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1. Computational modeling of drug dissolution in the human stomach: Effects of posture and gastroparesis on drug bioavailability

   https://doi.org/10.1063/5.0096877  

   Lee, J. H.; Kuhar, S.; Seo, J.-H.; Pasricha, P. J.; Mittal, R. (August 2022, Physics of Fluids)

   The oral route is the most common choice for drug administration because of several advantages, such as convenience, low cost, and high patient compliance, and the demand and investment in research and development for oral drugs continue to grow. The rate of dissolution and gastric emptying of the dissolved active pharmaceutical ingredient (API) into the duodenum is modulated by gastric motility, physical properties of the pill, and the contents of the stomach, but current in vitro procedures for assessing dissolution of oral drugs are limited in their ability to recapitulate this process. This is particularly relevant for disease conditions, such as gastroparesis, that alter the anatomy and/or physiology of the stomach. In silico models of gastric biomechanics offer the potential for overcoming these limitations of existing methods. In the current study, we employ a biomimetic in silico simulator based on the realistic anatomy and morphology of the stomach (referred to as “StomachSim”) to investigate and quantify the effect of body posture and stomach motility on drug bioavailability. The simulations show that changes in posture can potentially have a significant (up to 83%) effect on the emptying rate of the API into the duodenum. Similarly, a reduction in antral contractility associated with gastroparesis can also be found to significantly reduce the dissolution of the pill as well as emptying of the API into the duodenum. The simulations show that for an equivalent motility index, the reduction in gastric emptying due to neuropathic gastroparesis is larger by a factor of about five compared to myopathic gastroparesis. 

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2. Effects of Pore‐Scale Three‐Dimensional Flow and Fluid Inertia on Mineral Dissolution

   https://doi.org/10.1029/2024WR038176  

   Lee, Woonghee; Chen, Michael_A; Bresciani, Etienne; Toner, Brandy_M; Kang, Peter_K (April 2025, Water Resources Research)

   Abstract Mineral dissolution releases ions into fluids and alters pore structures, affecting geochemistry and subsurface fluid flow. Thus, mineral dissolution plays a crucial role in many subsurface processes and applications. Pore‐scale fluid flow often controls mineral dissolution by controlling concentration gradients at fluid‐solid interfaces. In particular, recent studies have shown that fluid inertia can significantly affect reactive transport in porous and fractured media by inducing unique flow structures such as recirculating flows. However, the effects of pore‐scale flow and fluid inertia on mineral dissolution remain largely unknown. To address this knowledge gap, we combined visual laboratory experiments and micro‐continuum pore‐scale reactive transport modeling to investigate the effects of pore‐scale flow and fluid inertia on mineral dissolution dynamics. Through flow topology analysis, we identified unique patterns of 2D and 3D recirculating flows and their distinctive effects on dissolution. The simulation results revealed that 3D flow topology and fluid inertia dramatically alter the spatiotemporal dynamics of mineral dissolution. Furthermore, we found that the 3D flow topology fundamentally changes the upscaled relationship between porosity and reactive surface area compared to a conventional relationship, which is commonly used in continuum‐scale modeling. These findings highlight the critical role of 3D flow and fluid inertia in modeling mineral dissolution across scales, from the pore scale to the Darcy scale. 

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3. Measuring dissolution profiles of single controlled-release drug pellets

   https://doi.org/10.1038/s41598-020-76089-z  

   Bhakta, Heran C.; Lin, Jessica M.; Grover, William H. (November 2020, Scientific Reports)

