Effect of Posture and Motility on Drug Availability in the Human Stomach

“The good thing about science is that it’s true whether or not you believe in it.” Neil deGrasse Tyson

“Imagination is more important than knowledge.” Albert Einstein

Introduction:  Taking something by mouth is a common and relatively easy way to administer a drug. By contrast, when you carefully consider the route, it is a more complex scenario than imagined. Think about the path from the mouth to the gastrointestinal tract where the drug is absorbed. Alternatively, think about taking your carbidopa/levodopa pill by swallowing it versus placing it under your tongue. Which method is faster? Hopefully, you assume taking the medication by placing it under your tongue and bypassing the gut is the quicker method/route. But the usual way to take a pill is by swallowing it, which is the topic of this post.

Where is this story going? A research team at Johns Hopkins found out that posture and gastroparesis drastically changed the bioavailability of drugs. That is, standing up or laying on your right, left, or back. This computer modeling paper examined the dissolution of a drug in the stomach based on posture and gastroparesis. Gastroparesis is a term that means partial paralysis of the stomach. As a result, the stomach cannot effectively empty itself, which slows the movement (motility) of contents through your digestive system.

The paper was published in the Journal named “Physics of Fluids,” and the complete citation is as follows: Lee, Jae Ho, Sharun Kuhar, J-H. Seo, Pankaj J. Pasricha, and Rajat Mittal. “Computational modeling of drug dissolution in the human stomach: Effects of posture and gastroparesis on drug bioavailability.” Physics of Fluids 34, no. 8 (2022): 081904.

“Science cannot solve the ultimate mystery of nature. And that is because, in the last analysis, we ourselves are a part of the mystery that we are trying to solve.” Max Planck

Digesting a Pill: This paper aimed to devise a process to measure how a human stomach and gastrointestinal tract can dissolve a pill once swallowed. This research group is composed of computer scientists, and they did what was termed an in silico study [that is, (of scientific experiments or research) conducted or produced using computer modeling or computer simulation.].

And the question they studied was to devise a computer model that measured the dissolution rate and gastric emptying of the dissolved active pharmaceutical ingredient (API) into the duodenum. They assumed that this rate of pill dissolution was altered or modulated by (a) gastric motility, (b) physical properties of the pill, and (c) the contents of the stomach. And they stated that currently used procedures for determining these processes are limited in their ability to recapitulate this process.

“If we would serve science, we must extend her limits, not only as far as our own knowledge is concerned, but in the estimation of others.” Rudolf Virchow

Existing Methods or Models to Measure Drug Dissolution: The two most widely used and accepted methods to measure drug dissolution are shown in the following slide (adapted from the paper). These techniques do work. Still, they have some deficiencies, and the authors sought to develop a newer model system to take these deficiencies into account.

They wanted to have a model system that could mimic disease conditions that alter the anatomy or physiology of the stomach. And this is relevant to Parkinson’s. For example, the condition of gastroparesis, simply a change in gastric motility, can be promoted by several diseases/conditions such as Parkinson’s, diabetes, and gastric bypass surgery. Thus, it would make sense that if someone is creating a new drug for Parkinson’s, this new model system might be useful in evaluating the drug parameters of such a compound in a setting of Parkinson’s. Their study aimed to model the effect of posture and gastroparesis on drug dissolution in the stomach and the release of drug into the duodenum.

“No amount of experimentation can ever prove me right; a single experiment can prove me wrong.” Albert Einstein

Computer Model of Pill Dissolution: Computational fluid dynamics (CFD) has been used to assess medical devices. The model relies on an in silico simulation to gather the data under varying physiological/pathological conditions the pill may encoder in the stomach. The authors used a computational modeling platform to simulate drug dissolution in an image-based human stomach model. Other groups have done such modeling before. The authors have extended their model system by including the pyloric opening and using CFD that enable them to measure how much of the dissolved API (active pharmaceutical ingredient) is mixed and transported in the stomach and released into the duodenum.

The schematic below demonstrates the 3-dimensional idea behind posture being measured (left panel), the computer model tries to emulate the human digestive tract (middle panel), and the influence of gastroparesis to alter pill dissolution. (right panel).

The model system created here is based on the human anatomy of the stomach as described in the scheme below (adapting the author’s figure from the paper).

Influence on Posture in Pill Dissolution: The hypothesis being tested was since the pill is denser than the dissolution medium, the effect of the direction will significantly affect the pill motion and, thereby, the rate of dissolution and release of the drug from the pill. I thought this initially, but it is not due to gravitational force (g). The schematic shows the idea behind the testing of posture.

They found that gravity does not affect the emptying of the stomach’s liquid content, but the volume matters. They explain that with constant density in all cases, the primary determinant of fluid emptying rate is the antral contraction, which is the same for all cases [The terminal antral contraction describes a well-controlled compaction of the terminal region of the antrum.]. Their results show that leaning right (posture 1, leaning right by 45°) yields a significant increase in the dissolved mass released into the duodenum compared to other positions. Conversely, leaning left (posture 2, leaning left by 45°) leads to a substantial decrease.

Thus, taking pills while lying on the right side was the best. This position was best at sending drugs through the stomach to obtain a dissolution rate 2.3 times quicker than taking a pill in an upright posture. By contrast, lying on the left side was the worst. Standing upright was an excellent second choice, essentially tied in effectiveness with leaning back (leaning back by 45°). So if bedridden, how you swallow pills based on your posture would matter to reach effective drug dissolution through the stomach.

“All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.” Arthur Schopenhauer

Effect of Gastroparesis on Pill Dissolution: Gastroparesis is caused by a decrease in the number of contractions, the amplitude of contractions, or both. Gastroparesis is usually further delineated as caused by neuropathy (damaged vagus nerve), myopathy (increased fibrosis or degeneration of smooth muscle cells), or alterations in both. Altering the mode of contractions as defined here led to a considerable reduction in time for pill dissolution. Thus, if gastroparesis is part of your Parkinson’s, it could slow down drug delivery from reaching the intestinal tract where the drug is likely absorbed.

“You can have data without information, but you cannot have information without data.” Daniel Keys Moran

Conclusions: This paper shows that the content of your stomach, motility, position, and fluid properties all modify the availability of a drug in a pill. And these changes are further limited by contractions of the stomach. Together these ‘conditions’ pose a complicated scenario for a medicine containing a vital drug for you to take. One must also realize this is a computer model of a very complex physiological situation. I am neither a computer scientist nor a mathematician, so I must assume their model was valid. I struggled to understand the model’s math but followed the physiology. Reading the interpretations of their work and what it means to us as we routinely swallow pills was fascinating.

“But in physics I soon learned to scent out the paths that led to the depths, and to disregard everything else, all the many things that clutter up the mind, and divert it from the essential. The hitch in this was, of course, the fact that one had to cram all this stuff into one’s mind for the examination, whether one liked it or not.” Albert Einstein

Cover photo image by Andris Dumins from Pixabay