Capillary Corner Flows With Partial and Nonwetting Fluids

Capillary flow in containers or conduits with interior corners are common place in nature and industry. The majority of investigations addressing such flows solve the problem numerically in terms of a friction factor for flows along corners with contact angles below the Concus-Finn critical wetting condition for the particular conduit geometry of interest. This research effort provides missing numerical data for the flow resistance function F(sub i) for partially and nonwetting systems above the Concus-Finn condition. In such cases the fluid spontaneously de-wets the interior corner and often retracts into corner-bound drops. A banded numerical coefficient is desirable for further analysis and is achieved by careful selection of length scales x(sub s) and y(sub s) to nondimensionalize the problem. The optimal scaling is found to be identical to the wetting scaling, namely x(sub s) = H and y(sub s) = Htan (alpha), where H is the height from the corner to the free surface and a is the corner half-angle. Employing this scaling produces a relatively weakly varying flow resistance F(sub i) and for subsequent analyses is treated as a constant. Example solutions to steady and transient flow problems are provided that illustrate applications of this result

Accelerated spreading of inviscid droplets prompted by the yielding of strongly elastic interfacial films

The complexity associated with droplets spreading on surfaces has attracted significant interest for several decades. Sustained activity results from the many natural and manufactured systems that are reliant on droplet-substrate interactions and spreading. Interfacial shear rheology and its influence on the dynamics of droplet spreading has to date received little attention. In the current study, saponin β-aescin was used as an interfacial shear rheology modifier, partitioning at the air-water interface to form a strongly elastic interface (G’/G” ∼ 6) within 1 min aging. The droplet spreading dynamics of Newtonian (water, 5 wt% ethanol, 0.0015 wt% N-dodecyl β-D-glucopyranoside) and non-Newtonian (xanthan gum) fluids were shown to proceed with a time-dependent power-law dependence of ∼0.50 and ∼0.10 (Tanner’s law) in the inertial and viscous regimes of spreading, respectively. However, water droplets stabilized by saponin β-aescin were shown to accelerate droplet spreading in the inertial regime with a depreciating time-dependent power-law of 1.05 and 0.61, eventually exhibiting a power-law dependence of ∼ 0.10 in the viscous regime of spreading. The accelerated rate of spreading is attributed to the potential energy as the interfacial film yields as well as relaxation of the crumpled interfacial film during spreading. Even though the strongly elastic film ruptures to promote droplet spreading, interfacial elasticity is retained enhancing the dampening of droplet oscillations following detachment from the dispensing capillary

A Better Nondimensionalization Scheme for Slender Laminar Flows: The Laplacian Operator Scaling Method

A scaling of the two-dimensional Laplacian operator is demonstrated for certain solutions (at least) to Poisson’s equation. It succeeds by treating the operator as a single geometric scale entity. The belated and rather subtle method provides an efficient assessment of the geometrical dependence of the problem and is preferred when practicable to the hydraulic diameter or term-by-term scaling for slender fully developed laminar flows. The improved accuracy further reduces the reliance of problems on widely varying numerical data or cumbersome theoretical forms and improves the prospects of exact or approximate theoretical analysis. Simple example problems are briefly described that demonstrate the application and potential of the method

PBPK modeling to predict drug‐drug interactions of ivosidenib as a perpetrator in cancer patients and qualification of the Simcyp platform for CYP3A4 induction

Abstract Ivosidenib is a potent, targeted, orally active, small‐molecule inhibitor of mutant isocitrate dehydrogenase 1 (IDH1) that has been approved in the United States for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) who are greater than or equal to 75 years of age or ineligible for intensive chemotherapy, and those with relapsed or refractory AML, with a susceptible IDH1 mutation. Ivosidenib is an inducer of the CYP2B6, CYP2C8, CYP2C9, and CYP3A4 and an inhibitor of P‐glycoprotein (P‐gp), organic anion transporting polypeptide‐1B1/1B3 (OATP1B1/1B3), and organic anion transporter‐3 (OAT3) in vitro. A physiologically‐based pharmacokinetic (PK) model was developed to predict drug‐drug interactions (DDIs) of ivosidenib in patients with AML. The in vivo CYP3A4 induction effect of ivosidenib was quantified using 4β‐hydroxycholesterol and was subsequently verified with the PK data from an ivosidenib and venetoclax combination study. The verified model was prospectively applied to assess the effect of multiple doses of ivosidenib on a sensitive CYP3A4 substrate, midazolam. The simulated midazolam geometric mean area under the curve (AUC) and maximum plasma concentration (Cmax) ratios were 0.18 and 0.27, respectively, suggesting ivosidenib is a strong inducer. The model was also used to predict the DDIs of ivosidenib with CYP2B6, CYP2C8, CYP2C9, P‐gp, OATP1B1/1B3, and OAT3 substrates. The AUC ratios following multiple doses of ivosidenib and a single dose of CYP2B6 (bupropion), CYP2C8 (repaglinide), CYP2C9 (warfarin), P‐gp (digoxin), OATP1B1/1B3 (rosuvastatin), and OAT3 (methotrexate) substrates were 0.90, 0.52, 0.84, 1.01, 1.02, and 1.27, respectively. Finally, in accordance with regulatory guidelines, the Simcyp modeling platform was qualified to predict CYP3A4 induction using known inducers and sensitive substrates

Modelling of droplet absorption and evaporation during pharmaceutical tablet coating

The shelf life of a pharmaceutical tablet is affected by the amount of water that interacts with it during the aqueous film coating process. The purpose of this work is to simulate the spreading, absorption and evaporation of water droplets after impact on a porous tablet core. We divided the spreading, absorption and evaporation phenomena into three separate phases: the kinematic, the capillary and the evaporation phases. For the kinematic phase, we modified 1-D spreading models found in the literature which solve the kinetic energy balance equation. Subsequently, for the capillary phase we solved the Navier-Stokes equation using the lubrication approximation theory. For the evaporation phase, we developed a novel model that treats the tablet as a particle with a wet core surrounded by a dry crust. Our numerical results were in good agreement with recent experimental data found in the literature