scholarly journals Tablet Disintegration and Dispersion under In Vivo-like Hydrodynamic Conditions

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 208
Author(s):  
Jan Lenz ◽  
Frederik Fuest ◽  
Jan Henrik Finke ◽  
Heike Bunjes ◽  
Arno Kwade ◽  
...  
Keyword(s):  
Fluid Velocity ◽  
Hydrodynamic Forces ◽  
Surface Erosion ◽  
Strong Impact ◽  
The Novel ◽  
Limited Information ◽  
Hydrodynamic Conditions ◽  
Tablet Disintegration ◽  
Novel Method

Disintegration and dispersion are functional properties of tablets relevant for the desired API release. The standard disintegration test (SDT) described in different pharmacopoeias provides only limited information on these complex processes. It is considered not to be comparable to the biorelevant conditions due to the frequent occurrence of high hydrodynamic forces, among other reasons. In this study, 3D tomographic laser-induced fluorescence imaging (3D Tomo-LIF) is applied to analyse tablet disintegration and dispersion. Disintegration time (DT) and time-resolved particle size distribution in close proximity to the tablet are determined in a continuously operated flow channel, adjustable to very low fluid velocities. A case study on tablets of different porosity, which are composed of pharmaceutical polymers labelled with a fluorescent dye, a filler, and disintegrants, is presented to demonstrate the functionality and precision of the novel method. DT results from 3D Tomo-LIF are compared with results from the SDT, confirming the analytical limitations of the pharmacopoeial disintegration test. Results from the 3D Tomo-LIF method proved a strong impact of fluid velocity on disintegration and dispersion. Generally, shorter DTs were determined when cross-linked sodium carboxymethly cellulose (NaCMCXL) was used as disintegrant compared to polyvinyl polypyrrolidone (PVPP). Tablets containing Kollidon VA64 were found to disintegrate by surface erosion. The novel method provides an in-depth understanding of the functional behaviour of the tablet material, composition and structural properties under in vivo-like hydrodynamic forces regarding disintegration and the temporal progress of dispersion. We consider the 3D Tomo-LIF in vitro method to be of improved biorelevance in terms of hydrodynamic conditions in the human stomach.

Experimental Investigation on the Impact of Distorted Signal on Synthetic Jet

2016 ◽  
Vol 831 ◽  
pp. 104-111
Author(s):  
Paweł Gil
Keyword(s):  
Input Signal ◽  
Average Velocity ◽  
Fluid Velocity ◽  
Synthetic Jet ◽  
The Novel ◽  
Synthetic Jet Actuator ◽  
Negative Effect ◽  
Novel Method ◽  
Conventional Cooling ◽  
The Impact

Effective techniques for cooling electronic devices must deal with increasing heat loads associated with higher heat flux density. Many conventional cooling techniques like fan are reaching the limits of their effectiveness and shape. The novel method of heat transfer enhancement is synthetic jet. In this paper experimental results are presented. Synthetic jet actuator consist of STX 6.5 inch speaker installed in metacrylate chamber with circular orifice. The actuator was powered with signal from amplifier. The signal consist of basic sinusoidal function and THD noise added with some amplitude. The root mean square of signal voltage was constant 4V. The properties of synthetic jet were measured using constant temperature thermo-anemometer. Instantaneous velocity of air was measured in the orifice center and compared with input signal. Additional RMS and average velocity of air were measured. Measurement revealed that input signal of synthetic jet generator can contain some noise without effect on RMS and average velocity of air in the orifice. The THD less than 1% does not cause negative effect on synthetic jet fluid velocity.

