Maximizing the Use of Ivermectin Transethosomal Cream in the Treatment of Scabies.

In an effort to tackle the skin reactions frequently observed with topical application of ivermectin (IVM), a study was conducted to develop and optimize transethosomes (TESMs) loaded with IVM for scabies treatment. A three-factor, two-level (23) full factorial design was employed. Soyabean phosphatidylcholine concentration (A), ethanol concentration (B) and Span 60 amount (C) were studied as independent factors, while entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and drug release after 6 h (Q6h) were characterized. The skin sensitivity of the optimized formulation was evaluated by skin irritation test and histopathological examination. The EE% ranged from 88.55 ± 0.576% to 94.13 ± 0.305%, PS was from 318.033 ± 45.61 nm to 561.400 ± 45.17 nm, PDI was from 0.328 ± 0.139 to 0.671 ± 0.103, ZP was from -54.13 ± 1.09 mV to -60.50 ± 2.34 mV and Q6h was from 66.20 ± 0.30% to 93.46 ± 0.86%. The IVM-loaded transethosomal cream showed lower skin irritation and a more intact epidermal layer with intact keratinocyte, compared to the marketed cream which showed severe destruction of the keratin layer. Therefore, patient compliance can be improved by encapsulating IVM within TESMs to minimize its skin reactions.

Green analytical quality by design RP-HPLC technique with fluorimetric detection for simultaneous assay of cinnarizine and dompridone.

A green and sensitive factorial design-assisted reversed-phase high-performance liquid chromatography (RP-HPLC) approach with fluorimetric detection has been developed for simultaneous determination of cinnarizine and domperidone in pure materials, commercial single and combined tablets. Both drugs are co-formulated in one dosage form and are commonly used for the effective treatment of motion sickness in the ratio of 4 : 3 for cinnarizine and domperidone, respectively. To achieve the developed method's best performance and reliability, a 23 full factorial design was applied during the optimization of chromatographic conditions. Subsequently, isocratic elution on a C18 column with a mobile phase mixture of methanol and 0.02 M potassium dihydrogen phosphate buffer (85 : 15 v/v, pH 3.0) was performed to achieve the best separation. Moreover, the flow rate of 0.8 ml min-1 was applied during the analysis with fluorescence detection at λex 283 nm/λem 324 nm. The elution process was time effective; it consumed less than 6 min for a complete run as retention time for cinnarizine and domperidone, was 4.5 and 3.5, respectively. Good linearity of the proposed method was achieved within the concentration ranges of 0.2-4.5 and 0.4-5.0 µg ml-1 for domperidone and cinnarizine, respectively. The suggested approach was carefully validated according to the International Council for Harmonization (ICH) guidelines. Moreover, green analytical procedure index (GAPI), national environmental methods index (NEMI), analytical greenness (AGREE) and analytical eco-scale methods were applied to assess and confirm method greenness.

Optimization and quality evaluation of functional pasta made from germinated finger millet, buckwheat, and black gram.

The investigation was conducted to optimize process variables to manufacture functional pasta from composite flour. The selected grains were steeped, germinated, dried, and milled to produce flour. The flours were mixed at optimized proportions (57.31% buckwheat flour, 12.68% finger millet flour, and 30% paheli dal flour) to produce composite flour. The full factorial experimental design opted for optimization of process variables namely, moisture content (mc) (28, 30, 32, and 34%) and mixing speed (60, 80, 100, and 120 rpm). The optimized multi-grain pasta showed shorter processing time, in-range cooking loss, and higher cooking weight and water absorption capacity (WAC). The highest overall acceptability was recorded for multi-grain pasta processed at 60 rpm with an initial mc of 32%. Proximate analysis of optimized multi-grain pasta showed that pasta contained protein (13.95%), crude fiber (5.05%), ash (2.05%), a lower amount of fat (0.74%), and carbohydrates (71.71%).

