Batch Uniformity Research Articles

Homogeneous Heat Transfer During Freeze-Drying Using Cyclic Olefin Polymer Vials

In pharmaceutical freeze-drying processes, batch homogeneity is an important quality attribute. In this context, the edge-vial-effect is a challenging phenomenon. Shortly, this effect describes that vials at the edges of the shelf dry faster and at a higher temperature compared to vials in the middle of the shelf. Studies by Ehlers et al. revealed that this effect mainly origins from the number of neighbor vials cooling each other, which is reduced for vials in corners and edges compared to vials in the middle. Due to the reduced heat transfer in cyclic olefin polymer (COP) vials, the adverse edge-vial-effect should be greatly reduced allowing a better batch uniformity. In this focused study, glass and COP vials are compared regarding this effect on a fully loaded shelf. A reference experiment with vials placed at distance using a specially designed frame is presented as well.

Basic characteristics of Vision badge and its performance as an eye lens dosimeter for endoscopists

Vision badge is an eye lens dosimeter to measure H p(3). This study aimed to evaluate the basic characteristics of the Vision badge and its performance as an eye lens dosimeter for endoscopists by phantom study. Energy dependence was evaluated by changing the tube voltage to 50 kV (effective energy of 27.9 keV), 80 kV (32.2 keV), and 120 kV (38.7 keV). Dose linearity was evaluated by changing the number of irradiation to 1, 5, and 40 times, which corresponded to 0.53, 5.32, and 21.4 mGy. Batch uniformity was evaluated by calculating the coefficient of variation of H p(3) obtained from 10 Vision badges. Angular dependence was evaluated at 0° (perpendicular to the incident direction of x-rays), 30°, 60°, 75°, and 90°. The Vision badge and optically stimulated luminescence (OSL) dosimeter were attached to the inside of the radioprotective glasses, worn on the endoscopist phantom, and the H p(3) obtained from both dosimeters were compared. The H p(3) obtained from the Vision badge with 38.7 keV was 3.8% higher than that with 27.9 keV. The Vision badge showed excellent linearity (R 2 = 1.00) with the air kerma up to 21.4 mGy. The coefficient of variation of the H p(3) for 10 Vision badges was 3.47%. The relative dose of the Vision badge decreased as the angle increased up to 75°, but increased at 90°. The H p(3) obtained by the OSL dosimeter and the Vision badge were decreased as the endoscopist phantom was turned away from the patient phantom. The H p(3) that was obtained by the Vision badge was 35.5%–55.0% less than that obtained by the nanoDot. In conclusion, the Vision badge showed specific angular dependence due to its shape, but satisfactory basic properties were exhibited for all characteristics. In phantom study, the Vision badge showed generally similar trends with the OSL dosimeter.

Rapid, non-destructive prediction of coconut composition for sustainable UHT milk production via near-infrared spectroscopy

Near-infrared (NIR) spectroscopy is a promising new technology for revolutionizing quality control and optimization in the UHT coconut milk industry. The effectiveness of NIR spectroscopy in evaluating grated coconut quality throughout the UHT coconut milk production process was thoroughly examined in this investigation. Using a partial least squares (PLS) model, the study successfully demonstrated the ability of NIR spectroscopy to accurately predict the levels of moisture, fat, protein, and pH in grated coconut. The PLS model exhibited strong correlation coefficients in calibration exceeding 0.970 and impressive ratios of performance to deviation values ranging from 3.70 to 11.75, indicating its exceptional predictive capacity. These findings underscore the remarkable potential of NIR spectroscopy in evaluating grated coconut quality throughout the UHT coconut milk production process. By harnessing the power of NIR technology, it becomes possible to consistently produce high-quality coconut milk, optimize processing conditions, ensure batch uniformity, and reduce costs by eliminating destructive testing. NIR spectroscopy is a novel and non-invasive technology for evaluating grated coconut quality in the UHT coconut milk production process, presenting an unparalleled opportunity to advance the state-of-the-art in quality control and process optimization, ultimately leading to the production of superior coconut milk products.

