Gastrointestinal transit of pellets in rats: effect of size and density

Gastrointestinal distribution kinetics of a large amount (0.5-1 g) of three types of non-disintegrating pellets which had the same size (S1, 710-1000 micrometers) but different densities (D1, 0.9 and D2, 1.5 g cm-3), or which had the same density (D1) but different diameters (S1 and S2, 1250-1600 micrometers) were examined in fed rats. The percentage of pellets remaining in the stomach, small gut, caecum and colon was measured at suitable intervals. Whatever the size of the pellets, the heavier the density, the longer the gastric emptying (2.1 h for D2-S1 instead of 1.3 h for D1-S1 and 0.7 h for D1-S2). The small gut transit time was not influenced by density but was slightly prolonged by size: 3.3 h for D1-S2 instead of 2.6 h for D1-S1 and D2-S1. Conversely, the gastrocolonic transit time was widely influenced by density (13.5 h for D2-S1) and somewhat by size (8.2 h for D1-S2 and 4.5 h for D1-S1). This delays were proportional to caecal residence time in the large, sacculated and derivated caecum of rats. In order to use the rat as an experimental model for pharmaceutical pellets, those results should have implication for the design of dosage forms, particularly those for controlled or timed release or those for targeted release at specific positions in the gastrointestinal tract.