Quality-by-Design-Driven Nanostructured Lipid Scaffold of Apixaban: Optimization, Characterization, and Pharmacokinetic Evaluation.

Apixaban, an anticoagulant, is limited in its efficacy due to poor solubility, low bioavailability, and extensive metabolism. This study investigates the application of nanostructured lipid carriers (NLCs) to enhance the bioavailability of Apixaban. NLCs were prepared using the high-pressure homogenization method. The influence of independent variables, viz., the amount of Tween 80, HPH pressure, and the number of HPH cycles, were studied using a 23 factorial design. The average particle size, PDI, zeta potential, and entrapment efficiency of the optimized NLCs were found to be 232 ± 23 nm, with 0.514 ± 0.13 PDI and zeta potential of about -21.9 ± 2.1 mV, respectively. Additionally, concerning the thermal and crystallographic properties of the drug, the NLCs showed drug entrapment without altering its potency. The in-vitro drug release studies revealed an immediate release pattern, followed by sustained release for up to 48 h. In-vivo pharmacokinetic experiments demonstrated that Apixaban-loaded NLCs exhibited higher values of t1/2 (27.76 ± 1.18 h), AUC0-∞ (19,568.7 ± 1067.6 ng·h/mL), and Cmax (585.3 ± 87.6 ng/mL) compared to free drugs, indicating improved bioavailability. Moreover, a decrease in the elimination rate constant (Kel) reflected the sustained effect of Apixaban with NLCs. NLCs offer improved oral absorption rates and enhanced therapeutic impact compared to free drugs, potentially reducing dose frequency and improving patient outcomes.

Microfluidic preparation and optimization of (Kollicoat ® IR-b-PCL) polymersome for co-delivery of Nisin-Curcumin in breast cancer application.

This work aimed to develop amphiphilic nanocarriers such as polymersome based diblock copolymer of Kollicoat ® IR -block-poly(ε-caprolactone) (Kollicoat ® IR-b-PCL) for potential co-delivery of Nisin (Ni) and Curcumin (CUR) for treatment of breast cancer. To generate multi-layered nanocarriers of uniform size and morphology, microfluidics was used as a new technology. In order to characterise and optimize polymersome, design of experiments (Design-Expert) software with three levels full factorial design (3-FFD) method was used. Finally, the optimized polymersome was produced with a spherical morphology, small particle size (dH < 200 nm), uniform size distribution (PDI < 0.2), and high drug loading efficiency (Ni 78 % and CUR 93 %). Furthermore, the maximum release of Ni and CUR was found to be roughly 60 % and 80 % in PBS, respectively. Cytotoxicity assays showed a slight cytotoxicity of Ni and CUR -loaded polymersome (N- Ni /CUR) towards normal cells while demonstrating inhibitory activity against cancer cells compared to the free drugs. Also, the apoptosis assays and cellular uptake confirmed the obtained results from cytotoxic analysis. In general, this study demonstrated a microfluidic approach for preparation and optimization of polymersome for co-delivery of two drugs into cancer cells.

Application of 32 factorial design for loratadine-loaded nanosponge in topical gel formulation: comprehensive in-vitro and ex vivo evaluations.

Loratadine (LoR) is a highly lipophilic and practically insoluble in water, hence having a low oral bioavailability. As it is formulated as topical gel, it competitively binds with the receptors, thus reducing the side-effects. The objective of this study was to prepare LoR loaded nanosponge (LoR-NS) in gel for topical delivery. Nine different formulations of emulsion were prepared by solvent evaporation method with polyvinyl alcohol (PVA), ethyl cellulose (EC), and dichloromethane (DCM). Based on 32 Full Factorial Design (FFD), optimization was carried out by varying the concentration of LOR:EC ratio and stirring rate. The preparations were subjected for the evaluation of particle size (PS), in vitro release, zeta potential (ZP) and entrapment efficiency (EE). The results revealed that the NS dispersion was nanosized with sustained release profiles and significant PS. The optimised formulation was formulated and incorporated into carbopol 934P hydrogel. The formulation was then examined to surface morphological characterizations using scanning electron microscopy (SEM) which depicted spherical NS. Stability studies, undertaken for 2 months at 40 ± 2 °C/75 ± 5% RH, concluded to the stability of the formulation. The formulation did not cause skin irritation. Therefore, the prepared NS hydrogel proved to be a promising applicant for LoR as a novel drug delivery system (NDDS) for safe, sustained and controlled topical application.

Thermo-Mechanical Characterization of Metal-Polymer Friction Stir Composite Joints-A Full Factorial Design of Experiments.

With the increasing demand for lighter, more environmentally friendly, and affordable solutions in the mobility sector, designers and engineers are actively promoting the use of innovative integral dissimilar structures. In this field, friction stir-based technologies offer unique advantages compared with conventional joining technologies, such as mechanical fastening and adhesive bonding, which recently demonstrated promising results. In this study, an aluminum alloy and a glass fiber-reinforced polymer were friction stir joined in an overlap configuration. To assess the main effects, interactions, and influence of processing parameters on the mechanical strength and processing temperature of the fabricated joints, a full factorial design study with three factors and two levels was carried out. The design of experiments resulted in statistical models with excellent fit to the experimental data, enabling a thorough understanding of the influence of rotational speed, travel speed, and tool tilt angle on dissimilar metal-to-polymer friction stir composite joints. The mechanical strength of the composite joints ranged from 1708.1 ± 45.5 N to 3414.2 ± 317.1, while the processing temperature was between 203.6 ± 10.7 °C and 251.5 ± 9.7.

Red Dragon Fruit Peels: Effect of Two Species Ratio and Particle Size on Fibre Quality and Its Application in Reduced-Fat Alpaca-Based Sausages.

This research aimed to assess the influence of red dragon fruit peels ratio (RDF-PR) from two species, Hylocereus hybridum (HH) and Hylocereus undatus (HU), and particle size (PS) on quality parameters of red dragon fruit peel powder (RDF-PP) and its further application in emulsified alpaca-based sausages as partial substitutes of pork-back fat. A three-level full factorial design (nine treatments) was employed to evaluate the effect of RDF-PR (HH(0%):HU(100%), HH(50%):HU(50%), and HH(100%):HU(0%)) and PS (499-297, 296-177, and <177 µm) on the dependent variables: L*, a*, b*, C, h°, water-holding capacity, oil-holding capacity, swelling capacity, pectin yield, degree of esterification (analysed through FT-IR), and crude fibre content. The data analysed through a response surface methodology showed that treatment one (T1) is the best with the optimised conditions at 100% HU RDF-PR and PS of <177 µm. The statistical validation of T1 exhibited the highest water-holding capacity (32.1 g/g peel), oil-holding capacity (2.20 g oil/g peel), and pectin yield (27.1%). A completely randomised design (four formulations) was then used to assess the effect of partial replacement of pork-back fat by T1 in emulsified alpaca-based sausages on the colourimetric, physicochemical, and texture properties (hardness, chewiness, cohesiveness, springiness, adhesiveness, and adhesive force). Likewise, a sensory hedonic scale was employed to evaluate the appearance, colour, odour, flavour, texture, and overall acceptability of sausages. The results revealed that 65.7% of pork-back fat content was successfully replaced compared with a control formulation. Additionally, F3 showed significantly (p < 0.05) better colourimetric, physicochemical, and textural characteristics, such as lower hardness (34.8 N) and chewiness (21.7 N) and higher redness (a* = 19.3) and C (22.9), compared to a control formulation. This research presents RDF-PP as a promising fat substitute for developing healthier, reduced-fat meat products using fibre-rich agroindustry by-products.

Analysis of Compressive Strength of Anhydrite Binder Using Full Factorial Design.

Flue gas desulfurization gypsum (FGD gypsum) is obtained from the desulphurization of combustion gases in fossil fuel power plants. FGD gypsum can be used to produce anhydrite binder. This research is devoted to the investigation of the influence of the calcination temperature of FGD gypsum, the activators K2SO4 and Na2SO4, and their amount on the compressive strength of anhydrite binder during hydration. The obtained results showed that as the calcination temperature increased, the compressive strength of anhydrite binder decreased at its early age (up to 3 days) and increased after 28 days. The compressive strength of the anhydrite binder produced at 800 °C and 500 °C differed more than five times after 28 days. The activators K2SO4 and Na2SO4 had a large effect on the hydration of anhydrite binder at its early age (up to 3 days) in comparison with the anhydrite binder without activators. The presence of the activators of either K2SO4 or K2SO4 almost had no influence on the compressive strength after 28 days. To determine which factor, the calcination temperature of FGD gypsum (500-800 °C), the hydration time (3-28 days) or the amount (0-2%) of the activators K2SO4 and Na2SO4, has the greatest influence on the compressive strength, a 23 full factorial design was applied. Multiple linear regression was used to develop a mathematical model and predict the compressive strength of the anhydrite binder. The statistical analysis showed that the hydration time had the strongest impact on the compressive strength of the anhydrite binder using activators K2SO4 and Na2SO4. The activator K2SO4 had a greater influence on the compressive strength than the activator Na2SO4. The obtained mathematical model can be used to forecast the compressive strength of the anhydrite binder produced from FGD gypsum if the considered factors are within the same limiting values as in the suggested model since the coefficient of determination (R2) was close to 1, and the mean absolute percentage error (MAPE) was less than 10%.

Dataset of manual metal arc welded heterogeneous thin steel plates AISI1018 AND AISI4340.

Advancement in technology demands the joining of heterogeneous metals of low and high-carbon steel grades. In this investigation, AISI1018 low and AIS4340 medium carbon steels were welded to form a heterogeneous thin metal joint using the Manual Metal Arc Welding (MMAW) method. Experimental variations of welding current, electrode position, and weld orientation are selected as the MMAW parameters. The trials are planned using the Full Factorial Design (FFD) and the trial results are analysed using Analysis of Variance (ANOVA) and regression methods. A computerized tensile testing machine (TM2101N) was used to test the tensile strength of the welded specimens that were prepared in accordance with the ASTM E646 - 98 standards. The prediction model for tensile strength was generated based on regression analysis. The ANOVA and prediction model helped in studying the effect of the MMAW parameters.

Phyto-assisted synthesis of CuO/industrial waste derived biochar composite for adsorptive removal of doxycycline hydrochloride and recycling of spent biochar as green energy storage device.

The highest exposure of Endocrine disrupting compounds (EDC) into the water bodies as a result of extensive production and application of Covid-19 related drugs is a growing concern now a days. Herein, a novel nanocomposite material was developed by impregnating green synthesized copper oxide nanoparticles on the porous surface of fabric waste derived biochar to eliminate the concerned EDCs along with a sustainable disposal strategy for the spent adsorbent. Morphological characterizations by Field emission scanning electron microscopy confirmed the formation of hierarchical porous structured material. X-ray analysis revealed presence of both amorphous nature of biochar matrix as well as the crystalline nature attributed from monodispersion of copper oxide nanoparticles onto biochar surface. Batch sorption study showed removal of doxycycline hydrochloride (DOX) of >97% after 2 h at pH 7, 30 mg L-1 initial concentration of DOX and 2 g L-1 of adsorbent dose at room temperature after a two-step optimization process. Spectroscopic study and Raman shift suggested that pore filling, strong complexation and electrostatic interactions maximise the adsorption of DOX in the CuO/biochar composite as compared to the pristine biochar. However disposal of spent adsorbent is a crucial aspect for the environment and therefore, a sustainable recycling strategy for DOX loaded adsorbent as electrode material has been proposed for the first time in this study. Maximum specific capacitance value was observed in the range of 221.9-297.3 F g-1 for the DOX loaded nanocomposite at 1 mV s-1 comparable with other reported heteroatom-doped carbonaceous material as electrode. Therefore the excellent adsorption capacity of green synthesized CuO/biochar composite and its recycling after DOX adsorption can be recommended as a sustainable solution for mitigation of pharmaceuticals from wastewater. A detail study on degradation of DOX into eco-friendly products and its cost-effectiveness would be beneficial to suggest appropriate mitigation strategy for such compounds.

Extracellular lipase production by Yarrowia lipolytica under magnetic fields.

This study aimed at estimating cultivation conditions to enable Yarrowia lipolytica NNRL Y-1095 to produce extracellular lipase and at evaluating the influence of magnetic fields (MF) on the lipase production and on its catalytic conditions. Culture conditions of carbon sources and surfactant defined to produce extracellular lipase were 10 g L-1 glucose, 15 g L-1 olive oil and 2 g L-1 Triton X-100. The highest lipase activity (34.8 U mL-1) was reached after 144 h when MFs were applied from 72 to 144 h of culture. It corresponds to an increase of 287.5% by comparison with the highest lipase activity in the control culture. MF application from 72 to 144 h did not change the optimal temperature of lipase, which was 37 °C, by comparison with the control. However, the optimal pH of the control was 7.0 while the one of lipase produced with MF was 8.0. Findings highlighted that the presence of MFs led to increase in synthesis of lipase by Y. lipolytica, with changes in the catalytic profile. This is one of the first studies of MF application to Y. lipolytica NRRL Y-1095 cultures to produce lipase.

Potential of Antarctic lipase from Acinetobacter johnsonii Ant12 for treatment of lipid-rich wastewater: screening, production, properties and applications.

The present study aimed to screen and optimize lipase production by the Antarctic strain Acinetobacter johnsonii Ant12 for lipid-rich wastewater treatment. Lipase production was successfully enhanced threefold through optimization of culture conditions. The optimum crude lipase activity was observed at 50 °C with high stability in a wide temperature range. The lipase also exhibited high activity and stability in the presence of solvents, metal ions, and surfactants. The crude lipase was used for the treatment of lipid-rich wastewater, which poses a significant challenge, as traditional removal methods are often inefficient or non-eco-friendly. In this study, bioaugmentation with Ant12 resulted in substantial lipid reduction in synthetic as well as real-world wastewater. Multiple linear regression analysis showed that lipid concentration and time were the most significant factors influencing lipid degradation. Bioaugmentation of real-world wastewater with Ant12 cells resulted in 84% removal of lipids in 72 h, while its crude lipase degraded 73.7% of lipids after 24 h. Thus, the specific rate of lipid degradation was higher for crude lipase (0.095/h) than the whole cell treatment (0.031/h). Economic analysis revealed that crude lipase production was much cheaper, faster and more eco-friendly than purified or partially purified lipase production, which justifies its use in wastewater treatment. The high activity of enzyme also implicates its application as a detergent additive. In our knowledge, it is the first study to establish A. johnsonii isolate from Antarctica for lipid-rich wastewater treatment.

Fabrication and Synthesis of Thiococlchicoside loaded Matrix type Transdermal Patch.

BACKGROUND: The goal of this work was to synthesize and fabricate matrix type transdermal patches based on a combination of polymers (Eudragit L100, HPMC and PVP K30), plasticizer and crosslinking agents (propylene glycol and triethyl citrate) and adhesives (Dura Tak 87-6908) to increase Thiocolchicoside (THC) absorption via topical route. This method allows avoidance of first-pass metabolism along with a consistent and extended duration of therapeutic activity. METHODS: Fabrication and casting of polymeric solutions containing THC was done either in petri plates or through lab coater to get transdermal patches. Finally, the formulated patches were studied for their physicochemical and biological evaluation using scanning electron microscopy, FTIR, DSC, XRD and ex-vivo permeation studies using pig ear skin. RESULTS: FTIR studies confirm that the THC characteristics peaks (carbonyl (Amide I) at 1525.5 cm-1, C=O stretching (tropane ring) at 1664.4 cm-1, Amide II band (N-H stretching) at 3325.9cm-1, thioether band at 2360.7cm-1, and OH group stretching band at 3400.2 cm-1) are still present in the polymer mixture even after formulation as a transdermal patch, indicating compatibility among all excipients. While on the other hand, DSC studies confirm endothermic peaks for all the polymers along with THC with the highest enthalpy of 65.979 J/g, which is an indicator of sharp endothermic peak at 198℃, leading to the melting of THC. The percentage drug content and percentage moisture uptake of all the formulation was found in the range of 96±2.04 to 98.56±1.34% and 4.13±1.16 to 8.23±0.90%, respectively. Drug release and release kinetics studies confirm that it is dependent on the composition of individual formulation. CONCLUSION: All these findings support the possibility of using suitable polymeric composition, as well as proper formulation and manufacturing circumstances, to create a one-of-a-kind technology platform for transdermal drug administration.

Step-by-step full factorial design to optimize a quantitative sandwich ELISA.

In this work, a quantitative sandwich ELISA was optimized, through a full factorial design of experiments (DOE) in successive steps of a preliminary protocol obtained by the method of one factor at a time (OFAT). The specificity of the optimized ELISA, the lower limit of quantification, the quantification range and the analytical sensitivity of the antigen quantification curve were evaluated, in comparison with the curve obtained from the preliminary protocol. The full factorial DOE was linked to a simple statistical processing, which facilitates the interpretation of the results in those laboratories where there is no trained statistician. The step-by-step optimization of the ELISA and the successive incorporation into the protocol of the best combination of factors and levels, allowed obtaining a specific immunoassay, with an analytical sensitivity 20 times greater and with a lower limit of antigen quantification that decreased from 156.25 at 9.766 ng/mL. As far as we know, there are no reports of optimization of an ELISA following the step-by-step scheme used in this work. The optimized ELISA will be used for the quantification of the TT-P0 protein, the active principle of a vaccine candidate against sea lice.

Enhancing the dissolution rate of poorly soluble drug Febuxostat using spray dried amorphous solid dispersion technique / Mejora de la tasa de disolución del fármaco poco soluble Febuxostat utilizando la técnica de dispersión de sólido amorfo secado por aspersión

Introducción: El febuxostat pertenece a los fármacos clase II del Sistema de Clasificación Biofarmacéutica, los cuales presentan baja solubilidad y alta permeabilidad. La dispersión sólida amorfa es una de las técnicas que pueden ser útiles para mejorar la solubilidad y las características del polvo. Objetivo: optimizar la concentración de polímeros hidrofílicos e hidrofóbicos para mejorar la velocidad de disolución y la solubilidad de las tabletas de febuxostat. Métodos: La dispersión sólida amorfa de febuxostat se preparó mediante el método de secado por aspersión utilizando Kolliphor P237 (1:2). Esta dispersión sólida amorfa se utilizó además para comprimir el comprimido. Para mejorar la solubilidad y la tasa de disolución, se aplicó un diseño factorial completo para optimizar la concentración crítica de KollidonSR e hidroxi propil metil celulosa (HPMC K4M). Los comprimidos preparados se caracterizaron por parámetros de precompresión y poscompresión. Resultados: La velocidad de liberación del fármaco se mantuvo mediante la formulación de una técnica de dispersión sólida amorfa. Se encontró que el lote optimizado (FSRT-OB) era apto para la liberación promedio del 93,30 % del fármaco en forma de liberación sostenida hasta 12 horas. Los datos de la cinética de liberación sugieren que la liberación del fármaco estuvo controlada por una combinación de mecanismo de relajación de cadena y difusión. Se encontró que la concentración optimizada para Kollidon SR y HPMC K4M era 38,50 % y 7,72 % respectivamente. Conclusión: La técnica de dispersión sólida amorfa es útil para mejorar la solubilidad, la velocidad de disolución y la biodisponibilidad de la tableta de Febuxostat. (AU)

