Manufacturing Conditions Research Articles

Continuous manufacturing of pharmaceutical products: A density-insensitive near infrared method for the in-line monitoring of continuous powder streams

Near infrared (NIR) spectroscopy is a valuable analytical technique for monitoring chemical composition of powder blends in continuous pharmaceutical processes. However, the variation in density captured by NIR during spectral collection of dynamic powder streams at different flow rates often reduces the performance and robustness of NIR models. To overcome this challenge, quantitative NIR measurements are commonly collected across all potential manufacturing conditions, including multiple flow rates to account for the physical variations. The utility of this approach is limited by the considerable quantity of resources required to run and analyze an extensive calibration design at variable flow rates in a continuous manufacturing (CM) process. It is hypothesized that the primary variation introduced to NIR spectra from changing flow rates is a change in the density of the powder from which NIR spectra are collected. In this work, powder stream density was used as an efficient surrogate for flow rate in developing a quantitative NIR method with enhanced robustness against process rate variation. A density design space of two process parameters was generated to determine the conditions required to encompass the apparent density and spectral variance from increases in process rate. This apparent density variance was included in calibration at a constant low flow rate to enable the development of a density-insensitive NIR quantitative model with limited consumption of materials. The density-insensitive NIR model demonstrated comparable prediction performance and flow rate robustness to a traditional NIR model including flow rate variation (“gold standard” model) when applied to monitoring drug content in continuous runs at varying flow rates. The proposed platform for the development of in-line density-insensitive NIR methods is expected to facilitate robust analytical model performance across variable continuous manufacturing production scales while improving the material efficiency over traditional robust modeling approaches for calibration development.

Experiment and Numerical Studies of Convection Heat Transfer around a Rotating Hand-Shaped Former

Forced convective heat transfer around a rotating hand-shaped former was numerically studied to improve the rubber-glove-curing process. The former surface was separated into eight segments for simulation. The shear stress transport turbulence model and its wall functions were employed to model the rotating hand-shaped former in the heated airflow field. The rotation rate of the former varied from 0 to 5 in the freestream. The Reynolds number ranged from 1,583 to 15,837. The simulation results were compared and well agreed with the experimental data. These results indicated that the convective heat transfer of individual sections and the entire body varied according to the aforementioned variables. The most effective rotation rate was observed for the former segments that were far from the rotation axis. The lowest convective heat transfer occurred in the middle finger, which was located on the rotation axis and was shielded by other segments. Therefore, the average Nusselt number on the middle finger was significant and derived using a novel equation. This equation was compared with the computational fluid dynamics results and exhibited an average error and correlation coefficient of 7.32% and 0.9, respectively. It can help reduce the trial-and-error method to obtain curing conditions for rubber glove manufacturing.

Effect of Powdered Cellulose Nanofiber with Different Particle Sizes on the Physical Properties of Tablets Manufactured via Direct Compression.

Direct compression is a tableting technique that involves a few steps in non-demanding manufacturing conditions. High strength and rapid disintegration of tablet formulations were previously achieved through the addition of cellulose nanofibers (CNFs), which have recently attracted attention as a high-performance biomass material. However, CNF addition results in greater variation in tablet weight and drug content, potentially due to differences in particle size between CNF and other additives. Herein, we used pulverized CNF to evaluate the effect of CNF particle size on the variation in tablet weight and drug content. Tablet formulations consisted of CNF with different particle sizes (approximately 100 µm [CNF100] and 300 µm [CNF300], at 0, 10, 30, or 50%), lactose hydrate, acetaminophen, and magnesium stearate. Ten powder formulations with different particle sizes and CNF concentrations were prepared; thereafter, the tablets were produced using a rotary tableting press with a compression force of 10 kN. The variation in weight and drug content as well as the tensile strength, friability, disintegration time, and drug dissolution of tablets were evaluated. CNF100 addition to the tablets reduced the weight and drug content variation to a greater extent than CNF300 addition. Using CNF300, we produced tablets of sufficient strength and short disintegration time. These properties were also achieved with CNF100 addition. Our findings suggest that adding CNF of small particle size to the tablet formulation can reduce the variation in weight and drug content while maintaining high strength and short disintegration time.

