Development of a bio-relevant dissolution test device simulating mechanical aspects present in the fed stomach

Area of Science:

• Pharmacokinetics and Drug Delivery
• Biomedical Engineering
• Gastrointestinal Physiology

Background:

• Standard in vitro dissolution testing often fails to replicate the complex mechanical and dynamic conditions within the human stomach after food intake.
• Understanding intragastric behavior is crucial for predicting in vivo drug release and absorption of oral dosage forms.
• Existing models lack the ability to precisely control and simulate the mechanical forces experienced by dosage forms in the fed state.

Purpose of the Study:

• To introduce and validate a novel Fed Stomach Model (FSM) designed to mimic intragastric conditions, focusing on mechanical aspects.
• To investigate the impact of simulated mechanical parameters (pressure, movement, flow rate) on the in vitro dissolution of diclofenac sodium bilayer extended-release tablets.
• To assess the FSM's capability to represent physiological variations in solid oral dosage form transit within the fed stomach.

Main Methods:

• Design and implementation of a computer-controlled, dynamic flow-through system (FSM) capable of simulating gastric vessel conditions.
• Utilizing magnetic marker monitoring to validate the simulation of intragastric movement velocities against in vivo data.
• Conducting dissolution experiments under varied conditions simulating fundus, antrum, and gastric emptying phases, while controlling pressure, dosage form movement, and pump rate.

Main Results:

• The FSM successfully simulated in vivo equivalent movement velocities of solid oral dosage forms.
• All simulated mechanical parameters (pressure, movement, pump rate) were found to be relevant to drug release.
• Dissolution rates varied significantly, with low release under fundic conditions (low shear stress) and higher release under antral and gastric emptying conditions (high stress).

Conclusions:

• The Fed Stomach Model (FSM) is a valuable tool for bio-relevant in vitro dissolution testing.
• The FSM enables precise and reproducible simulation of mechanical parameters characteristic of the fed stomach.
• This model provides crucial insights into how mechanical forces influence drug delivery from oral dosage forms in a physiologically relevant manner.