantitation of 0.018 and 0.02 µg/mL, respectively. Due to the high sensitivity and selectivity, the method was successfully applied to the assay of the two drugs in spiked human plasma samples with reasonable % recoveries (92.70–108.50 %), indicating good bioanalytical applicability. Therefore, this study could be applied for the therapeutic drug monitoring of GLB and FLX in human plasma to control their potential drug-drug interaction. The suggested approach was also applied to estimate the investigated drugs in their dosage forms with reasonable % recoveries (96.80–102.80 %) and small % RSD values (less than 2 %). The method's excellent greenness was evaluated using three metric tools, including Analytical Eco-Scale, Green Analytical Procedure Index (GAPI), and Analytical Greenness (AGREE). Validation of the proposed method was performed according to ICH and US FDA guidelines.

Quantitative analysis of organosulphur compounds in crude oil samples using magnetic solid phase extraction based on Au-Fe3O4 adsorbent and gas chromatography with time-of-flight mass spectrometry

AbstractThis study focused on the development of a magnetic solid phase extraction (m-SPE) method using Au-Fe3O4 as an adsorbent followed by GC-ToFMS analysis for the determination of organosulphur compounds (OSCs) in fuel samples. The m-SPE using Au-Fe3O4 NPs was preferred because of the low toxicity of the adsorbent1, high separation efficiency using external magnet2 and greater extraction selectivity between sulphur and Au atom3. The Au-Fe3O4 NPs were characterized using XRD, UV–Vis, TEM, SEM and FTIR. This method was optimized using multivariate analysis based on a two-level full factorial and central composite designs. The conditions which produced optimum efficiency were found to be 150 mg mass of sorbent, 100 µL eluent volume, 50 min extraction time and 6,5 pH of the sample. These optimum conditions showed a relatively low limit of detection in the range of 0.02–0.199nµg/g and limit of quantification of 0.08–0.602 µg/g. Furthermore, a relative standard deviation of triplicates analysis was between 0.8 and 2.3% with good linearity of 0.9816–0.9961. The percentage recovery for thiophene, 3-methylthiophene, benzothiophene and dibenzothiophene ranged from 76 to 95% for the spiked samples. The optimized m-SPE method was then applied in real fuel oil samples. The concentration of thiophene, 3-methylthiophene, benzothiophene and dibenzothiophene in crude oil, gasoline, diesel and kerosene ranged from 0.43–1.94 µg/g, 0.78–1.63 µg/g, 0.95–4.31 µg/g to 1.55–2.09 µg/g, respectively. The m-SPE, followed by GC-ToFMS method, proved to be efficient, inexpensive and an alternative method for OSCs analysis in fuel oils.

Microemulsions and Nanoemulsions for Topical Delivery of Tripeptide-3: From Design of Experiment to Anti-Sebum Efficacy on Facial Skin.

The targeted delivery of a hydrophilic Tripeptide-3 to the skin using microemulsions or nanoemulsions for facial oil reduction was the focus of this study. The impact factors affecting oil/water transparent dispersion formation, such as the surfactant system, HLB value, and co-solvent, were identified through the water titration method and pseudoternary phase diagram plots. The interfacial tension between caprylic/capric triglyceride (CCT oil) and water was significantly reduced by the surfactant/co-surfactant combination (Smix) of Cremophore® RH40 and a double-tails co-surfactant, polyglycerol-3-diisostearate, at an HLB of 13 together with a water-to-co-solvent (PG) ratio of 1:1. A two-level full factorial design of experiment (FFD-DoE) emphasized the independent variables of the HLB value, co-solvent, and CCT oil contents affecting the optimal compositions for micro- or nanoemulsion formation. The low-energy spontaneous emulsification of the optimized combination at a low Smix content (10%) yielded the translucent oil-in-water Tripeptide-3 nanoemulsions with an internal droplet size of 25.7 ± 1.20 nm, a narrow polydispersity index of 0.237 ± 0.129, and 70.6 ± 0.58% transmittance. The in vitro skin permeation study revealed a significantly higher skin penetration and retention of the Tripeptide-3 nanoemulsions compared to the high surfactant microemulsions and coarse emulsions. Skin irritation and oil control efficacy were evaluated in healthy volunteers before and after product application for 28 days. The obtained nanoemulsions not only decreased sebum production but also enhanced skin moisture levels. In conclusion, the meticulously designed nanoemulsions, incorporating suitable excipients, show a promising delivery system for hydrophilic peptides to control sebum overproduction in oily facial skin.