Characteristics and performance analysis of activated carbons derived from different precursors and activators for waste water adsorption

Domestic waste such as methylene blue from the dyeing process and detergent from laundry activities are sources of water pollution. Before being dumped into the water, this waste must be minimized. One approach that can be utilized is the adsorption method with activated carbon. To generate activated carbon with the properties required for this purpose, an appropriate precursor and manufacturing conditions must be chosen. The objective of this research is to investigate the characteristics and performance of activated carbon derived from various precursors (Petung and Santong bamboos) and activators (Ar, N2, and CO2) for detergent and methylene blue dye adsorption. The difficulty to be solved is determining the best precursor and activator for maximum methyl blue and detergent adsorption. Characterizations included FTIR, XRD, SEM, TGA, and adsorption isotherm testing. The study's findings show that activated carbons have functional groups O-H (hydroxyl), C-H (aldehydes and alkenes), C=C aromatic rings, C-H aromatic groups, and an amorphous structure. The presence of a porous and amorphous structure, as well as the C=C aromatic ring, makes activated carbons capable of absorbing methyl blue and detergent. Santong bamboo-activated carbon activated with argon has the best characteristics and adsorption capability. This activated carbon has a fixed carbon content of 76.34 %, pore volumes of 0.362 cc/g, average pore widths of 1.967 nm, pore surface area of 291.487 m2/g, bimodal pore size distribution, and methylene blue and detergent adsorption capabilities of 19.733 cc/g and 1.689 cc/g, respectively. The results obtained are on a laboratory scale, which necessitates additional research, particularly on how to create reservoirs and regenerate activated carbon simply and affordably

Shear performance of centrifugal forming hollow circular SFRC piles: Feasibility study of replacing stirrups with steel fibers

This paper aims to investigate shear performance and develop an equation for shear strength assessment of centrifugal forming hollow circular steel fiber reinforced concrete (HSFRC) piles in a practical manufacturing condition. The centrifugal forming was optimized using concrete mixes with different steel fibers. The shear performance and size effect of HSFRC and conventional hollow circular reinforced concrete (HRC) piles with/without stirrups were investigated. Results of X-ray visualization show that, after centrifugal forming, steel fibers were evenly distributed and reoriented in the circumferential direction of the piles, effectively enhancing shear performance. Even with a low steel fiber content of 0.5%, HSFRC piles achieve equivalent shear performance and less brittle behavior compared to HRC piles with shear reinforcement ratios of 0.27%. This implies that higher steel fiber contents can potentially be used to replace stirrups for a flexural failure. SFRC remarkably inhibited the size effect of HSFRC piles. Moreover, a proposed equation considering fiber orientation can better predict the shear strength of centrifugal forming HSFRC piles compared to existing equations.

Investigation of manufacturing conditions of single roll rapidly solidified ribbon for anode materials of magnesium rechargeable batteries

Investigation of manufacturing conditions of single roll rapidly solidified ribbon for anode materials of magnesium rechargeable batteries

Inactivation of Listeria monocytogenes by Hydrogen Peroxide Addition in Commercial Cheese Brines

