Effect of particle size on gastric emptying of enteric-coated granules in fasted beagle dogs: Relationship with interdigestive migrating motor complex

Abstract

This study investigates the particle size threshold at which the interdigestive migrating motor complex (IMMC) becomes active in gastric emptying for fasted beagle dogs. Enteric-coated granules containing cetirizine dihydrochloride (CET) were prepared in three particle sizes, 200, 660, and 1,200 µm (D50). To mark IMMC timing and water movement from the stomach, enteric-coated aspirin tablets and acetaminophen solution were used. To six fasted beagle dogs with 50 mL of acetaminophen solution was administered each granule size as a multiple-unit and a single enteric-coated aspirin tablet (3-period crossover study). No significant difference in pharmacokinetic parameters of CET after oral administration of different particle sizes was observed. However, the appearance time of CET in plasma with smaller granules (200 and 660 µm) was significantly faster than that of salicylic acid (a major metabolite of aspirin) in all dogs. In the case of the largest granules (1,200 µm), no significant time difference was observed in the appearance of both compounds in plasma. Furthermore, in two dogs, both compounds appeared at the same time, implying IMMC-regulated gastric emptying for the largest CET granules. These results support a particle size threshold between 660 and 1,200 µm for gastric emptying without IMMC action in fasted beagle dogs.