More Than a Gut FeelingâA Combination of Physiologically Driven Dissolution and Pharmacokinetic Modeling as a Tool for Understanding Human Gastric Motility.
Mol Pharm
; 21(8): 3824-3837, 2024 Aug 05.
Article
in En
| MEDLINE
| ID: mdl-38958668
ABSTRACT
In vivo studies of formulation performance with in vitro and/or in silico simulations are often limited by significant gaps in our knowledge of the interaction between administered dosage forms and the human gastrointestinal tract. This work presents a novel approach for the investigation of gastric motility influence on dosage form performance, by combining biopredictive dissolution tests in an innovative PhysioCell apparatus with mechanistic physiology-based pharmacokinetic modeling. The methodology was based on the pharmacokinetic data from a large (n = 118) cohort of healthy volunteers who ingested a capsule containing a highly soluble and rapidly absorbed drug under fasted conditions. The developed dissolution tests included biorelevant media, varied fluid flows, and mechanical stress events of physiological timing and intensity. The dissolution results were used as inputs for pharmacokinetic modeling that led to the deduction of five patterns of gastric motility and their prevalence in the studied population. As these patterns significantly influenced the observed pharmacokinetic profiles, the proposed methodology is potentially useful to other in vitro-in vivo predictions involving immediate-release oral dosage forms.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Solubility
/
Gastrointestinal Motility
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Mol Pharm
Journal subject:
BIOLOGIA MOLECULAR
/
FARMACIA
/
FARMACOLOGIA
Year:
2024
Document type:
Article
Affiliation country: