Characterization of Effective Diffusion within Viscoelastic Fluids with Elastic Instabilities

We considered effective diffusion, characterized by magnitudes of effective diffusion coefficients, in order to quantify mass transport due to the onset and development of elastic instabilities. Effective diffusion coefficient magnitudes were determined using different analytic approaches, as they were applied to tracked visualizations of fluorescein dye front variations, as circumferential advection was imposed upon a flow environment produced using a rotating Couette flow arrangement. Effective diffusion coefficient results were provided for a range of flow shear rates, which were produced using different Couette flow rotation speeds and two different flow environment fluid depths. To visualize the flow behavior within the rotating Couette flow environment, minute amounts of fluorescein dye were injected into the center of the flow container using a syringe pump. This dye was then redistributed within the flow by radial diffusion only when no disk rotation was used, and by radial diffusion and by circumferential advection when disk rotation was present. Associated effective diffusion coefficient values, for the latter arrangement, were compared to coefficients values with no disk rotation, which were due to molecular diffusion alone, in order to quantify enhancements due to elastic instabilities. Experiments were conducted using viscoelastic fluids, which were based on a 65% sucrose solution, with different polymer concentrations ranging from 0 ppm to 300 ppm. Associated Reynolds numbers based on the fluid depth and radially averaged maximum flow velocity ranged from 0.00 to 0.5. The resulting effective diffusion coefficient values for different flow shear rates and polymer concentrations quantified the onset of elastic instabilities, as well as significant and dramatic changes to local mass transport magnitudes, which are associated with the further development of elastic instabilities.

Simulating the Hydrodynamic Conditions of the Human Ascending Colon: A Digital Twin of the Dynamic Colon Model

The performance of solid oral dosage forms targeting the colon is typically evaluated using standardised pharmacopeial dissolution apparatuses. However, these fail to replicate colonic hydrodynamics. This study develops a digital twin of the Dynamic Colon Model; a physiologically representative in vitro model of the human proximal colon. Magnetic resonance imaging of the Dynamic Colon Model verified that the digital twin robustly replicated flow patterns under different physiological conditions (media viscosity, volume, and peristaltic wave speed). During local contractile activity, antegrade flows of 0.06–0.78 cm s−1 and backflows of −2.16–−0.21 cm s−1 were measured. Mean wall shear rates were strongly time and viscosity dependent although peaks were measured between 3.05–10.12 s−1 and 5.11–20.34 s−1 in the Dynamic Colon Model and its digital twin respectively, comparable to previous estimates of the USPII with paddle speeds of 25 and 50 rpm. It is recommended that viscosity and shear rates are considered when designing future dissolution test methodologies for colon-targeted formulations. In the USPII, paddle speeds >50 rpm may not recreate physiologically relevant shear rates. These findings demonstrate how the combination of biorelevant in vitro and in silico models can provide new insights for dissolution testing beyond established pharmacopeial methods.

Ultrasound 96 Probe Device Protocol for cancer cell treatment v1

Ultrasound is a sound wave with frequencies ranging between 20 kHz and 20 MHz. Ultrasound is able to temporarily and repeatedly open the BBB safely and enhance chemotherapeutic delivery without adverse effects.(Deprez et al., 2021). This novel technique in drug delivery benefits from the powerful ability of ultrasound to produce cavitation activity. Cavitation is the generation and activity of gas-filled bubbles in a medium exposed to ultrasound. As the pressure wave passes through the media, gas bubbles expand at low pressure and contract at high pressure. This leads to oscillation which produces a circulating fluid flow known as microstreaming around the bubble with velocities and shear rates proportional to the amplitude of the oscillation. At high amplitudes the associated shear forces can cut open liposomes (Wanigasekara et al., 2021; Deprez et al., 2021). Vesicles denser than the surrounding liquid are drawn into the shear field surrounding an oscillating bubble. If the shear stress is greater than the strength of the vesicle, it will burst and spill its contents. In a liposome, the vesicle will reform, often at a smaller size than before meeting the shear field. Hence, some interior liquid must be released during the break down. (Pitt et al., 2004) This protocol describes the use of an ultrasound probe to trigger the release of liposomes in glioblastoma cells. This method uses an ultrasound device which is set to the following parameters: Time = 3 min, Pulse = 59 /01, Amplitude = 20%. The ultrasound technique is an easy and reliable technique making it useful in the study of a variety of areas such as oncology. When applied to an ultrasonic transducer, the Pulser part of the instrument generates short, large amplitude electric pulses of controlled energy, which are transformed into short ultrasonic pulses. The VCX 750 is the ultrasonic liquid processor used for this experiment. It is powerful and versatile and can process a wide range of sample types and volumes for many different applications.

DERMATOLOGIC GELS SPREADABILITY MEASURING METHODS COMPARATIVE STUDY

Objective: The main objective of our study is the comprehensive analysis and characterization of the existing spreadability evaluation strategies, the comparison of the obtained results reproducibility and convergence through the example of the 9 most widely used dermatological gels. Methods: Dolobene®, Flucinar®, Ketorol®, Contractubex®, Dr. Theiss Venen gel®, Solcoseryl®, Deep Relief®, Hepatrombin® pharmacopoeia gel samples were analyzed using parallel-plate, “slip and drag”, and viscometry methods. Analysis was performed in flow mode at 32±0.2 °C, over shear rates ranging from 0 to 350 s−1, increasing over a period of 120 s, and was maintained at the superior limit for 10 s and then decreased during the same period. At least 5 replicates of each sample were evaluated, and the upward flow curves were fitted using the Casson mathematical model. Results: Solcoseryl® and Dolobene® showed the best spreadability in the parallel-plate method (3115.66±50.00 and 3316.63±50.00, respectively); Contractubex® and Dolobene showed the best spreadability in the “slip and drag” test (73.46±0.5 and 18.32±0.5, respectively); Solcoseryl® and Contractubex® showed the best spreadability in the viscometry test (43.86±0.5 and 76.92±0.5, respectively). Conclusion: This study analyzed the existing methods for determining the spreadability using commercially available samples of the dermatological gels as examples. The viscometric and the "Slip and drag" methods use different characteristics of spreadability, giving a complex evaluation of the measured parameter in vitro. Therefore, the combination of these two methods has the greatest prospects for reliable determination of this indicator.

