Physiological Pharmaceutics

Colon and rectal drug delivery 151Colonic bacteria possess exocellular lipases which are able to hydrolyse fatty acidesters at the 1 and 3 positions of the triglyceride molecule. They also produce enzymescapable of metabolising long chain fatty acids. Approximately 25% of faecal fatty acids arehydroxylated by colonic bacteria, for example oleic acid is hydroxylated to formhydroxystearic acid. The presence of hydroxylated fatty acids in the colon has an inhibitoryeffect on colonic electrolyte and water transport, and at high concentrations they cause netsecretion of water and electrolytes, which results in diarrhoea and therefore a significantlyincreased colonic transit rate. Infusion of oleic acid (4.3 g per 100 ml) into the midascendingcolon accelerated colonic transit rate and defaecation when compared to acontrol infusion 12 .The microbial population exerts a profound effect on the structure and function ofthe digestive tract, as the morphology of the intestine of germ-free animals differsconsiderably from normal animals. Villi of the small intestine are remarkably regular, therate of epithelial cell renewal is reduced and, as one would expect, the number and size ofPeyer’s patches is reduced. The caecum of germ-free rats is roughly 10 times the size of thatin a conventional rat.Colonic motilityPatterns of motilityThe colon is an intermittently active organ and three patterns of motility are observed:(i) segmental contractions which chop and mix the contents, increasing contact withthe mucosa where absorption can occur.(ii) antiperistaltic contractions which propagate toward the ileum. These serve toretard the movement of contents through the colon, allowing additional opportunity forabsorption of water and electrolytes to occur. Peristaltic contractions, in addition to influxfrom the small intestine, facilitate movement of contents through the colon.(iii) mass movements constitute a type of motility not seen elsewhere in the digestivetube. They are also known also as giant migrating contractions; this pattern of motilityresembles a very intense and prolonged peristaltic contraction which strips an area of largeintestine clear of contents.Segmental activity consists of local contractions which are usually effected by circularmuscle and lead to the mixing of luminal contents, whereas propulsive activity is largely dueto contraction of longitudinal muscle. In the colon, the predominant activity is segmental,with the propulsive type of movement occurring infrequently (3–4 times daily in normals)(Table 7.2).Table 7.2 Patterns of colonic motility 13