Microwave-assisted hydrogen peroxide digestion followed by ICP-OES for determination of metals in selected fuel oils

This work describes a greener and cost-effective microwave-assisted hydrogen peroxide digestion (MA-HPD) with the addition of 1 mL of HNO3 (70% v/v) to enhance extraction of selected metals (Al, Ba, Cd, Co, Cr, Cu, Mg, Na, Ni, Pb, Sb, Ti and V) in crude-oil, diesel, gasoline and kerosene samples prior to inductively coupled plasma-optical emission spectroscopic (ICP-OES) analysis. The most influential parameters of the MA-HPD method were investigated by using multivariate optimization tools (two-level full factorial and central composite designs) and fuel oil certified reference material (NIST1634c). The optimum conditions were observed to be 245 ℃ microwave temperature, 25 min digestion time, 0.1 g sample mass and 5 M H2O2 were the optimum digestion conditions with accepted accuracy (104.8–117.7%) and precision (≤ 4.1%). In overall, the metals that reported high concentrations in the crude oil, diesel, gasoline, and kerosene samples were Na (51.94–58.86 mg/kg) and Mg (36.08–47.4 mg/kg), while Cu was the lowest (0.55–2.89 mg/kg). When comparing the obtained concentration levels with other literature reports, a conclusion can be drawn that South Africa is importing oils of reasonable quality.

A Cyanoalkyl Silicone GC Stationary-Phase Polymer as an Extractant for Dispersive Liquid–Liquid Microextraction

In this work, three cyanoalkyl silicone GC stationary-phase polymers, namely OV-105, OV-225, and OV-275, were investigated as potential extractants for dispersive liquid–liquid microextraction (DLLME). The OV-225 polymer (cyanopropylmethyl-phenylmethylsilicone) exhibited the cleanest chromatographic background and was extensively studied. The proposed polymer was tested through the DLLME of four non-steroidal anti-inflammatory drugs from aqueous samples, followed by HPLC separation with UV detection at 230 nm. To achieve the maximum enrichment, the experimental conditions that influence the DLLME process were optimized using one-factor-at-a-time and design-of-experiment (DoE) approaches. The extraction variables (polymer mass, dispersive solvent volume, buffer pH, and mixing time) were screened by implementing a two-level full factorial design (FFD). Significant variables were fine-tuned using response surface methodology based on a face-centered central composite design (CCD). The optimum conditions were 10 mg of polymer (extraction medium); 50 µL of tetrahydrofuran (dispersive solvent); 100 µL of phosphate buffer pH 2.75 ([PO43−] = 100 mM); and 3 min of vortex mixing. The addition of salt had a minimal effect on the enrichment factors. In the optimum conditions, enrichment factors up to 46 were achieved using 1.5 mL samples. Calibration curves exhibited correlation coefficients > 0.999 using 4-pentylbenzoic acid as an internal standard. The limits of quantitation were 5 ng/mL for naproxen, 10 ng/mL for diflunisal, 25 ng/mL for indomethacin, and 75 ng/mL for ibuprofen. The analysis of spiked tap water samples showed adequate relative recoveries and precision. In conclusion, the proposed polymer (OV-225) is a potential greener alternative to traditional organic extractants used in DLLME.