A phenomenological theory-based viscosity model for shear thickening fluids

A viscosity model for shear thickening fluids (STFs) based on phenomenological theory is proposed. The model considers three characteristic regions of the typical material properties of STFs: a shear thinning region at low shear rates, followed by a sharp increase in viscosity above the critical shear rate, and subsequently a significant failure region at high shear rates. The typical S-shaped characteristic of the STF viscosity curve is represented using the logistic function, and suitable constraints are applied to satisfy the continuity of the viscosity model. Then, the Levenberg–Marquardt algorithm is introduced to fit the constitutive model parameters based on experimental data. Verification against experimental data shows that the model can predict the viscosity behavior of STF systems composed of different materials with different mass concentrations and temperatures. The proposed viscosity model provides a calculation basis for the engineering applications of STFs (e.g., in increasing impact resistance and reducing vibration).

SIPA in 10 milliseconds: VWF tentacles agglomerate and capture platelets under high shear

Shear-Induced Platelet Aggregation (SIPA) occurs under elevated shear rates (~10000 s-1) found in stenotic coronary and carotid arteries. The pathologically high-shear environment can lead to occlusive thrombosis by SIPA from the interaction of nonactivated platelets and von Willebrand factor (VWF) via glycoprotein Ib (GPIb)-A1 binding. This process under high shear rates is difficult to visualize experimentally with concurrent molecular- and cellular-resolutions. To understand this fast bonding, we employ a validated multiscale in-silico model incorporating measured molecular kinetics and a thrombosis-on-a-chip device to delineate the flow-mediated biophysics of VWF and platelets assembly into mural micro-thrombi. We show that SIPA begins with VWF elongation, followed by agglomeration of platelets in the flow by soluble VWF entanglement before mural capture of the agglomerate by immobilized VWF. The entire SIPA process occurs on the order of 10 ms with the agglomerate travelling a lag distance of a few hundred microns before capture, matching in vitro results. Increasing soluble VWF concentration by ~20x in silico leads to a 2~3x increase in SIPA rates, matching the increase in occlusion rates found in vitro. The morphology of mural aggregates is primarily controlled by VWF molecular weight (length), where normal-length VWF leads to cluster or elongated aggregates and ultra-long VWF leads to loose aggregates seen by others' experiments. Finally, we present phase diagrams of SIPA which provides biomechanistic rationales for a variety of thrombotic and hemostatic events in terms of platelet agglomeration and capture.

New Considerations on the Determination of the Apparent Shear Viscosity of Polymer Melt with Micro Capillary Dies

Capillary rheometers have been widely used for the rheological measurement of polymer melts. However, when micro capillary dies are used, the results are usually neither accurate nor consistent, even under the same measurement conditions. In this work, theoretical modeling and experimental studies were conducted for a more profound understanding of the mechanism by which the initial and boundary conditions influence the inaccuracy in the apparent shear viscosity determination with micro capillary dies (diameters: 500 μm, 200 μm, 100 μm). The results indicate that the amount of polymer initially in the barrel, the pre-compaction pressure and the capillary die diameter have a significant influence on the development of the micro scale inlet pressure, which directly determines the accuracy of the measurement at low and medium shear rates. The varying melt compressibility was confirmed to be the main factor directly related to the inaccuracy in the micro scale apparent shear viscosity determination. It is suggested that measures such as reducing the amount of polymer initially in the barrel and increasing the pre-compaction pressure could be used to reduce the measurement inaccuracy.

Rate Effects on Peak and Residual Strengths of Overconsolidated Clay in Ring Shear Tests

Overconsolidated (OC) clay soil is widely distributed in landslide slopes. This soil is often fissured, jointed, contains slickensides, and is prone to sliding. Thus, the shear strength behavior of OC clayey soil is complicated and has received much attention in the literature and in practice in terms of evaluating and predicting landslide stability. However, the behavior of the shear strength of OC clayey soil at different shear rates, as seen in ring shear tests, is still only understood to a limited extent and should be examined further, especially in terms of the residual strength characteristics. In this study, a number of ring shear tests were conducted on kaolin clay at overconsolidation ratios (OCRs) ranging from 1 to 6 under different shear displacement rates in the wide range of 0.02 mm/min to 20.0 mm/min to investigate the shear behavior and rate dependency of the shear strength of OC clay. Variations in the cohesion and friction angles of OC clay under different shear rates were also examined. The results indicated that the rate effects on the peak strength of OC and normally consolidated (NC) clays are opposite at fast shear displacement rates. At the residual state, as with NC clay, the positive rate effect on the residual strength is also exhibited in OC clay, but at a lower magnitude. Regarding the shear strength parameters, the variations in the cohesion and friction angles of OC clay at different shear rates were found to be different at peak and residual states.