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.
more »
« less
Effect of stomach motility on food hydrolysis and gastric emptying: Insight from computational models
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.
more »
« less
- Award ID(s):
- 2019405
- PAR ID:
- 10417275
- Date Published:
- Journal Name:
- Physics of Fluids
- Volume:
- 34
- Issue:
- 11
- ISSN:
- 1070-6631
- Page Range / eLocation ID:
- 111909
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
A computational model of drug dissolution in the human stomach is developed to investigate the interaction between gastric flow and orally administrated drug in the form of a solid tablet. The stomach model is derived from the anatomical imaging data and the motion and dissolution of the drug in the stomach are modeled via fluid-structure interaction combined with mass transport simulations. The effects of gastric motility and the associated fluid dynamics on the dissolution characteristics are investigated. Two different pill densities are considered to study the effects of the gastric flow as well as the gravitational force on the motion of the pill. The average mass transfer coefficient and the spatial distributions of the dissolved drug concentration are analyzed in detail. The results show that the retropulsive jet and recirculating flow in the antrum generated by the antral contraction wave play an important role in the motion of the pill as well as the transport and mixing of the dissolved drug concentration. It is also found that the gastric flow can increase the dissolution mass flux, especially when there is substantial relative motion between the gastric flow and the pill.more » « less
-
more » « less
Pyloric interventions are surgical procedures employed to increase the gastric emptying rate in gastroparesis patients. In this study, we use an
in silico model to investigate the consequences of pyloric intervention on gastric flow and emptying for two phenotypes of gastroparesis: antral hypomotility and decreased gastric tone. The transpyloric pressure gradient predicted by thein silico model, based on viscous fluid flow equations, is compared againstin vivo measurements. Both phenotypes exhibit a similar pre-procedural emptying rate reduction, but after pyloric surgery, antral hypomotility case with preserved gastric tone shows significant improvements in emptying rates, up to 131%, accompanied by bile reflux from the duodenum into the stomach. Conversely, severely reduced gastric tone cases exhibited a post-procedural reduction in the net emptying rate due to the relatively larger bile reflux. In cases with a combination of antral hypomotility and reduced gastric tone, post-procedural improvements were observed only when both conditions were mild. Our findings highlight the pivotal role of the relative increase in pyloric orifice diameter in determining post-operative emptying rates. The study suggests a possible explanation for the selective response of patients toward these procedures and underscores the potential ofin silico modelling to generate valuable insights to inform gastric surgery. -
more » « less
Abstract Climate change is leading to an increase in severity, frequency, and distribution of harmful algal blooms across the globe. For many harmful algae species in eutrophic lakes, the formation of such blooms is controlled by three factors: the lake hydrodynamics, the vertical motility of the algae organisms, and the ability of the organisms to form colonies. Here, using the common cyanobacterium
Microcystis aeruginosa as an example, we develop a model that accounts for both vertical transport and colony dynamics. At the core of this treatment is a model for aggregation. For this, we used Smoluchowski dynamics containing parameters related to Brownian motion, turbulent shear, differential setting, and cell‐to‐cell adhesion. To arrive at a complete description of bloom formation, we place the Smoluchowski treatment as a reaction term in a set of one‐dimensional advection‐diffusion equations, which account for the vertical motion of the algal cells through molecular and turbulent diffusion and self‐regulating buoyant motion. Results indicate that Smoluchowski aggregation qualitatively describes the colony dynamics ofM. aeruginosa . Further, the model demonstrates wind‐induced mixing is the dominant aggregation process, and the rate of aggregation is inversely proportional to algal concentration. Because blooms ofMicrocystis typically consist of large colonies, both of these findings have direct consequences to harmful algal bloom formation. While the theoretical framework outlined in this manuscript was derived forM. aeruginosa , both motility and colony formation are common among bloom‐forming algae. As such, this coupling of vertical transport and colony dynamics is a useful step for improving forecasts of surface harmful algal blooms. -
This paper addresses peristaltic flow induced in a non-axisymmetric annular tube by a periodic small-amplitude wave of arbitrary shape propagating axially along its inner surface, assumed to be a circular cylinder. The study is motivated by recent in vivo experimental observations pertaining to the flow of cerebrospinal fluid along the perivascular spaces of cerebral arteries. The analysis employs the lubrication approximation, describing low-Reynolds-number peristaltic flow in the long-wavelength approximation. Closed-form analytic expressions are derived for the average pumping rate in infinitely long tubes and also in tubes of finite length. Consideration is also given to the transverse motion arising in non-axisymmetric tubes. For small-amplitude waves, the solution is reduced to the integration of a parameter-free Stokes-flow problem, which is solved for relevant cross-sectional shapes, with closed-form analytical results derived for thin canals.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1063/5.0120933