A Novel quality-by-design optimized spectrofluorimetric approach for estimation of the oral synthetic adiponectin receptor agonist AdipoRon in different biological matrices: Compliance with greenness metrics

The current study introduces the first analytical approach for the quantitative analysis of adipoRon, a synthetic adiponectin receptor agonist, using a facile, rapid, sensitive, and green spectrofluorimetric method. Nitrogen-doped carbon quantum dots (N-CQDs) were synthesized by adopting a fast microwave-assisted procedure using accessible and natural substrates (orange juice and urea). The suggested synthetic method produced CQDs with narrow particle size distribution (2–10 nm), high fluorescence stability, and good quantum yield (29.3%). The produced fluorescent QDs were used as fluorescent sensors and were quantitatively quenched by increasing adipoRon concentrations. A two-level full factorial design (22 FFD) was used to identify the most critical experimental factors affecting the relative fluorescence intensity of N-CQDs. The fluorescence quenching of N-CQDs by the drug was measured at 417 nm after excitation at 325 nm. Under the optimized conditions, the quenching of N-CQDs' fluorescent intensity displayed acceptable linearity with the adipoRon concentration range of 5.0–20.0 μg/mL with limits of quantitation and detection of 0.843 μg/mL and 0.278 μg/mL, respectively. Owing to the high sensitivity, the suggested method was efficiently applied for adipoRon estimation in different biological matrices, including spiked human plasma, real rat plasma, and liver homogenate samples with high % recoveries (87.41–103.17%) and low %RSD values (<2.87%). The method's greenness was evaluated using two metric tools, the complementary green analytical procedure index (ComplexGAPI) and the Analytical GREENNESS metric approach (AGREE), and the results showed that the method was excellent green. The proposed methodology was validated according to the ICHQ2 (R1) recommendations.

Development, Optimization and Characterization of Glimepiride Nanosuspension with Improved Solubility and Dissolution

Current work describes the development of nanoparticulate suspension (NPs) of glimeperide (GLMP) with enhanced solubility and bioavailability. Using the ultrasonication-assisted precipitation method, GLMP-NP was developed and optimized through the use of a three-factor two-level full factorial design methodology. Drug release, size of a particle, and encapsulation efficiency from nanoparticles were considered as dependent variables while the concentration of Hydroxy propyl cellulose (HPC SSL), Kollicoat IR, and sonication time were considered as independent variables. According to the study, every independent variable significantly affected the dependent variables (p &lt;0.05). The size of the particle GLMP-NP ranged between 159 (F2) to 505 nm (F8) while EE varied from 32 (F8) to 75% (F2). The DR of the GLMP-NP observed at 10 min ranged between 35 (F8) to 100% (F2). A significant enhancement in dissolution rate was observed in GLMP-NPs (F1-F8) in comparison to pure GLMP. It was discovered that pure GLMP dissolved in 27.25 ± 6.8 μg/mL of double-distilled water, while GLMP-NP exhibited 3.50 to 6.58-fold enhancement in saturation solubility. FTIR and DSC analysis revealed excellent compatibility between GLMP and excipients. XRD study confirmed the amorphous nature of the nanoparticles while SEM analysis revealed a smooth surface. In conclusion, this study demonstrates the substantial improvement in dissolution rate and solubility of pure GLMP when formulated as nanoparticles.

Synthesis and design of NaNi1/3Fe1/3Mn1/3O2 cathode materials for long-life sodium-ion batteries

To enable the widespread adoption of residential energy storage, sustainable, low-cost, long-life, and energy-dense battery technologies are required. Sodium-ion offers many of these characteristics, however often the system is tailored for energy rather than cycle life. In this work, the effect of synthesis conditions upon the primary and agglomerated secondary particle size and shape of the sodium-ion cathode material NaNi1/3Fe1/3Mn1/3O2 was investigated for optimization of energy and cycle life. A two-level full factorial experimental design was utilized to examine how the synthesis parameters (pH, molar ratio of ammonia/metal precursor salt, and stirring speed) affect the physical and electrochemical properties. This approach enabled a comprehensive investigation of the main effects and interactions of these parameters. The data from multiple synthesis runs were analyzed using statistical methods and regression analysis. This experimental design provided valuable insights into the relationship between synthesis parameters and material properties. Statistical analysis indicates that both physical and electrochemical properties are mainly controlled through pH and NH4OH, while the effects of stirring speed are less pronounced. The optimal synthetic conditions producing the highest cycling performance were extrapolated from the statistical analysis. A validation experiment showed that particles synthesized with optimum parameters displayed a threefold increase in cycling performance together with uniformly distributed particle size and a high tap density.

