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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. 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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3. Effects of rhamnolipid biosurfactant on the dissolution and transport of silver nanoparticles in porous media

   https://doi.org/10.1039/D1EN00185J  

   Liao, Shuchi ; Liu, Chen ; Pinchbeck, Dorothea ; Cápiro, Natalie L. ; Fortner, John D. ; Abriola, Linda M. ; Pennell, Kurt D. ( September 2021 , Environmental Science: Nano)

   The effects of nanoscale silver (nAg) particles on subsurface microbial communities can be influenced by the presence of biosurfactants, which have been shown to alter nanoparticle surface properties. Batch and column studies were conducted to investigate the influence of rhamnolipid biosurfactant (1–50 mg L −1 ) on the stability and mobility of silver nanoparticles (16 ± 4 nm) in batch reactors and water-saturated columns with three solution chemistries: pH = 4 and dissolved oxygen concentration (DO) = 8.8 mg L −1 , pH = 7 and DO = 8.8 mg L −1 , pH = 7 and DO = 2.0 mg L −1 . In batch studies, the presence of rhamnolipid (2–50 mg L −1 ) reduced nAg dissolution by 83.3–99.1% under all pH and DO conditions. Improved nAg stability was observed when rhamnolipid was present in batch reactors at pH = 7 ± 0.2, where the hydrodynamic diameter remained constant (∼50 nm) relative to rhamnolipid-free controls (increased to >230 nm) in 48 hours. Column experiments conducted at pH 4.0 ± 0.2 demonstrated that co-injection of nAg with rhamnolipid (2, 5 and 50 mg L −1 ) decreased Ag + breakthrough from ∼22% of total applied mass in rhamnolipid-free columns to less than 8.1% in the presence of rhamnolipid and altered the shape of the nAg retention profile from a hyper-exponential to a uniform distribution. Column experiments performed at pH 7.0 ± 0.2 and DO levels of either ∼2.0 or ∼8.8 mg L −1 showed that co-injection of 5 mg L −1 and 50 mg L −1 rhamnolipid increased nAg mass breakthrough by 25–40% and ∼80%, respectively, enhancements in nAg stability and mobility were attributed to rhamnolipid adsorption on nAg surfaces, which effectively slowed the oxidation and thus release of Ag + , and adsorption of rhamnolipid on the porous medium, which competed for nAg attachment sites. These results indicate that the presence of rhamnolipid significantly influenced nAg dissolution and mobility under dynamic flow conditions. A mathematical model based on modified filtration theory (MFT) accurately reproduced nAg transport and retention behavior when aggregation and reaction processes were minimal and when rhamnolipid was present, providing a tool to predict the effects of biosurfactants on nAg transport in porous media. 

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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. Advection-enhanced heat and mass transport from neutrally suspended droplet in simple shear flow

   https://doi.org/10.1063/5.0153117  

   Wang, Yanxing ; Vazquez Alvarez, David ; Wan, Hui ; Gonzalez Pizarro, Ruben ; Shu, Fangjun ( June 2023 , Physics of Fluids)

   Advection-enhanced heat and mass transport from a single droplet neutrally suspended in a simple shear flow has been studied using high-fidelity numerical simulation. The capillary number ranges from 0.01 to 0.5, which encompasses the entire range of small deformation, large deformation, and breakup of the droplets. The Reynolds number is from 0.01 to 1, including regions of both weak and strong advection. The temperature and mass concentration are modeled as the concentration of a passive scalar released at the droplet surface. Two Schmidt numbers, 10 and 100, are considered, for which flow advection plays a role in the transport of passive scalar. For unbroken droplets, the interaction between the carrier fluid and the suspended droplet leads to several different flows around the droplet. The fluid motions together with scalar diffusion constitute a coupled transport mechanism for passive scalar. The dependence of scalar release rate on Reynolds and Peclet numbers can be roughly described by the correlation for a rigid sphere. For broken droplets, the basic flow features around the droplet during the process of elongation and breakup are similar to those of an unbroken droplet. The variation of the scalar release rate can be decomposed into several stages, corresponding to the process of droplet elongation and breakup. The variation of the scalar release rate exhibits a high correlation with the capillary, Reynolds, and Peclet numbers. This suggests that it is feasible to develop an empirical model that incorporates the effects of the number and size distributions of child droplets after breakup.

    

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