Commercial cheese brines are used repeatedly over extended periods, potentially for years, and can be a reservoir for salt-tolerant pathogens, such as Listeria monocytogenes. The objective of this study was to determine the inactivation of L. monocytogenes in cheese brines treated with hydrogen peroxide (H2O2) (0, 50, and 100 ppm) at holding temperatures representing manufacturing conditions. In experiment one, four fresh cheese brines were prepared with 10 or 20% salt and pH 4.6 or 5.4 (2x2 design; duplicate trials). Brines were inoculated with L. monocytogenes, treated with H2O2, and stored at 10 and 15.6°C. For experiment two, seven used commercial brines (representing five cheese types, 15–30% NaCl, pH 4.5–5.5; three seasonal trials) were inoculated with L. monocytogenes or S. aureus, treated with H2O2, and stored at 12.8°C (both L. monocytogenes and S. aureus), 7.2 and 0°C (L. monocytogenes only). Each treatment was assayed on Days 0, 1, and 7 for microbial populations and residual H2O2. Data revealed that pathogen populations decreased ≤1 log in cheese brines with no hydrogen peroxide stored for 7 days, regardless of the storage temperature. In fresh brine treated with 50 or 100 ppm of H2O2, populations of L. monocytogenes were reduced to less than the detectable limit by 7 days at 10 and 15.6°C (>4 log reduction). For unfiltered used brines, H2O2 had no effect on L. monocytogenes populations in Brick J (pH 5.4, 15% NaCl) due to rapid inactivation of H2O2, likely by indigenous yeasts (∼3-log CFU/ml). For the remaining brines, the addition of 100 ppm H2O2 killed >4 log L. monocytogenes when stored at 7.2 or 12.8°C for 1 week, but only 3–4 log reduction when stored at 0°C. The addition of 50 ppm H2O2 had similar lethal effects at 12.8°C but was less effective at 7.2 or 0°C. Inactivation rates of S. aureus were similar to that of L. monocytogenes. This study confirmed that high salt, warmer temperature, and 100-ppm H2O2 accelerated the inactivation of L. monocytogenes in cheese brines. Data also suggest that the presence of catalase-positive indigenous microorganisms may neutralize the effect of H2O2.

Predictive microstructure distribution and printability maps in laser powder bed fusion for a Ni–Cu alloy

The solidification microstructure of a melt pool under additive manufacturing conditions is highly heterogeneous due to the heterogeneity in the thermal spatio-temporal fields. This work combines a finite element (FE)-based thermal model with a phase field model (PFM) to predict microstructure distribution among the process parameter span in LPBF, which is strongly controlled by local thermal histories. The segregation distribution across the parameter space can be classified into four different microstructure distribution types: (i) fully planar, (ii) bottom dendritic, (iii) top dendritic, and (iv) fully dendritic. Also, the relationship between the thermal histories (the temperature gradient (G) and the growth rate (R)) variation induced by P and V→ and the microstructure distribution is clearly analyzed in the paper. For a Ni-20 at.%Cu alloy, the predicted microstructural distribution is verified experimentally. The parameter space is further divided into homogeneous and heterogeneous regions using the predicted area fraction of cellular–dendritic segregation across the melt pools. The process map is then used to build AM parts with homogeneous microstructures, where only planar microstructure is found experimentally. This methodology will aid in the exploitation of the alloy and processing space to identify alloy-process combinations that yield microstructurally-homogeneous, defect-free parts, provided an unconditionally printable regime can be identified.

Potential of Incorporating a Functional Probiotic Encapsulant in Whipped Cream

The probiotic foods market is expanding; however, maintaining probiotics viability is challenging during manufacturing and storage conditions. In this study, a functional ingredient containing whey protein hydrolysate-encapsulated probiotics was standardized into whipped cream, followed by its characterization and storage stability study. The whipped cream was prepared under standard laboratory conditions, and the encapsulant was added at 0.1% and 1% w/w levels. The samples were further characterized through viable probiotic counts, physicochemical and microstructural analysis. Analyses were conducted in triplicates, and ANOVA was applied to differentiate between the mean values (p < 0.05). The whipped cream variant with 1% w/w encapsulant addition exhibited higher viability of Lactobacillus acidophilus ATCC4356 (LA5) (7.38 ± 0.26 log10CFU/g) and Bifidobacterium animalis ssp. Lactis ATCC27536 (BB12) (7.25 ± 0.56 log10CFU/g) along with enhanced physicochemical properties as compared to the LA5 (6.53 ± 0.45 log10CFU/g) and BB12 (6.41 ± 0.39 log10CFU/g) counts in the 0.1% variant. This was attributed to the thicker and uniform encapsulant deposition at the O/W interface observed in micro-images. The storage stability results did not show a substantial difference in viability for encapsulated probiotics compared to the control. The encapsulant also maintained the 1:1 ratio of LA5 and BB12. Thus, a value-added range of dairy products could be introduced with enhanced physicochemical attributes.

On the Influence of Scattered Errors over Full-Field Receptances in the Rayleigh Integral Approximation of Sound Radiation from a Vibrating Plate

Spatially dense operative deflection shapes and receptances, acquired in broad frequency bands, increase the detail in the spatial and frequency domains of the responses of parts in actual dynamic loading, manufacturing and mounting conditions. This work remarks the potential benefits of greater spatial resolution in the Rayleigh integral approximation of sound pressure—here reformulated to exploit the increased quality output from experiment-based optical full-field technologies in contactless structural dynamics—radiated by a vibrating surface in a broad frequency band. But in some cases the noise that is scattered over the estimated receptance maps might be heavier, or with different patterns, than expected, with potential repercussions on the sound pressure simulations that come thereof. This work covers this specific latter issue with insight over examples from experiment-based receptances of a lightweight vibrating plate. The effects of error spreading are analysed in the space and frequency domains, with special attention to the contribution of the experiment-based full-field receptance maps to the accuracy of the vibro-acoustic frequency response function maps.

A human-cyber-physical system for Operator 5.0 smart risk assessment

In the context of Industry 5.0, characterized by the human-centred transformation of manufacturing processes, assessing operator risk is crucial for ensuring workplace safety and well-being. In this respect, this paper presents the development of a human-cyber-physical system (HCPS) capable of estimating operator risk by leveraging diverse sensing data. By comprehensively analysing complex patterns and interactions among physiological, environmental, and manufacturing variables, the HCPS offers an advanced approach to operator risk assessment. Through the integration of cutting-edge sensing technologies, real-time data collection, and sophisticated analytics paradigms, the HCPS accurately identifies meaningful patterns and anomalies. It dynamically adapts to changing manufacturing conditions, generating risk profiles for operators and work processes. Timely alerts and notifications enable proactive interventions, enhancing safety measures and optimizing work processes. The HCPS empowers decision-making and supporting the well-being and productivity of operators in the Industry 5.0 paradigm, while maintaining a safe working environment. A simulated case study is reported to validate the proposed framework on a variety of industrial scenarios.

Vacuum-Assisted Die Casting Method for the Production of Filigree Textile-Reinforced Concrete Structures

Concrete is the most widely used building material today. The enormous amount used goes hand in hand with high material consumption and CO2 emissions. Thus, building with concrete must be improved, becoming part of the solution on the way to climate-friendly building. Non-metallic fibres are an alternative to corrosion-sensitive steel reinforcement, and they enable the production of filigree, high-performance, structured components with low concrete cover. This article presents an alternative manufacturing method. Our thesis was that concreting under negative air pressure conditions (APC) allows the easy production of complicated, thin-walled geometries without defects or loss of mechanical properties. We firstly present the principle of the vacuum-assisted method and its technical realization. The proof of concept included the production and laboratory tests of different specimens, casted under normal and negative APC. The fine concrete’s properties were determined in flexural and compression tests. Textile-reinforced concrete was analysed in tensile and bond tests as well as in bending trials on 2.7 m long shell elements. To summarize, it can be stated that the mechanical properties achieved were comparable, independent of the manufacturing conditions. The production quality of the shell elements was improved by concreting under negative APC. Finally, an outlook is given to further improve the method.

Shell Formulation in Soft Gelatin Capsules: Design and Characterization.

Soft gelatin capsules (SGCs)are the most widely used pharmaceutical form after tablets. The active components, active pharmaceutical ingredients (APIs), or nutrients are dissolved, dispersed, or suspended in a liquid or semisolid fill, which is covered with a gelatin shell. Several factors can modify the properties of the gelatin shell and subsequently affect their operative handling during manufacturing process and the stability of the soft gelatin capsules. Three elements appear to be crucial: the shell formulation (type and content of the different components such as gelatins-source, extraction method-plasticizers, or additives); the manufacture and storage conditions (temperature, humidity, light) as well as the interactions between fill-shell formulas. Mechanical and thermal analysis arise as straightforward but highly useful tools to monitor the properties of the gelatin shell. This review provides an updated overview on the shell formulation and design. Additionally, it presents the uses of mechanical and thermal techniques to characterize and evaluate the impact of different parameters on the gelatin behavior over the production and stability of these pharmaceutical forms. This will help to detect changes that are yet not visible by visual inspection ensuring a suitable finished product over its shelf-life.

Investigating the impact of manufacturing conditions on crack growth rate in nitrile butadiene rubber for enhanced service life – Part 01

Extended service life of components is playing an increasingly important role in society and economy. Accordingly, this also applies to elastomeric materials, which are used for example for tires, seals, and hoses. These are often exposed to cyclic loading, with crack initiation and growth playing a decisive role. Corresponding phenomena have been investigated for many years and are still not fully understood. For the fatigue behavior, the crosslinking state of the material is of particular importance. This is accompanied by various production parameters, such as processing temperature and curing time, which have been of little importance in research to date. For this reason, plain strain test specimens out of nitrile butadiene rubber (NBR) were produced by injection molding at different mold temperatures and crosslinking times in the present work. With the aid of these, the crack growth rate at different crosslinking states under cyclic loading was investigated. It has been shown that a longer crosslinking time toward fully cured specimens results in a 20% reduction in dissipated energy, with a corresponding increase of the crack growth rate by the factor of 100. Furthermore, a 20 K increase in mold temperature during manufacturing of fully cured specimens leads to a four times slower crack growth.

Exploring the Prospects of Macadamia Nutshells for Bio-Synthetic Polymer Composites: A Review.

The global production of macadamia nuts has witnessed a significant increase, resulting in the accumulation of large quantities of discarded nutshells. These nutshells possess the properties of remarkable hardness and toughness, which are comparable to those of aluminum. Incorporating natural fillers to enhance the properties of composite materials for various applications, including light duty, structural, and semi-structural purposes, is a common practice. Given their inherent hardness and toughness, macadamia nutshells present an intriguing choice as fillers, provided that the manufacturing conditions are economically viable. With the urgent need to shift toward natural fillers and reduce reliance on synthetics, exploring macadamia nutshells as components of natural fiber composites becomes imperative. This review aims to comprehensively examine the existing body of knowledge on macadamia nutshells and their bio-synthetic polymer composites, highlighting key research findings, achievements, and identifying knowledge gaps. Furthermore, the article will outline prospective areas of focus for future research endeavors in this domain, aligning with the universal goal of minimizing synthetic materials.

Turbine Blade Endwall Heat Transfer and Film Cooling Performance With Multigap Jets and Film Holes

Abstract Due to manufacturing, assembly, and operational conditions, gaps are commonly presented in the turbine components, such as platform blade-to-blade gap (slashface gap) and rim cavity platform gap (slot gap). The coolant ejected through these gaps not only limits hot mainstream gas ingestion into the disk cavity but also has the potential to provide endwall film cooling coverage. Nevertheless, the interaction of these gap flows, predesigned film hole jets, and endwall secondary flows, significantly impacts endwall heat transfer and film cooling performance and leads to a more complicated flow field near endwall. To further understand the endwall flow physics behavior in this complicated flow field, the combined effects of film hole jets and multigap leakages (slashface jet and slot jet) were experimentally studied in a transient wind tunnel with a six-blade linear cascade (nonrotating). The endwall heat transfer was measured and recorded by the IR technique at inlet average turbulence intensity (Tu) of 7.5% and an exit Mach number (Maex) of 0.4. In addition, detailed numerical predictions were also performed to discuss the flow physics near endwall and the multigap leakages behavior. Results indicated that the slashface jet is an essential contributor to endwall film cooling performance in this endwall configuration. The slashface jet delays the development of the film hole jets, leading to an enhancement of film cooling performance downstream of the film holes. Increasing the mass flow ratio of the slashface jet (MFRslashface) can prevent the high-temperature mainstream ingestion, reduce the thermal failure risks, and increase the peak of film cooling effectiveness downstream of the endwall (167% at MFRslashface = 0.5%). Due to the limitation and hindrance impacts of the disk vortex (DV), the cavity vortex (CV), and the suction side leg of the horse-shoe vortex (HV,s), the slot flow is confined to a small region downstream of the slot gap.