Determination of Moisture in Fish Muscles Using a Domestic Microwave Oven

This work highlights using a domestic microwave oven to determine moisture in fish tissues. Also, it compares it with other gravimetric methods established employing a conventional oven (AOAC) and infrared radiation. The optimization of the microwave method was performed utilizing a two-level full factorial design. The AOAC method, which uses a temperature of 105 °C, requires 130 min for the analysis, while the microwave method can be done in 2 min. Intraday and interday tests evaluated the precision of both methods. The determination of the moisture of the fishes Cynoscion acoupa, Argyrosomus regius, Carassius auratus, Sardinella longiceps, Thunnus, Merluccius, Caranx latus, and Brachyplatystoma vaillantii was performed using the microwave and AOAC methods. The analysis of variance and the paired t-test showed no significant differences in the results obtained using these two methods. Also, moisture in other fish tissues was quantified using microwave radiation.

Concentrations of macro and microelement in Brazilian white cheeses: Evaluating sample preparation procedures and estimation of dietary intake

Two sample preparation procedures, microwave-assisted and closed digestion block, were developed to establish the nutritional content of white cheeses. A two-level full factorial design was performed to optimize the decomposition parameters. Under optimum conditions, both procedures led to low dissolved carbon content (< 11% w.w-1) employing 2 mol. L-1 HNO3. Nevertheless, the closed block presented smaller analytical throughput with approximately 11 digested samples h-1 against 20 samples h-1 for MW. Both procedures showed accuracy for Ca, K, P, Na, and Zn and precision with RSD < 10%. The limits of detection ranged from 2.2 (P) to 16 μg g-1 (Ca) (microwave) and 0.8 (K) to 14 μg g-1 (Na) (closed block). The validated procedures were employed to analyze buffalo mozzarella, minas frescal, Ricotta, Coalho, and cottage cheeses. Based on the nutritional analysis, the type of cheese influenced the variation in nutrient content. Furthermore, for all types of cheese, a discrepancy (p < 0.05) was observed between concentrations for at least one analyte, confirming the lack of uniformity in nutritional composition. The recommended daily intake evaluation demonstrated that all samples of buffalo mozzarella and minas frescal cheese analyzed could be considered sources of Ca and P.

Adsorption of methylene blue dye onto modified activated carbon produced from groundnut shells

In this research work, groundnut shells agricultural byproducts were utilized for the production of modified groundnut shell based activated carbon (MGSAC) through the use of phosphoric acid and ethylene-diamine tetraacetic acid disodium salt (Na2EDTA) as an activating agent and a modifier, respectively. A three factor, two-level full factorial design (FFD) was employed for the exploratory design of experiments (DoE). The independent process variables are temperature, activation time, and activating agent concentration for the production of MGSAC in a muffle furnace. The product yield and methylene blue (MB) dye adsorption were considered as the performance indicators for the process. Regression analysis was conducted to examine the influence of process variables on the responses of the process parameters. From the analysis, it was found that the activation temperature has the most significant effects on the MGSAC product yield and the activation time for the adsorption of MB dye. The results obtained showed that the best operating conditions for production of MGSAC were carbonization temperature of 450°C, activation time of 30 min and activating agent concentration of (35 mmol Na2EDTA; 50% H3PO4) which resulted in the product yield of 55.5% MGSAC, and 99.6% MB dye adsorption. It was also observed that experimental values obtained were in good agreement with the values predicted by the model. Hence, the two-level FFD DoE technique demonstrated worthwhile features in disclosing the dominant factors that affect the production of modified groundnut shell based activated carbon. The products appear to be promising adsorbents for the adsorption of cationic MB dye from wastewaters.