Recent advances in batch production of transfer-free graphene.

Large-area transfer-free graphene films prepared via chemical vapor deposition have proved appealing for various applications, with exciting examples in electronics, photonics, and optoelectronics. To achieve their commercialisation, batch production is a prerequisite. Nevertheless, the prevailing scalable synthesis strategies that have been reported are still obstructed by production inefficiencies and non-uniformity. There has also been a lack of reviews in this realm. We present herein a comprehensive and timely summary of recent advances in the batch production of transfer-free graphene. Primary issues and promising approaches for improving the graphene growth rate are first addressed, followed by a discussion of the strategies to guarantee in-plane and batch uniformity for graphene grown on planar plates and wafer-scale substrates, with the design of the target equipment to meet productivity requirements. Finally, potential research directions are outlined, aiming to offer insights into guiding the scalable production of transfer-free graphene.

Exploring the Self‐Cleaning Facets of Fluorinated Graphene Nanoarchitectonics: Progress and Perspectives

AbstractThe development of graphene nanoarchitectonics, including their synthesis, surface modification, interfaces, conductivity and porosity, has moved forward rapidly and attracted attention from interdisciplinary research fields. Fluorinated graphene (FG), a rising star and a fascinating member of graphene family has been identified as a promising material for multiple applications, such as sensors, optics, catalysis and self‐cleaning technologies. In this review, we highlight the important aspects of FG pertinent to physiochemical stability and self‐cleaning technologies. We discuss the precise functionalization of FG surfaces with organic functionalities, which are promising for creating high‐performance graphene derivatives. Also, by utilizing the reactivity of few‐layered FG nanosheets, it is possible to develop coatings based on dispersions of functionalized FG inks coupled with porous solids and tubular nanomaterials with super‐wetting functions. The functional groups of the resultant hybrids are connected to innovative substrates including meshes and macroporous sponges that can be useful for super‐wetting containers and oleophilic sorbents. Furthermore, we discuss hydrophobic FG‐porphyrin hybrids with metal coordination and hydrophobicity dependent photoluminescence. Finally, the self‐cleaning action and anti‐corrosion features of FG hybrids are explored, with potential applications in triboelectric nanogenerators and water harvesting. Future development of these materials should focus on new designs, porosity control, batch uniformity, durable self‐cleaning membranes, smart textiles, eco‐compatible coatings and disposability.

Exploring Different Carbon Allotrope Thermoplastic Composites for Electrochemical Sensing

Composite electrodes are an effective and cheap way to utilize a wide range of carbon materials to make electrodes. More recently, thermoplastics have been widely used as the binder to make carbon composite electrodes, as varying fabrication approaches, such as three-dimensional (3D) printing, can make highly reproducible electrodes. However, there is a clear need to understand how the electrochemical performance of different carbon allotrope materials varies when made into sensors. We accessed poly(lactic acid) (PLA) thermoplastic filaments containing carbon black, graphite, graphene, multiwall carbon nanotube (MWCNT), and carbon fiber using various electrochemical techniques. Graphite/PLA and graphene/PLA electrodes showed the best electron transfer kinetics. Graphene/PLA electrodes had the greatest sensitivity and lowest limit of detection for the measurement of serotonin. CB/PLA was least prone to electrode fouling from oxidative by-product generated from the oxidation of serotonin. 3D printing was used to make various carbon allotrope materials into complex shapes to evaluate the batch uniformity of the printed parts. Of all the materials explored, CB/PLA had the best resolution and batch uniformity when compared with PLA. Overall, our study highlights that the type of carbon allotrope has as much influence as the amount of carbon on the electrochemical performance of carbon thermoplastic electrodes. These findings will provide significant guidance on the appropriate choice of carbon thermoplastic composite materials when designing electrodes for a wide range of applications.