Hydrodynamic Forces due to Oblique Wave and Current Loading on Untrenched Subsea Pipelines

2014 ◽  
Author(s):  
Johnathan Green ◽  
Terry Griffiths ◽  
Chris Craddock
Keyword(s):  
Oil And Gas ◽  
Standard Procedure ◽  
Fluid Velocity ◽  
Flow Characteristics ◽  
Hydrodynamic Forces ◽  
Wave Flow ◽  
Limited Information ◽  
Independence Principle ◽  
Current Loading ◽  
The University

A number of oil and gas projects encounter significant costs to achieve subsea pipeline stabilization using present methods. The standard procedure to estimate pipeline stability is to consider the worst combination of amplitude and direction of the current and waves that the pipe will undergo during its operational lifetime. To calculate the hydrodynamic forces a common approach is to consider only the component of the fluid velocity perpendicular to the pipe axis according to the independence principle. The hydrodynamic coefficients are then taken from a case where the fluid flow is perpendicular to the pipe for similar flow characteristics. A substantial amount of research has been carried out to assess the hydrodynamic forces on pipelines with the current and wave directions collinear and perpendicular to the pipe. However, only limited information is available on pipeline hydrodynamic forces for highly oblique current and wave flow. A Computational Fluid Dynamics (CFD) analysis was carried out to investigate the effect on pipeline hydrodynamic forces for highly oblique collinear and non-collinear current and wave directions. The work was carried out as part of the STABLEpipe JIP (1) (with participation by Woodside, Chevron, The University of Western Australia, and Wood Group Kenny) which aims to achieve a step-change improvement in the approaches to stability design, especially on mobile or erodible sea beds.

scholarly journals A novel method to allow noninvasive, longitudinal imaging of the murine immune system in vivo

Blood ◽  
2012 ◽  
Vol 119 (11) ◽  
pp. 2545-2551 ◽  
Author(s):  
Vivienne B. Gibson ◽  
Robert A. Benson ◽  
Karen J. Bryson ◽  
Iain B. McInnes ◽  
Catherine M. Rush ◽  
...  
Keyword(s):  
Immune Responses ◽  
In Vivo Imaging ◽  
The Novel ◽  
Novel Approach ◽  
Mouse Ear ◽  
Novel Method ◽  
Longitudinal Imaging ◽  
Secondary Lymphoid Organs ◽  
To Receive

Abstract In vivo imaging has revolutionized understanding of the spatiotemporal complexity that subserves the generation of successful effector and regulatory immune responses. Until now, invasive surgery has been required for microscopic access to lymph nodes (LNs), making repeated imaging of the same animal impractical and potentially affecting lymphocyte behavior. To allow longitudinal in vivo imaging, we conceived the novel approach of transplanting LNs into the mouse ear pinna. Transplanted LNs maintain the structural and cellular organization of conventional secondary lymphoid organs. They participate in lymphocyte recirculation and exhibit the capacity to receive and respond to local antigenic challenge. The same LN could be repeatedly imaged through time without the requirement for surgical exposure, and the dynamic behavior of the cells within the transplanted LN could be characterized. Crucially, the use of blood vessels as fiducial markers also allowed precise re-registration of the same regions for longitudinal imaging. Thus, we provide the first demonstration of a method for repeated, noninvasive, in vivo imaging of lymphocyte behavior.

A Novel Cell-Loading Method into Porous β-TCP Blocks

2006 ◽  
Vol 309-311 ◽  
pp. 993-996
Author(s):  
Ichiro Torigoe ◽  
Shinichi Sotome ◽  
A. Tsuchiya ◽  
Kenichi Shinomiya
Keyword(s):  
Bone Formation ◽  
The Novel ◽  
Cell Loading ◽  
Pressure Method ◽  
Loading Method ◽  
Loading Efficiency ◽  
Novel Method ◽  
Loading Methods ◽  
In Vivo Bone Formation

