Size discrimination in rat and mouse gastric emptying

Area of Science:

• Pharmacokinetics and Drug Delivery
• Gastrointestinal Physiology
• Biomedical Engineering

Background:

• Understanding gastric emptying is crucial for oral drug formulation and delivery.
• Particle size is a key factor influencing gastrointestinal transit and drug absorption.
• Polymethyl methacrylate (PMMA) microcapsules and beads are used as model particles for studying gastric emptying.

Purpose of the Study:

• To investigate the relationship between particle size and gastric emptying in rodents.
• To determine the cut-off particle size for gastric emptying in ICR mice and Sprague Dawley (SD) rats.
• To inform the design of oral dosage forms and optimize drug delivery systems.

Main Methods:

• Radiolabeled insoluble PMMA microcapsules/beads (50 µm–3 mm) were prepared with (99m)Tc-DTPA.
• These particles were administered to ICR mice and SD rats via oral gavage.
• Gastric emptying was monitored using gamma scintigraphy for up to 4 hours post-administration.

Main Results:

• Smaller PMMA particles (50-100 µm) and beads (0.5-1 mm) showed slower gastric emptying in both species.
• In ICR mice, gastric emptying did not significantly differ for microcapsules between 100-300 µm.
• In SD rats, beads >2 mm exhibited significantly retarded gastric emptying, with some lodging in the esophagus.

Conclusions:

• The cut-off particle size for gastric emptying could not be determined in ICR mice due to dosing limitations.
• In SD rats, particles with a diameter between 1.5 and 2 mm represent the cut-off for gastric emptying.
• Particles larger than 2 mm should be avoided in gastric emptying studies using intact particles in SD rats to ensure accurate results.