Evaluation of a New Real-Time Dosimeter Sensor for Interventional Radiology Staff.

In 2011, the International Commission on Radiological Protection (ICRP) recommended a significant reduction in the lens-equivalent radiation dose limit, thus from an average of 150 to 20 mSv/year over 5 years. In recent years, the occupational dose has been rising with the increased sophistication of interventional radiology (IVR); management of IVR staff radiation doses has become more important, making real-time radiation monitoring of such staff desirable. Recently, the i3 real-time occupational exposure monitoring system (based on RaySafeTM) has replaced the conventional i2 system. Here, we compared the i2 and i3 systems in terms of sensitivity (batch uniformity), tube-voltage dependency, dose linearity, dose-rate dependency, and angle dependency. The sensitivity difference (batch uniformity) was approximately 5%, and the tube-voltage dependency was <±20% between 50 and 110 kV. Dose linearity was good (R2 = 1.00); a slight dose-rate dependency (~20%) was evident at very high dose rates (250 mGy/h). The i3 dosimeter showed better performance for the lower radiation detection limit compared with the i2 system. The horizontal and vertical angle dependencies of i3 were superior to those of i2. Thus, i3 sensitivity was higher over a wider angle range compared with i2, aiding the measurement of scattered radiation. Unlike the i2 sensor, the influence of backscattered radiation (i.e., radiation from an angle of 180°) was negligible. Therefore, the i3 system may be more appropriate in areas affected by backscatter. In the future, i3 will facilitate real-time dosimetry and dose management during IVR and other applications.

Dietary Euterpe oleracea Essential Oil, the Amazon Açaí, as Feed Additive to Amazonian Ornamental Fish, during Post-Larvae Growing Stage: A Preliminary Study

The present study aimed to evaluate the growth performance, batch uniformity, and survival rate of the Amazonian ornamental fish Heros severus and Pterophyllum scalare during the post-larvae growing stage, fed with diets containing levels of Euterpe oleraceae essential oil (EOO) during 30 days. In the first experiment, 160 H. severus post-larvae were distributed in 16 aquariums (1 L), and in the second, 200 P. scalare post-larvae were randomly distributed in 20 aquariums (1 L). The experiments were carried out in a completely randomized design, with four treatments for H. severus (0.0%, 0.50%, 1.00%, and 2.00% of dietary EOO) and five treatments for P. scalare (0.0%, 0.5%, 1.0%, 2.0%, and 4.0% of dietary EOO), both with four replications and dietary EOO being included in replacing soybean oil. A quadratic effect (p &lt; 0.01) was observed for the final length, length gain, specific growth rate for length, final weight, weight gain, specific growth rate for weight, and batch uniformity for weight for both fish species. As for ornamental fish larviculture, survival rate and batch uniformity are the most important parameters to be considered. For P. scalare and H. severus post-larvae, the inclusion of dietary EOO was beneficial in up to 2.48% and 0.88%, respectively.

Nano to rescue: repository of nanocarriers for targeted drug delivery to curb breast cancer.

Breast cancer is a heterogeneous disease with different intrinsic subtypes. The conventional treatment of surgical resection, chemotherapy, immunotherapy and radiotherapy has not shown significant improvement in the survival rate of breast cancer patients. The therapeutics used cause bystander toxicities deteriorating healthy tissues. The breakthroughs of nanotechnology have been a promising feat in selective targeting of tumor site thus increasing the therapeutic gain. By the application of nanoenabled carriers, nanomedicines ensure targeted delivery, stability, enhanced cellular uptake, biocompatibility and higher apoptotic efficacy. The present review focuses on breakthrough of nanoscale intervention in targeted drug delivery as novel class of therapeutics. Nanoenabled carriers like polymeric and metallic nanoparticles, dendrimers, quantum dots, liposomes, solid lipid nanoparticles, carbon nanotubes, drug-antibody conjugates and exosomes revolutionized the targeted therapeutic delivery approach. These nanoassemblies have shown additional effect of improving the solubility of drugs such as paclitaxel, reducing the dose and toxicity. The present review provides an insight on the different drug conjugates employed/investigated to curb breast cancer using nanocarrier mediated targeted drug delivery. However, identification of appropriate biomarkers to target, clearer insight of the biological processes, batch uniformity, reproducibility, nanomaterial toxicity and stabilities are the hurdles faced by nanodrugs. The potential of nano-therapeutics delivery necessitates the agglomerated efforts of research community to bridge the route of nanodrugs for scale-up, commercialization and clinical applications.