In the field of bone tissue engineering using cells combined with scaffolds, it is important to efficiently load cells into porous scaffolds. We devised a novel cell-loading method into porous beta-tricalcium phosphate (β-TCP) blocks. In this study, we compared this method with two conventional cell-loading methods in terms of cell-loading efficiency and in vivo bone formation capability. Bone marrow stromal cells (BMSCs) were obtained from the femurs of Fisher rats. After about 10 days of culture, BMSCs were harvested and suspended in the plasma of the Fisher rats at a concentration of 2×106 cells/ml. This cell suspension was loaded into porous β-TCP cubes (5×5×5mm) by using three loading methods: a soaking method, a post low-pressure method and a pre low-pressure method (the novel method). These β-TCP cubes were cross-sectioned and stained with toluidine blue and cell-counted. Cell-loading efficiency was significantly higher when using the novel methods. For the study of in vivo bone formation capability, nearly confluent BMSCs were exposed in an osteogenic medium supplemented with 10-7 M dexamethasone, 50µg/ml L-ascorbic acid phosphate and 10mM β-glycerophosphate for 4 days. These osteogenic cells were harvested and suspended in the plasma of the Fisher rats at a concentration of 2×106 cells/ml. This cell suspension was loaded into porous β-TCP cubes (5×5×5mm) by using the three cell-loading methods. Immediately, these β-TCP cubes were implanted at subcutaneous sites in the backs of 7-week-old male Fisher rats and harvested at postoperative 3 and 6 weeks. After cross-sectioning, these sections were stained with hematoxylin and eosin, and the new bone formation area was quantified. Consistent with cell-loading efficiency, in vivo bone formation capability was significantly higher in the novel method at postoperative 6 weeks. We showed the usefulness of the novel cell-loading method in bone tissue engineering.

Uptake, Internalization and Degradation of the Novel Plasminogen Activator Reteplase (BM 06.022) in the Rat

1995 ◽  
Vol 74 (06) ◽  
pp. 1501-1510 ◽  
Author(s):  
J Kuiper ◽  
H van de Bilt ◽  
U Martin ◽  
Th J C van Berkel
Keyword(s):  
Plasminogen Activator ◽  
Liver Cells ◽  
The Novel ◽  
Uptake Mechanism ◽  
Liver Uptake ◽  
Lysosomal Compartment ◽  
Β Phase ◽  
Α Phase ◽  
Parenchymal Liver

SummaryThe catabolism of the novel plasminogen activator reteplase (BM 06.022) was described. For this purpose BM 06.022 was radiolabelled with l25I or with the accumulating label l25I-tyramine cellobiose (l25I-TC).BM 06.022 was injected at a pharmacological dose of 380 μg/kg b.w. and it was cleared from the plasma in a biphasic manner with a half-life of about 1 min in the α-phase and t1/2of 20-28 min in the β-phase. 28% and 72% of the injected dose was cleared in the α-phase and β-phase, respectively. Initially liver, kidneys, skin, bones, lungs, spleen, and muscles contributed mainly to the plasma clearance. Only liver and the kidneys, however, were responsible for the uptake and subsequent degradation of BM 06.022 and contributed for 75% to the catabolism of BM 06.022. BM 06.022 was degraded in the lysosomal compartment of both organs. Parenchymal liver cells were responsible for 70% of the liver uptake of BM 06.022. BM 06.022 associated rapidly to isolated rat parenchymal liver cells and was subsequently degraded in the lysosomal compartment of these cells. BM 06.022 bound with low-affinity to the parenchymal liver cells (550 nM) and the binding of BM 06.022 could be displaced by t-PA (IC50 5.6 nM), indicating that the low-density lipoprotein receptor-related protein (LRP) could be involved in the binding of BM 06.022. GST-RAP, which is an inhibitor of LRP, could in vivo significantly inhibit the uptake of BM 06.022 in the liver.It is concluded that BM 06.022 is metabolized primarily in the liver and the kidneys. These organs take up and degrade BM 06.022 in the lysosomes. The uptake mechanism of BM 06.022 in the kidneys is unknown, while LRP is responsible for a low-affinity binding and uptake of BM 06.022 in parenchymal liver cells.

A novel method for the determination of linting propensity of paper

TAPPI Journal ◽  
2012 ◽  
Vol 11 (10) ◽  
pp. 9-17
Author(s):  
ALESSANDRA GERLI ◽  
LEENDERT C. EIGENBROOD
Keyword(s):  
Ash Content ◽  
The Novel ◽  
Offset Printing ◽  
Excellent Correlation ◽  
End Conditions ◽  
Bottom Side ◽  
Novel Method ◽  
Total Fraction