Optimization of wind off-grid system for remote area: Egyptian application

Due unexpected nature of renewable energy systems, the (Wind/Diesel/Battery) (W/D/B) off-grid system has initially been investigated at a South Sinai location in Egypt for home-scale consumption. Eight different systems, each of which consists of a small wind turbine, storage batteries, and diesel generator, are investigated in accordance with the varying needs of the power loads and seasonal weather data. The major goal is to investigate how adding wind power as an energy source will affect the price of electricity generated while taking into account the cost of reducing CO2 emissions as an external benefit of the wind turbine, which emits no pollutants during operation. In order to compare a Taguchi OA design to a two-level full factorial design to evaluate the systems at two separate sites (South Sinai and the Western Desert in Egypt), a design evaluation tool in DOE++ will be used. To pinpoint the crucial variables and analyze the impact of six different factors on eight different sets, Taguchi OA is used. The proportion of power shortfall is a production indicator, while the net present cost (NPC) and cost of energy (COE) are used as economic indicators. The simulation results demonstrate that W/D/B systems are economically viable for the hypothetical community site when using HOMER software, with electricity generated at a cost of about 0.285$/kWh without accounting for external benefits and 0.221$/kWh if CO2 emissions are competitive with diesel-only systems, where COE is 0.432$/kWh. As a new evaluation approach, the Box-Cox transformation calculated the best λ is about −2 at the two locations, indicating similar technique behaviors, and the fitted probability shows, meaning that the significant impact of system components are wind turbines. Regression model of CO2 emission is demonstrated to be successful for estimates at the Western Desert location than the South Sinai region

Comparison of Tool Wear, Surface Roughness, Cutting Forces, Tool Tip Temperature, and Chip Shape during Sustainable Turning of Bearing Steel.

In this study, a comparison of measured cutting parameters is discussed while machining AISI 52100 low-alloy hardened steel under two different sustainable cutting environments, those in which a dry and minimum quantity lubrication (MQL) medium are used. A two-level full factorial design method has been utilized to specify the effect of different experimental inputs on the turning trials. Experiments were carried out to investigate the effects of three basic defining parameters of turning operation which are namely cutting speed, cutting depth, feed rate effects and also the effects of the cutting environment. The trials were repeated for the combination of different cutting input parameters. The scanning electron microscopy imaging method was used to characterize the tool wear phenomenon. The macro-morphology of chips was analyzed to define the influence of cutting conditions. The optimum cutting condition for high-strength AISI 52100 bearing steel was obtained using the MQL medium. The results were evaluated with graphical representations and they indicated the superiority of the pulverized oil particles on tribological performance of the cutting process with application of the MQL system.

Quality-by-design driven analytical method (AQbD) development and validation of HPLC–UV technique to quantify rivastigmine hydrogen tartrate in lipidic nanocarriers: Forced degradation, and assessment of drug content and in vitro release studies

The main purpose of current investigation was to design and further validate a technique for the quantitative determination of rivastigmine hydrogen tartrate (RHT), a cholinesterase inhibitor in the nano formulations. With the employment of a reverse phase C18 column and a very simple mobile phase, an isocratic HPLC–UV analysis technique was developed, optimized, and validated following ICH Q2 (R1) requirements along with the inculcation ofAnalytical Quality-by-Design (AQbD) methodology. A two-level full factorial screening design was applied to filter out the variables influencing responses, followed by the application of central composite design (CCD) to further optimize the method using Design-Expert® software. Analyses were performed at room temperature with 0.9 mL. min−1 flow rate and detection wavelength of 215 nm. The optimized HPLC technique exhibited superior linearity, selectivity, and precision. The inherent stability of RHT was evaluated using the optimized method byconductingforced degradation studies. The RHT peak was clear and unaffected by matrix interference in the specimens from the forced degradation studies, drug content analysis, and in vitro release study. The assay had a limit of detection (LOD) of 14.32 ng. mL−1 and a limit of quantitation (LOQ) of 43.40 ng. mL−1. With acceptable intra- and interday precision, the methodologywas confirmedto berobust. The devised stability-indicating HPLC technique for analyzing RHT content, its stability in the nano formulations, and drug release in vitro proved to be selective, accurate, sensitive, and consistent.