Оценка технико-экономической эффективности применения аддитивных технологий при изготовлении деталей космических аппаратов

The paper presents technical and economic analysis of the effectiveness of using the features and advantages of the additive selective laser melting (SLM) technology in design and manufacture of the spacecraft antenna-feeder systems (AFS) elements using specific examples of the angular waveguides and antennas manufactured at the Lavochkin Association. Main advantages of introducing the SLM technology in comparison with the use of traditional technologies are shown. They include reducing duration and cost of the product development and manufacturing processes; ability to create unique designs with new performance characteristics inaccessible to other technologies; improvement of the weight and size characteristics; increasing the spacecraft active life by improving the AFS reliability. Results of the technical and economic analysis confirm effectiveness and relevance of the SLM technology implementation in conditions of the spacecraft AFS elements small-scale manufacture at the rocket and space industry enterprises.

An atomistic investigation on the sintering behaviour of AlSi10Mg nanoparticles during the laser powder bed fusion process

The laser powder bed fusion process represents an innovative manufacturing technique within the context of Industry 4.0. This method involves creating components in a layered manner by melting or compacting together individual powder particles. The process of compacting multiple-component metal powders significantly affects the mechanical and physical characteristics of the final product. In this particular investigation, an atomistic model is constructed to gain a deeper understanding of how AlSi10Mg metal powders with multiple components fuse together. This model is employed to examine how the compacting behavior changes for AlSi10Mg particles that are 4 nm in size at varying sintering temperatures: specifically, 800 K, 950 K, and 1100 K. The growth of interparticle connections (referred to as “necks”) and the ratio of shrinkage are quantified over time as the compacting process takes place. The results of the simulations reveal that increasing the sintering temperature leads to a wider neck, expanding from 51.81 Ã… to 53.63 Ã…. Correspondingly, the shrinkage ratio also increases as the sintering temperature rises. These findings offer insights into enhancing the manufacturing conditions and material formulations for multi-component nano powders.

Molecular phenomena related to moisture uptake in amorphous solid dispersion loaded with bosentan monohydrate and copovidone

Amorphous bosentan alone lacks dissolution flux that could enhance its bioavailability. Its coamorphization with hydrophilic copovidone (1:1) enables to improve wettability and dissolution rate, but fine amorphous particles are prone to moisture uptake. Water sorbed on the surface of this amorphous solid dispersion can considerably alter its physical properties annihilating benefits of coamorphization. The gravimetric measurements of water uptake, the solid state 1H NMR spectroscopy and relaxometry enabled us to describe for the first time, phase changes initiated by hydration in amorphous bosentan systems. The properties of copovidone greatly impacted water uptake in bosentan solid dispersions. A nonlinear reduction of the Tg upon water sorption resulted in the transformation of the glassy state into the rubbery state at ambient temperature. The state diagrams were developed for optimization of manufacturing conditions, selection of suitable packaging material and storage temperature, ensuring long-term stability of amorphous bosentan products.

Sand Modified with Nanoparticles of Calcium, Aluminum, and CTAB in the Form of Layered Double Hydroxide for Removing of Amoxicillin from Groundwater

The addition of new reactive sites on the surface area of the inert sand, which are represented by layered double hydroxide nanoparticles, is the primary goal of this work, which aims to transform the sand into a reactive material. Cetyltrimethylammonium bromide (CTAB) surfactant is used in the reaction of calcium extracted from solid waste-chicken eggshells with aluminum prepared from the cheapest coagulant-alum. By separating amoxicillin from wastewater, the performance of coated sand named as "sand coated with (Ca/Al-CTAB)-LDH" was evaluated. Measurements demonstrated that pH of 12 from 8, 9, 10, 11, and 12, CTAB dosage of 0.05 g from 0, 0.03, 0.05, and 0.1 g, ratio of Ca/Al of 2 from 1, 2, 3, and 4, and mass of sand of 1 g/50 mL from 0.5, 1, 1.5, 2, and 2.5 g/50 mL are the optimal manufacturing conditions for coated sand to guarantee an antibiotic removal efficiency greater than 80. After planting the LDH nanoparticles, characterization analyses revealed that the generation of a plate-like layer composed of loosely aggregated micrometric plates had significantly altered the structure of sand. Finally, as the sorbent mass increased as well as the flow rate and inlet contaminant concentration (Co) decreased, the longevity of coated sand in the packed column significantly increased. In comparison to the Belter-Cussler-Hu and Yan models, the Thomas-BDST model provides a more accurate simulation of measured breakthrough curves.