A novel method was developed for the determination of linting propensity of paper based on printing with an IGT printability tester and image analysis of the printed strips. On average, the total fraction of the surface removed as lint during printing is 0.01%-0.1%. This value is lower than those reported in most laboratory printing tests, and more representative of commercial offset printing applications. Newsprint paper produced on a roll/blade former machine was evaluated for linting propensity using the novel method and also printed on a commercial coldset offset press. Laboratory and commercial printing results matched well, showing that linting was higher for the bottom side of paper than for the top side, and that linting could be reduced on both sides by application of a dry-strength additive. In a second case study, varying wet-end conditions were used on a hybrid former machine to produce four paper reels, with the goal of matching the low linting propensity of the paper produced on a machine with gap former configuration. We found that the retention program, by improving fiber fines retention, substantially reduced the linting propensity of the paper produced on the hybrid former machine. The papers were also printed on a commercial coldset offset press. An excellent correlation was found between the total lint area removed from the bottom side of the paper samples during laboratory printing and lint collected on halftone areas of the first upper printing unit after 45000 copies. Finally, the method was applied to determine the linting propensity of highly filled supercalendered paper produced on a hybrid former machine. In this case, the linting propensity of the bottom side of paper correlated with its ash content.

scholarly journals A Novel Method to Predict Drug-Target Interactions Based on Large-Scale Graph Representation Learning

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2111
Author(s):  
Bo-Wei Zhao ◽  
Zhu-Hong You ◽  
Lun Hu ◽  
Zhen-Hao Guo ◽  
Lei Wang ◽  
...  
Keyword(s):  
Drug Target ◽  
Large Scale ◽  
Computational Models ◽  
Structural Information ◽  
Characteristic Curve ◽  
Representation Learning ◽  
Graph Representation ◽  
Convolutional Network ◽  
Novel Method

Identification of drug-target interactions (DTIs) is a significant step in the drug discovery or repositioning process. Compared with the time-consuming and labor-intensive in vivo experimental methods, the computational models can provide high-quality DTI candidates in an instant. In this study, we propose a novel method called LGDTI to predict DTIs based on large-scale graph representation learning. LGDTI can capture the local and global structural information of the graph. Specifically, the first-order neighbor information of nodes can be aggregated by the graph convolutional network (GCN); on the other hand, the high-order neighbor information of nodes can be learned by the graph embedding method called DeepWalk. Finally, the two kinds of feature are fed into the random forest classifier to train and predict potential DTIs. The results show that our method obtained area under the receiver operating characteristic curve (AUROC) of 0.9455 and area under the precision-recall curve (AUPR) of 0.9491 under 5-fold cross-validation. Moreover, we compare the presented method with some existing state-of-the-art methods. These results imply that LGDTI can efficiently and robustly capture undiscovered DTIs. Moreover, the proposed model is expected to bring new inspiration and provide novel perspectives to relevant researchers.

scholarly journals The pharmacokinetics of [18F]UCB-H revisited in the healthy non-human primate brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sébastien Goutal ◽  
Martine Guillermier ◽  
Guillaume Becker ◽  
Mylène Gaudin ◽  
Yann Bramoullé ◽  
...  
Keyword(s):  
Slow Component ◽  
Specific Binding ◽  
Compartment Model ◽  
Brain Regions ◽  
Volume Of Distribution ◽  
Pharmacokinetic Data ◽  
Limited Information ◽  
Positron Emission ◽  
Human Primate

Abstract Background Positron Emission Tomography (PET) imaging of the Synaptic Vesicle glycoprotein (SV) 2A is a new tool to quantify synaptic density. [18F]UCB-H was one of the first promising SV2A-ligands to be labelled and used in vivo in rodent and human, while limited information on its pharmacokinetic properties is available in the non-human primate. Here, we evaluate the reliability of the three most commonly used modelling approaches for [18F]UCB-H in the non-human cynomolgus primate, adding the coupled fit of the non-displaceable distribution volume (VND) as an alternative approach to improve unstable fit. The results are discussed in the light of the current state of SV2A PET ligands. Results [18F]UCB-H pharmacokinetic data was optimally fitted with a two-compartment model (2TCM), although the model did not always converge (large total volume of distribution (VT) or large uncertainty of the estimate). 2TCM with coupled fit K1/k2 across brain regions stabilized the quantification, and confirmed a lower specific signal of [18F]UCB-H compared to the newest SV2A-ligands. However, the measures of VND and the influx parameter (K1) are similar to what has been reported for other SV2A ligands. These data were reinforced by displacement studies using [19F]UCB-H, demonstrating only 50% displacement of the total [18F]UCB-H signal at maximal occupancy of SV2A. As previously demonstrated in clinical studies, the graphical method of Logan provided a more robust estimate of VT with only a small bias compared to 2TCM. Conclusions Modeling issues with a 2TCM due to a slow component have previously been reported for other SV2A ligands with low specific binding, or after blocking of specific binding. As all SV2A ligands share chemical structural similarities, we hypothesize that this slow binding component is common for all SV2A ligands, but only hampers quantification when specific binding is low.

scholarly journals REMAXINT: a two-mode clustering-based method for statistical inference on two-way interaction

2021 ◽  
Author(s):  
Zaheer Ahmed ◽  
Alberto Cassese ◽  
Gerard van Breukelen ◽  
Jan Schepers
Keyword(s):  
Null Hypothesis ◽  
Type I Error ◽  
Type I ◽  
The Novel ◽  
Simulation Studies ◽  
Test Statistic ◽  
Clustering Model ◽  
Novel Method ◽  
Main Effects ◽  
Empirical Case Studies

AbstractWe present a novel method, REMAXINT, that captures the gist of two-way interaction in row by column (i.e., two-mode) data, with one observation per cell. REMAXINT is a probabilistic two-mode clustering model that yields two-mode partitions with maximal interaction between row and column clusters. For estimation of the parameters of REMAXINT, we maximize a conditional classification likelihood in which the random row (or column) main effects are conditioned out. For testing the null hypothesis of no interaction between row and column clusters, we propose a $$max-F$$ m a x - F test statistic and discuss its properties. We develop a Monte Carlo approach to obtain its sampling distribution under the null hypothesis. We evaluate the performance of the method through simulation studies. Specifically, for selected values of data size and (true) numbers of clusters, we obtain critical values of the $$max-F$$ m a x - F statistic, determine empirical Type I error rate of the proposed inferential procedure and study its power to reject the null hypothesis. Next, we show that the novel method is useful in a variety of applications by presenting two empirical case studies and end with some concluding remarks.

scholarly journals Characterization of the SARS-CoV-2 coronavirus X4-like accessory protein

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Olanrewaju Ayodeji Durojaye ◽  
Nkwachukwu Oziamara Okoro ◽  
Arome Solomon Odiba
Keyword(s):  
Rapid Development ◽  
Protein A ◽  
The Novel ◽  
Quality Model ◽  
A Value ◽  
Model Protein ◽  
Novel Coronavirus ◽  
Global Threat

Abstract Background The novel coronavirus SARS-CoV-2 is currently a global threat to health and economies. Therapeutics and vaccines are in rapid development; however, none of these therapeutics are considered as absolute cure, and the potential to mutate makes it necessary to find therapeutics that target a highly conserved regions of the viral structure. Results In this study, we characterized an essential but poorly understood coronavirus accessory X4 protein, a core and stable component of the SARS-CoV family. Sequence analysis shows a conserved ~ 90% identity between the SARS-CoV-2 and previously characterized X4 protein in the database. QMEAN Z score of the model protein shows a value of around 0.5, within the acceptable range 0–1. A MolProbity score of 2.96 was obtained for the model protein and indicates a good quality model. The model has Ramachandran values of φ = − 57o and ψ = − 47o for α-helices and values of φ = − 130o and ψ = + 140o for twisted sheets. Conclusions The protein data obtained from this study provides robust information for further in vitro and in vivo experiment, targeted at devising therapeutics against the virus. Phylogenetic analysis further supports previous evidence that the SARS-CoV-2 is positioned with the SL-CoVZC45, BtRs-BetaCoV/YN2018B and the RS4231 Bat SARS-like corona viruses.

Sign in / Sign up

Export Citation Format

Share Document