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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Computational modeling of drug dissolution in the human stomach: Effects of posture and gastroparesis on drug bioavailability
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August 2022
Research Article|
August 09 2022
Computational modeling of drug dissolution in the human stomach: Effects of posture and gastroparesis on drug bioavailability
J. H. Lee (이재호)
;
J. H. Lee (이재호)
a)
(Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Visualization, Writing – original draft, Writing – review & editing)
1
Department of Mechanical Engineering, Johns Hopkins University
, Baltimore, Maryland 21218, USA
2
Institute for Computational Medicine, Johns Hopkins University
, Baltimore, Maryland 21218, USA
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S. Kuhar
;
S. Kuhar
(Conceptualization, Formal analysis, Investigation, Visualization, Writing – original draft, Writing – review & editing)
1
Department of Mechanical Engineering, Johns Hopkins University
, Baltimore, Maryland 21218, USA
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J.-H. Seo (서정희)
;
J.-H. Seo (서정희)
(Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Software, Supervision, Validation, Writing – original draft, Writing – review & editing)
1
Department of Mechanical Engineering, Johns Hopkins University
, Baltimore, Maryland 21218, USA
2
Institute for Computational Medicine, Johns Hopkins University
, Baltimore, Maryland 21218, USA
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P. J. Pasricha;
P. J. Pasricha
(Conceptualization, Funding acquisition, Writing – original draft, Writing – review & editing)
3
Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine
, Baltimore, Maryland 21205, USA
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R. Mittal
R. Mittal
b)
(Conceptualization, Formal analysis, Funding acquisition, Methodology, Project administration, Resources, Software, Supervision, Writing – original draft, Writing – review & editing)
1
Department of Mechanical Engineering, Johns Hopkins University
, Baltimore, Maryland 21218, USA
2
Institute for Computational Medicine, Johns Hopkins University
, Baltimore, Maryland 21218, USA
4
Department of Medicine, Johns Hopkins School of Medicine
, Baltimore, Maryland 21205, USA
b)Author to whom correspondence should be addressed: [email protected]
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a)
Present address: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20903, USA.
b)Author to whom correspondence should be addressed: [email protected]
Physics of Fluids 34, 081904 (2022)
Article history
Received:
April 22 2022
Accepted:
June 23 2022
Citation
J. H. Lee, S. Kuhar, J.-H. Seo, P. J. Pasricha, R. Mittal; Computational modeling of drug dissolution in the human stomach: Effects of posture and gastroparesis on drug bioavailability. Physics of Fluids 1 August 2022; 34 (8): 081904. https://doi.org/10.1063/5.0096877
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