Introduction: Febuxostat belongs to Biopharmaceutical classification system (BCS) class II drugs, which have low solubility and high permeability. Amorphous solid dispersion is one of the techniques which can be useful to improve solubility and powder characteristics. Objective: To optimize the concentration of hydrophilic and hydrophobic polymers to improve the dissolution rate and solubility of febuxostat tablets. Methods: The amorphous solid dispersion of febuxostat was prepared by spray drying method using Kolliphor P237 (1:2). This amorphous solid dispersion was further used to compress the tablet. To improve solubility and dissolu-tion rate, a full factorial design was applied to optimize the critical concentration of Kollidon SR and hydroxypropyl methyl cellulose (HPMC K4M). The prepared tablets were characterized by pre-compression and post-compression parameters. Result: The rate of drug release was sustained by formulating an amorphous solid dispersion technique. The optimized batch (FSRT-OB) was found to be fit for release average 93.30 % of the drug in sustain release manner up to 12hrs. The release kinetic data suggests that the drug release was controlled by combination of diffusion and chain relaxation mechanism. The optimized concentration for Kollidon SR and HPMC K4Mwas found to be 38.50 % and 7.72 % respectively. Conclusion: Amorphous solid dispersion technique is useful to enhance solubility, dissolution rate, and bioavail-ability of the Febuxostat tablet. (AU)

Mechanical strength predictability of full factorial, Taguchi, and Box Behnken designs: Optimization of thermal settings and Cellulose Nanofibers content in PA12 for MEX AM.

Optimization of reinforced nanocomposites for MEX 3D-printing remain strong industrial claims. Herein, the efficacy of three modeling methods, i.e., full factorial (FFD), Taguchi (TD), and Box-Behnken (BBD), on the performance of MEX 3D printed nanocomposites was investigated, aiming to reduce the experimental effort. Filaments of medical-grade Polyamide 12 (PA12) reinforced with Cellulose NanoFibers (CNF) were evolved. Besides the CNF loading, 3D printing settings such as Nozzle (NT) and Bed (BΤ) Temperatures were optimization goals aiming to maximize the mechanical response. Three parameters and three levels of FFD were compliant with the ASTM-D638 standard (27 runs, five repetitions). An L9 orthogonal TD and a 15 runs BBD were compiled. In FFD, wt.3%CNF, 270 °C NT, and 80 °C BΤ led to 24% higher tensile strength compared to pure PA12. TGA, RAMAN, and SEM analyses interpreted the reinforcement mechanisms. TD and BBD exhibited fair approximations, requiring 7.4% and 11.8% of the FFD experimental effort.

Development of Photoprotective Formulations: Influence of Formulation Composition on the SPF and Mechanical Properties.

The evaluation of the vehicle formulation is important during the development of sunscreens, as it influences their efficacy. In this context, the aim of the present study was to develop photoprotective formulations and evaluate the influence of the formulation components in the sun protection factor (SPF) and physical-mechanical and sensory properties of the formulations. We evaluated four sunscreens through a 22 full factorial design in terms of concentration and emulsifier type. The design of experiments (DOE) parameters were SPF, thixotropy, and work of shear. After the screening of the formulations by DOE, the SPF values, mechanical and sensory properties, and stability were evaluated. All study formulations showed non-Newtonian pseudoplastic behavior, compatible with sunscreens, and presented SPF values above 30. The factors evaluated in DOE had significant interactions for all the analyzed parameters. The concentration of the phosphate-based emulsifier influenced the SPF parameter. The work of shear was influenced by the concentration of polyglyceryl-based emulsifier. The concentration and the type of emulsifier influenced the thixotropy. Finally, effective sunscreens were developed, and the type and concentration of emulsifiers had an influence on the SPF of the formulations. In addition, the formulations chosen by DOE were stable and showed good sensory properties.

