Figure 7.6 Transit of a large non-disintegrating unit and pellets through the gastrointestinal tract—a scintigraphic study

Figure 7.6 Transit of a large non-disintegrating unit and pellets through the gastrointestinal tract—a scintigraphic study compared to 5mm particles, which became significant following laxative administration. Selective retention of small particles is known as colonic sieving and may be important in drug delivery, although the upper cut-off size limit for retention of particles has yet to be established. The sieving behaviour in disorders such as ulcerative colitis, where the degree of haustration is reduced, may influence the upper size limit for retention.

If units become too large, they can have prolonged transit due to periods of stasis at the ileo-caecal junction, hepatic and splenic flexures. Care should be taken when using large rigid units to study drug absorption from the colon, since an unphysiologically long colonic transit time would suggest an erroneously long time for drug absorption. The absorption times would then be significantly reduced when the drug was administered in a more normally sized dosage form.

The sieving effect causes dispersible dosage forms such as pellets to become widely distributed in the colon, whilst large single units or fragments of tablets travel rapidly through the colon ahead of the smaller pellets (Figure 7.7). This phenomenon is related to the observation that batches of markers of increasing sizes given with successive meals become interdispersed within the large intestine80 which could be explained by the larger particles moving fastest. In the descending colon, the particles come together before defaecation. This data suggests that optimisation of drug delivery to the proximal colon may be achieved with a multiparticulate preparation which remains intact for approximately the first 5 hours after administration to the fasted patient. This would allow time for gastric emptying and transit through the small intestine. The drug preparation should then disperse allowing release of the material over the following 10 to 12 hours in the ascending and transverse colon. Extending the release profile over a longer period would not be an added advantage due to the variability of excretion patterns and the slower diffusion through consolidating faecal material.

Dose 60" Remaining

80 n

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