High Accuracy Real-Time Multi-Gas Identification by a Batch-Uniform Gas Sensor Array and Deep Learning Algorithm.

Semiconductor metal oxide (SMO) gas sensors are attracting great attention as next-generation environmental monitoring sensors. However, there are limitations to the actual application of SMO gas sensors due to their low selectivity. Although the electronic nose (E-nose) systems based on a sensor array are regarded as a solution for the selectivity issue, poor accuracy caused by the nonuniformity of the fabricated gas sensors and difficulty of real-time gas detection have yet to be resolved. In this study, these problems have been solved by fabricating uniform gas sensor arrays and applying the deep learning algorithm to the data from the sensor arrays. Nanocolumnar films of metal oxides (SnO2, In2O3, WO3, and CuO) with a high batch uniformity deposited through glancing angle deposition were used as the sensing materials. The convolutional neural network (CNN) using the input data as a matrix form was adopted as a learning algorithm, which could conduct pattern recognition of the sensor responses. Finally, real-time selective gas detection for CO, NH3, NO2, CH4, and acetone (C3H6O) gas was achieved (minimum response time of 1, 8, 5, 19, and 2 s, respectively) with an accuracy of 98% by applying preprocessed response data to the CNN.

Efeitos da fibra dietética extrusada na alimentação de matrizes suínas em gestação / Effects of extruded dietary fiber in the diet of gestating sows

This work was based on the experiment in which forty-four newly weaned pig matrices with the same birth order and age were used, equally distributed in two experimental groups where they received two different treatments, with and without an increase of 15% of extruded fiber along gestational period. Collections and analysis of zootechnical data were performed at 40, 65, 87, 107 days of gestation, and after 21 days of piglets. The main objectives proposed were achieved with satisfaction, which were to maintain the batch uniformity (body score close to 3), ideal fecal score, reduction of stereotypes caused by the sensation of hunger, and increase in the number of piglets born alive and consequently weaned. The swine matrices, besides having been submitted to the animal welfare precepts, characterizing a healthier creation, still presented an increase of 1.95 more piglets per parturition.

Recommended Best Practices for Lyophilization Validation 2021 Part II: Process Qualification and Continued Process Verification

This work describes the lyophilization process validation and consists of two parts. Part one (Part I: Process Design and Modeling) focuses on the process design and is described in the previous paper, while the current paper is devoted to process qualification and continued process verification. The goal of the study is to show the cutting edge of lyophilization validation based on the integrated community-based opinion and the industrial perspective. This study presents best practices for batch size determination and includes the effect of batch size on drying time, process parameters selection strategies, and batch size overage to compensate for losses during production. It also includes sampling strategies to demonstrate batch uniformity as well as the use of statistical models to ensure adequate sampling. Based on the LyoHUB member organizations survey, the best practices in determining the number of PPQ runs are developed including the bracketing approach with minimum and maximum loads. Standard practice around CQA and CPP selection is outlined and shows the advantages of using control charts and run charts for process trending and quality control. The case studies demonstrating the validation strategy for monoclonal antibody and the impact of the loading process on the lyophilization cycle and product quality as well as the special case of lyophilization for dual-chamber cartridge system are chosen to illustrate the process validation. The standard practices in the validation of the lyophilization process, special lyophilization processes, and their impact on the validation strategy are discussed.Graphical

A brief review on pharmaceutical dissolution - interlinking the aspects of science and regulation.