Development, stability-indicating assessment, and evaluation of influential method conditions using a full factorial design for the determination of Nintedanib esylate-related impurities.

The design of an appropriate analytical method for assessing the quality of pharmaceuticals requires a deep understanding of science, and risk evaluation approaches are appreciated. The current study discusses how a related substance method was developed for Nintedanib esylate. The best possible separation between the critical peak pairs was achieved using an X-Select charged surface hybrid Phenyl Hexyl (150 × 4.6) mm, 3.5 µm column. A mixture of water, acetonitrile, and methanol in mobile phase-A (70:20:10) and mobile phase-B (20:70:10), with 0.1% trifluoroacetic acid and 0.05% formic acid in both eluents. The set flow rate, wavelength, and injection volumes were 1.0 ml/min, 285 nm, and 5 µl, respectively, with gradient elution. The method conditions were validated as per regulatory requirements and United States Pharmacopeia general chapter < 1225 >. The correlation coefficient for all impurities from the linearity experiment was found to be > 0.999. The % relative standard deviation from the precision experiments ranged from 0.4 to 3.6. The mean %recovery from the accuracy study ranged from 92.5 to 106.5. Demonstrated the power of the stability-indicating method through degradation studies; the active drug component is more vulnerable to oxidation than other conditions. Final method conditions were further evaluated using a full-factorial design. The robust method conditions were identified using the graphical optimization from the design space.

Analytical Purity Determinations of Universal Food-Spice Curcuma longa through a QbD Validated HPLC Approach with Critical Parametric Predictors and Operable-Design's Monte Carlo Simulations: Analysis of Extracts, Forced-Degradants, and Capsules and Tablets-Based Pharmaceutical Dosage Forms.

Applications of analytical quality by design (QbD) approach for developing HPLC (High Performance Liquid Chromatography) methods for food components assays, and separations of complex natural product mixtures, are still limited. The current study developed and validated, for the first time, a stability-indicating HPLC method for simultaneous determinations of curcuminoids in Curcuma longa extracts, tablets, capsules, and curcuminoids' forced degradants under different experimental conditions. Towards separation strategy, critical method parameters (CMPs) were defined as the mobile phase solvents' percent-ratio, the pH of the mobile phase, and the stationary-phase column temperature, while the peaks resolution, retention time, and the number of theoretical plates were recognized as the critical method attributes (CMAs). Factorial experimental designs were used for method development, validation, and robustness evaluation of the procedure. The Monte Carlo simulation evaluated the developing method's operability, and that ensured the concurrent detections of curcuminoids in natural extracts, commercial-grade pharmaceutical dosage-forms, and the forced degradants of the curcuminoids in a single mixture. The optimum separations were accomplished using the mobile phase, consisting of an acetonitrile-phosphate buffer (54:46 v/v, 0.1 mM) with 1.0 mL/min flow rate, 33 °C column temperature, and 385 nm wavelength for UV (Ultra Violet) spectral detections. The method is specific, linear (R2 ≥ 0.999), precise (% RSD < 1.67%), and accurate (% recovery 98.76-99.89%), with LOD (Limit of Detection) and LOQ (Limit of Quantitation) at 0.024 and 0.075 µg/mL for the curcumin, 0.0105 µg/mL and 0.319 µg/mL for demethoxycurcumin, and 0.335 µg/mL and 1.015 µg/mL for the bisdemethoxycurcumin, respectively. The method is compatible, robust, precise, reproducible, and accurately quantifies the composition of the analyte mixture. It exemplifies the use of the QbD approach in acquiring design details for developing an improved analytical detection and quantification method.