Different Aspects of Machinability in Turning of AISI 304 Stainless Steel: A Sustainable Approach with MQL Technology

Machining of AISI 304 austenitic stainless steel is considered to be difficult due to its structural aspects and low thermal conductivity, which leads to increased temperatures during machining. To overcome the challenges of machining AISI 304 stainless steel, several cooling and lubricating techniques have been developed. The main objective of this experimental study is to evaluate the different turning conditions of AISI304 stainless steel under dry and minimum quantity lubrication (MQL) environment conditions. The machining experiments were conducted using a two-level full factorial design method and utilized a TiC-coated cutting tool. The tool-tip temperature, cutting force and surface roughness were analyzed regarding three cutting parameters namely, cutting speed, feed rate and cutting depth. Also, chip macro-morphology was investigated to define the interaction at the tool-chip-workpiece region. The cutting medium affects the surface roughness significantly (more than 100%) for all cutting parameter values. In some environmental cutting conditions, high cutting speed provides 10% lesser surface roughness than low cutting speed parameters. Also, the cutting force decreases by 20% in low feed rate machining conditions. However, the effect of this parameter disappeared for cutting forces in high feed rates and low cutting depth conditions in both MQL and dry environments. Cutting speed was observed as the most influential factor on surface roughness, followed by feed rate. The depth of cut was the main parameter that caused the temperature to increase in the dry machining environment.

Two-Level Full Factorial Design Approach for the Analysis of Multi-Lane Highway Section under Saturated and Unsaturated Traffic Flow Conditions

Oversaturation of highways occurs due to their inadequate assessment and design. In this paper, we propose both a mathematical queuing model and a Discrete-Event Simulation (DES) framework based on Newell’s triangular flow-density relationship for the performance analysis of a multi-lane highway section. The proposed framework is a finite capacity queuing system, which captures an increase in the flow with the vehicle density up to the capacity of the section in an unsaturated condition and a decrease in the flow in the case of a saturated condition, depicting the actual traffic conditions on the highway section. First, the Birth–Death Process is used to build the mathematical queuing model (BDP), and the average number of vehicles (average queue length) and blocking probability on the highway section are estimated. Then, the accuracy of the mathematical queuing model is verified by the proposed DES framework. The “significance and effects” of different design factors are evaluated using the two-level full factorial design technique. The analysis of the experimental results reveals that the length of the highway section and the number of lanes are the most significant factors affecting the average queue length and blocking probability, while the jam density only has a significant effect on the average queue length and does not affect the blocking probability. In case of a two-way interaction, the combined effect of the “length-lanes” significantly affects the average queue length. In the end, a multiple-factor linear regression model is also developed for the prediction of the average number of vehicles on the highway section based on the design factors.

Conductive Filament Composites from Waste Battery Rod-Derived Exfoliated Graphite for Fused Deposition Modeling 3D Printing: A Two-Level Factorial Design Optimization Study

This study used carbon rods from spent zinc-carbon batteries as a source of exfoliated graphite (EG) to produce conductive filament composites for fused deposition modeling 3D printing. The EG filler was prepared through microwave irradiation, while the resulting 3D printable electroconductive EG composites were prepared using polylactic acid (PLA) and polyethylene glycol (PEG) as the polymer matrix and compatibilizer, respectively, via a sonication-assisted solution blending and melt extrusion process. A two-level full factorial design was employed to fully investigate the influence of filament production parameters such as EG loading, PEG:PLA ratio, and sonication time on the resistivity (i.e., conductivity-1) of the prepared composites. Analysis of variance showed that both EG loading and sonication time had significant effects on the resistivity of the composites. The optimum electrical resistivity of the new EG filament composites was found to be 916.418 Ω-cm (maximum conductivity = 1.091 x10-3 S/cm) at EG loading = 45 % w/w, PEG:PLA ratio = 1:10, and sonication time = 2 hours. The conductivity of the 3D printed composites was also correlated with EG amount by the power law model of percolation theory, resulting in an electrical percolation threshold at around 35 % w/w of EG. Our filament composites enable the fabrication of high-value conductive materials from waste resources for sustainable additive manufacturing in the electronics industry.