Dissolution is a multistep process between the affinity of the solute and the solvent by which a solid substance interacts among the heterogeneous phases of solute -solute, solvent-solvent and the solute-solvent interface to yield a solution. In pharmaceutical industry dissolution testing of solid dosage form gives a signal of the operability of the dosage form in biological system. The rate of absorption is partially or completely controlled by the dissolution of drug from its dosage forms in the gastrointestinal tract. This vital quality control aspects also ensures batch to batch uniformity in drug release, bioavailability, and to develop efficacious therapeutic dosage forms. It also ensures to evaluate critical biopharmaceutical parameters of the dosage forms. Hence the study of dissolution is an interplay between the science and the development of regulatory profile of a dosage form for quality control aspects. The present review focuses on the science, theories, factors relevant to in vitro dissolution, and therefore the role of it’s in the pharmaceutical regulation.

Analytical method development and validation for simultaneous estimation of monoammonium glycyrrhizinate and sennoside-B in polyherbal laxative tablet using RP-HPLC

BackgroundStandardization of polyherbal medicine though being the need of the hour is a toilsome task. Among the various methods employed for quality control and standardization of polyherbal medicine, phytochemical profiling is of utmost importance as it signifies the quality as well as efficacy of the medicine. The work was aimed to develop and validate a simple, quick, and accurate RP-HPLC technique for simultaneous assessment of monoammonium glycyrrhizinate and sennoside-B in a polyherbal laxative tablet. The phytomarkers were effectively quantified by RP-HPLC system on C18 analytical column using gradient mobile phase consisting of phosphate buffer to acetonitrile with the detector wavelength set at 254 nm. This developed method was validated by determination of parameters like accuracy, linearity, precision, limit of detection, and quantification as well as robustness according to ICH guidelines.ResultsCalibration curve of both phytomarkers showed excellent linear correlation coefficients. LOD and LOQ were also calculated by equation. Precision studies were carried out using intra-day and inter-day intervals and RSD values were found to be less than 2.00%. The method was found to be accurate, which was evident from 98.96 to 101.39% and 99.17 to 100.67% recovery of monoammonium glycyrrhizinate and sennoside-B, respectively, when the formulation was spiked with the respective phytomarkers.ConclusionThe validated method can be employed as standardization tool for herbal formulations with accuracy and precision. The developed method will assist in maintaining the good quality and batch to batch uniformity of polyherbal formulations containing Yashtimadhu, Swarnpatri, and Aragvadha as active ingredients.

An initial investigation of a wireless patient radiation dosimeter for use in interventional radiology.

Radiation exposure during interventional radiology (IR) procedures is a critical issue. We have developed a wireless real-time dosimeter for IR patients that use nontoxic phosphor (four sensors). We evaluated the basic performance parameters (such as dose linearity, batch uniformity, reproducibility, and wireless-communication conditions) of the developed system using an IR X-ray system. Further, we investigated the influence of noise from other medical equipment on our wireless real-time dosimeter in the IR X-ray room. Overall, our wireless system exhibited excellent performance in terms of uniformity, reproducibility, and linearity; moreover, the wireless communication performance was better. The developed system enabled real-time visualization of patient radiation dose, without noise contamination from other medical equipment. In addition, the wireless system can be easily installed in a location where the PC screen (display) can be readily viewed by the IR physician. Hence, we developed a wireless system that can display the patient radiation dose data in real time; the system performed satisfactorily upon application in radiation dosimetry. Therefore, our wireless system will facilitate the real-time monitoring/management of patient radiation dose during IR.