   Abstract Many solid-dose oral drug products are engineered to release their active ingredients into the body at a certain rate. Techniques for measuring the dissolution or degradation of a drug product in vitro play a crucial role in predicting how a drug product will perform in vivo. However, existing techniques are often labor-intensive, time-consuming, irreproducible, require specialized analytical equipment, and provide only “snapshots” of drug dissolution every few minutes. These limitations make it difficult for pharmaceutical companies to obtain full dissolution profiles for drug products in a variety of different conditions, as recommended by the US Food and Drug Administration. Additionally, for drug dosage forms containing multiple controlled-release pellets, particles, beads, granules, etc. in a single capsule or tablet, measurements of the dissolution of the entire multi-particle capsule or tablet are incapable of detecting pellet-to-pellet variations in controlled release behavior. In this work, we demonstrate a simple and fully-automated technique for obtaining dissolution profiles from single controlled-release pellets. We accomplished this by inverting the drug dissolution problem: instead of measuring the increase in the concentration of drug compounds in the solution during dissolution (as is commonly done), we monitor the decrease in the buoyant mass of the solid controlled-release pellet as it dissolves. We weigh single controlled-release pellets in fluid using a vibrating tube sensor, a piece of glass tubing bent into a tuning-fork shape and filled with any desired fluid. An electronic circuit keeps the glass tube vibrating at its resonance frequency, which is inversely proportional to the mass of the tube and its contents. When a pellet flows through the tube, the resonance frequency briefly changes by an amount that is inversely proportional to the buoyant mass of the pellet. By passing the pellet back-and-forth through the vibrating tube sensor, we can monitor its mass as it degrades or dissolves, with high temporal resolution (measurements every few seconds) and mass resolution (700 nanogram resolution). As a proof-of-concept, we used this technique to measure the single-pellet dissolution profiles of several commercial controlled-release proton pump inhibitors in simulated stomach and intestinal contents, as well as comparing name-brand and generic formulations of the same drug. In each case, vibrating tube sensor data revealed significantly different dissolution profiles for the different drugs, and in some cases our method also revealed differences between different pellets from the same drug product. By measuring any controlled-release pellets, particles, beads, or granules in any physiologically-relevant environment in a fully-automated fashion, this method can augment and potentially replace current dissolution tests and support product development and quality assurance in the pharmaceutical industry. 

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4. Heat and mass transport from neutrally suspended oblate spheroid in simple shear flow

   https://doi.org/10.1063/5.0140778  

   Wang, Yanxing; Wan, Hui; Gonzalez Pizarro, Ruben; Lim, Seokbin; Shu, Fangjun (March 2023, Physics of Fluids)

   Through high-fidelity numerical simulation based on the lattice Boltzmann method, we have conducted an in-depth study on the heat and mass transport from an oblate spheroid neutrally suspended in a simple shear flow. In the simulation, the temperature and mass concentration are modeled as a passive scalar released at the surface of the spheroid. The fluid dynamics induced by the interaction between the carrier fluid and the suspended spheroid, as well as the resultant scalar transport process, have been extensively investigated. A coupled transport mechanism comprising several components of the flow around the oblate spheroid has been identified. The effects of the Reynolds number and the aspect ratio of the spheroid on the flow characteristics and scalar transport rate are examined. The variation of the nondimensional scalar transport rate suggests that the effect of spheroid shape on scalar transfer rate can be decoupled from the effects of Peclet and Reynolds numbers, which facilitates the development of a correlation of scalar transfer rate for oblate spheroids based on the well-developed correlations for a sphere. 

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5. Effect of stomach motility on food hydrolysis and gastric emptying: Insight from computational models

   https://doi.org/10.1063/5.0120933  

   Kuhar, Sharun; Lee, Jae Ho; Seo, Jung-Hee; Pasricha, Pankaj J; Mittal, Rajat (November 2022, Physics of Fluids)

   The peristaltic motion of stomach walls combines with the secretion of digestive enzymes to initiate the process that breaks down food. In this study, the mixing, breakdown, and emptying of a liquid meal containing protein is simulated in a model of a human stomach. In this model, pepsin, the gastric enzyme responsible for protein hydrolysis, is secreted from the proximal region of the stomach walls and allowed to react with the contents of the stomach. The velocities of the retropulsive jet induced by the peristaltic motion, the emptying rate, and the extent of hydrolysis are quantified for a control case as well as for three other cases with reduced motility of the stomach, which may result from conditions such as diabetes mellitus. This study quantifies the effect of stomach motility on the rate of food breakdown and its emptying into the duodenum and we correlate these observations with the mixing in the stomach induced by the wall motion. 

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