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

Abstract

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, 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, reduction in gastric emptying due to neuropathic gastroparesis is larger by a factor of about five compared to myopathic gastroparesis.

Effect of Antral Motility on Food Hydrolysis and Gastric Emptying from the Stomach: Insights from Computational Models

“…However, for all cases, initially there is an exponential rise which changes into a linear growth that eventually asymptotes to a value as t → ∞. The figure also shows trend lines obtained by fitting the modified Elashoff's model, which has also been used by others to capture emptying of different gastric components 8,[43][44][45] . It is a sigmoid shape function given by:…”

“…A stabilized bi-conjugate gradient method is used to solve the pressure Poisson equation. More details on the numerical methodology and grid convergence study can be found in earlier works 8,33 .…”

“…For researchers in the field of medicine, stomach motility plays a key role in gastric disorders such as gastroesophageal reflux disease (GERD), gastroparesis (delayed emptying), dumping syndrome (rapid emptying), as well as in the pathophysiology of diabetes and functional dyspepsia [4][5][6][7] , because the rate at which the stomach empties its contents affects the rate at which the nutrients get absorbed in the intestines. Gastric emptying is also important for drug delivery via oral administration as it determines the time it takes for effects of the drug to manifest themselves 8 . For researchers in the arena of nutrition and food design, a better understanding of the biomechanical processes involved in gastric digestion could help answer questions related to bioavailability of nutrients and the variation in emptying rates and food hydrolysis with food properties.…”

“…How does this mixing, hydrolysis and emptying change with variations in gastric motility? In the past, our model has been used to study oral pill dissolution and API delivery into the intestines 8,33 . Here, we use it to model the hydrolysis of a liquid meal containing protein.…”

Comparing Salivary Caffeine Kinetics of 13C and 12C Caffeine for Gastric Emptying of 50 mL Water

“…As is common in MRI studies, the subjects were in the supine position during our experiment. Recent work highlighted the effect of body position on gastric emptying, and the effect of different volumes on gastric emptying might be different in the upright position [ 29 , 30 ]. Nonetheless, the two previously mentioned studies by Oberle et al and Wong et al were carried out mainly in the upright position, and comparable findings on the gastric emptying rates of different volumes were observed.…”