Batch synthesis of transfer-free graphene with wafer-scale uniformity

Scalable synthesis of transfer-free graphene over insulators offers exciting opportunity for next-generation electronics and optoelectronics. However, rational design of synthetic protocols to harvest wafer-scale production of directly grown graphene still remains a daunting challenge. Herein we explore a batch synthesis of large-area graphene with wafer-scale uniformity by virtue of direct chemical vapor deposition (CVD) on quartz. Such a controllable CVD approach allows to synthesize 30 pieces of 4-inch graphene wafers in one batch, affording a low fluctuation of optical and electrical properties. Computational fluid dynamics simulations reveal the mechanism of uniform growth, indicating thermal field and confined flow field play leading roles in attaining the batch uniformity. The resulting wafer-scale graphene enables the direct utilization as key components in optical elements. Our method is applicable to other types of insulating substrates (e.g., sapphire, SiO2/Si, Si3N4), which may open a new avenue for direct manufacture of graphene wafers in an economic fashion.

Horseshoe Crab Aquaculture as a Sustainable Endotoxin Testing Source

Horseshoe crab (HSC) hemolymph is the source of Limulus amebocyte lysate (LAL), a critical component in sterility testing that ensures drug and medical device safety for millions of patients every year. Wild HSC populations have been declining as a result of use as whelk and eel bait, and largely due to capture and bleeding for hemolymph, primarily while spawning, thus posing significant biomedical supply and species viability risks. We investigated aquaculture as an alternative to current practices as a means to foster conservation by establishing a sustainable endotoxin testing resource. We found HSC aquaculture to be practicable based on routine hemolymph harvesting, batch uniformity, and LAL quality, while safeguarding animal wellbeing. Achieving sustainable LAL production could satisfy industry needs for several years with a fraction of one year’s current capture with low-impact, year-round harvesting of a finite cohort. Sustainable supplies of LAL could also be adapted to address daunting trends in septicemia and antimicrobial resistance. LAL is uniquely sensitive and specific for gram-negative bacteria, which represent 70-80% of pathogens typically attributed to sepsis. Early diagnosis of bacterial infection and timely antibiotic therapy can reduce patient mortality. However, erratic results associated with interfering substances plagued efforts to adapt LAL for clinical use in the past. Our efforts to develop new methods have yielded a promising LAL screening technique to detect a gram-negative bacteria and endotoxins in human blood.

Performance of the DOSIRIS™ eye lens dosimeter

Monitoring and protecting of occupational eye doses in interventional radiology (IR) are very important matters. DOSIRIS™ is the useful solution to estimate the 3 mm dose-equivalent (Hp(3)), and it can be worn behind lead glasses. And DOSIRIS™, adjustable according to 3 axes, it is ideally placed as close to the eye and in contact with the skin. So, DOSIRIS™ will be suitable eye lens dosimeter. However, the fundamental characteristics of the DOSIRIS™ in the diagnostic x-ray energy domain (including that of IR x-ray systems) remain unclear. Here, we evaluated the performance of the dosimeter in that energy range. As a result, the DOSIRIS™ has good fundamental characteristics (batch uniformity, dose linearity, energy dependence, and angular dependence) in the diagnostic x-ray energy domain. We conclude that the DOSIRIS™ has satisfactory basic performance for occupational eye dosimetry in diagnostic x-ray energy settings (including IR x-ray systems).

Optimal feeding frequency for Heros severus (Heckel, 1840), an Amazon ornamental fish

ABSTRACT The influence of feeding frequency on growth performance, batch uniformity, and survival rate of severum (Heros severus) larvae and juveniles was investigated in two experiments. In the first, 200 five-day-old severum larvae with 3.20±0.31 mg and 6.20±0.39 mm were randomly distributed into 20 aquaria (1 L) and fed 500 Artemia nauplii larvae−1 day−1 for 15 days. In the second, 120 severum juveniles, 178.19±33.59 mg and 1.82±0.09 cm, were randomly distributed into 15 aquaria (300 L) and hand-fed a commercial [...]

Gas sensors based on assembled porous graphene multilayer frameworks for DMMP detection

In this work, a structure of assembled porous graphene multilayer frameworks was demonstrated to endow the resultant sensing devices with batch uniformity, good response, sensitivity, and selectivity.