Application of quality-by-design for adopting an environmentally green fluorogenic determination of benoxinate hydrochloride in eye drops and artificial aqueous humour

Herein, a sensitive and selective spectrofluorimetric method has been developed for the determination of the ocular local anesthetic benoxinate hydrochloride (BEN-HCl) in eye drops and artificial aqueous humour. The proposed method is based on the interaction of fluorescamine with the primary amino group of BEN-HCl at room temperature. Following the excitation of the reaction product at 393 nm, the emitted relative fluorescence intensity (RFI) was measured at 483 nm. The key experimental parameters were carefully examined and optimized by adopting an analytical quality-by-design approach. The method used a two-level full factorial design (24 FFD) to obtain the optimum RFI of the reaction product. The calibration curve was linear at the range of 0.10–1.0 μg/mL of BEN-HCl with sensitivity down to 0.015 μg/mL. The method was applied for analyzing the BEN-HCl eye drops and could also assess its spiked levels in artificial aqueous humour with high % recoveries (98.74–101.37%) and low SD values (≤ 1.11). To investigate the green profile of the proposed method, a greenness assessment was performed with the aid of the Analytical Eco-Scale Assessment (ESA) and GAPI. The developed method obtained a very high ESA rating score in addition to being sensitive, affordable, and environmentally sustainable. The proposed method was validated according to ICH guidelines.

Synthesis and Application of a New Polymer with Imprinted Ions for the Preconcentration of Uranium in Natural Water Samples and Determination by Digital Imaging.

This work proposes the synthesis of a new polymer with imprinted ions (IIP) for the pre-concentration of uranium in natural waters using digital imaging as a detection technique. The polymer was synthesized using 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (Br-PADAP) for complex formation, ethylene glycol dimethacrylate (EGDMA) as a crosslinking reagent, methacrylic acid (AMA) as functional monomer, and 2,2'-azobisisobutyronitrile as a radical initiator. The IIP was characterized by Fourier transform infrared spectroscopy and scanning electron microscopy (FTIR). Uranium determination was performed using digital imaging (ID), and some experimental conditions (sample pH, eluent concentration, and sampling flow rate) were optimized using a two-level full factorial design and Doelhert response surface methodology. Thus, using the optimized conditions, the system allowed the determination of uranium with detection and quantification limits of 2.55 and 8.51 µg L-1, respectively, and a pre-concentration factor of 8.2. All parameters were determined using a 25 mL sample volume. The precision expressed as relative deviation (RSD%) was 3.5% for a solution with a concentration of 50 µg L-1. Given this, the proposed method was used for the determination of uranium in four samples of natural waters collected in the city of Caetité, Bahia, Brazil. The concentrations obtained ranged from 35 to 75.4 μg L-1. The accuracy was evaluated by the addition/recovery test, and the values found ranged between 91 and 109%.

Analytical quality-by-design approach for development and validation of HPLC method for the simultaneous estimation of omarigliptin, metformin, and ezetimibe: application to human plasma and dosage forms

A simple, selective, and sensitive RP-HPLC method was proposed for the simultaneous determination of two co-administered antidiabetic drugs (omarigliptin and metformin) with an anti-hyperlipidemic drug (ezetimibe) in a medicinally-recommended ratio of 2.5:50:1, respectively. The proposed procedure was optimized by adopting a quality-by-design approach. The influence of different factors on chromatographic responses was optimized by applying the two-level full factorial design (25). The optimum chromatographic separation was achieved using Hypersil BDS C18 column at 45 °C, and the mobile phase pumped isocratically composed of methanol: potassium dihydrogen phosphate buffer (6.6 mM; pH 7, 67:33% v/v) at a flow rate of 0.814 mL/min using 235 nm as a detection wavelength. The developed method was capable of separating this novel mixture in less than 8 min. The calibration plots of omarigliptin, metformin, and ezetimibe showed acceptable linearity over the ranges of 0.2-2.0, 0.5–25.0, and 0.1-2.0 µg/mL with quantitation limits of 0.06, 0.50, and 0.06 µg/mL, respectively. The proposed method was successfully applied to determine the studied drugs in their commercial tablets with high % recoveries (96.8-102.92%) and low % RSD values (less than 2%). The applicability of the method was extended to the in-vitro assay of the drugs in spiked human plasma samples with high % recoveries (94.3-105.7%). The suggested method was validated in accordance with ICH guidelines.