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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. 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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3. 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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4. 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)

   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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5. Sucrose transport inside the phloem: Bridging hydrodynamics and geometric characteristics

   https://doi.org/10.1063/5.0151644  

   Nakad, Mazen ; Domec, Jean-Christophe ; Sevanto, Sanna ; Katul, Gabriel ( June 2023 , Physics of Fluids)

   In plants, the delivery of the products of photosynthesis is achieved through a hydraulic system labeled as phloem. This semi-permeable plant tissue consists of living cells that contract and expand in response to fluid pressure and flow velocity fluctuations. The Münch pressure flow theory, which is based on osmosis providing the necessary pressure gradient to drive the mass flow of carbohydrates, is currently the most accepted model for such sucrose transport. When this hypothesis is combined with the conservation of fluid mass and momentum as well as sucrose mass, many simplifications must be invoked to mathematically close the problem and to resolve the flow. This study revisits such osmotically driven flows by developing a new two-dimensional numerical model in cylindrical coordinates for an elastic membrane and a concentration-dependent viscosity. It is demonstrated that the interaction between the hydrodynamic and externally supplied geometrical characteristic of the phloem has a significant effect on the front speed of sucrose transport. These results offer a novel perspective about the evolutionary adaptation of plant hydraulic traits to optimize phloem soluble compounds transport efficiency. 

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