Computational model of drug dissolution in the stomach: effects of posture and gastroparesis on drug bioavailability

TL;DR

This study uses a biomimetic in-silico model to analyze how posture and gastroparesis affect drug dissolution and bioavailability in the stomach, revealing significant impacts on drug emptying rates.

Contribution

It introduces a realistic in-silico simulator to assess the effects of physiological and pathological conditions on drug dissolution and gastric emptying.

Findings

Posture changes can alter drug emptying by up to 83%.

Gastroparesis significantly reduces drug dissolution and emptying.

Neuropathic gastroparesis impacts gastric emptying more than myopathic gastroparesis.

Abstract

The oral route is the most common choice for drug administration because of convenience, low cost, and high patient compliance, but is also a complex route. The rate of dissolution and gastric emptying of the dissolved active pharmaceutical ingredient (API) into the duodenum is modulated by factors such as gastric motility, but current in-vitro procedures for assessing drug dissolution 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 this study we employ a biomimetic in-silico simulator based on the realistic anatomy and morphology of the stomach, to investigate the effect of body posture and stomach motility on drug bioavailability. The simulations show that changes in posture can 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 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.