Physiological Pharmaceutics

Colon and rectal drug delivery 149Table 7.1 Comparison of the environment in different parts of the gastrointestinal tracthormonal and neural mechanisms on colonic motility, the major control for the transit ofluminal contents is exerted by the smooth muscle itself.Colonic environmentThe colonic environment markedly differs from other parts of the gastrointestinal tract asillustrated in Table 7.1. The absorptive capacity of the colon is much less than that of thesmall intestine, due mainly to the reduced surface area. The mucosal surface of the colonis similar to that of the small intestine at birth, but rapidly changes by losing villi leavinga flat mucosa with deep crypts. As the gut ages there is a decrease in the number of nongobletcrypt cells and this is related to an increase in faecal water 7 .Water and electrolytesThe colon has a very high absorptive capacity; for every 2 litres of water entering the colon,the residual water in the stools will be less than 200 ml. The flow of chyme from the ileumto the colon in healthy human beings is 1–2 litres.h -1 . The colon is capable of absorbing upto 4 L of water per day and can withstand an infusion rate of 6 ml.min -1 before there is anyincrease in faecal water 8 9 . The large capacity of the colon to absorb fluid may, however, beoverwhelmed by a large fluid input and unabsorbed solutes, such as bile acids, fatty acids,or carbohydrates can also impair this adaptive capacity, possibly resulting in diarrhoea.Absorption of water and sodium is negligible from the rectum. Solids are consolidated to200–300g of wet material which is equivalent to 30–40 g of dry matter, which is mainlybacterial in origin but contains undigested organic matter and fibre.The colon is responsible for the absorption of sodium ions, chloride ions and waterfrom the lumen in exchange for bicarbonate and potassium ions. The absorption of sodiumis an active process and involves its diffusion across the apical membrane of epithelial cellsvia water filled channels. Sodium absorption in the colon is enhanced by the hormonealdosterone. A sodium-potassium exchange pump system in the baso-lateral membrane thenmoves sodium against steep concentration (14 mM to 140 mM) and electrical (-30 mV to+20 mV) gradients into the intercellular space. This movement of sodium creates an osmoticgradient which causes a net movement of water from the colonic lumen via the epithelialcells, through the tight junctions between epithelial cells into the intercellular spaces.In healthy individuals, approximately 10 mEq of potassium enters the colon each daywhilst 5 to 15 mEq are lost in the faeces during the same time period. Potassium secretionis determined by the luminal concentration of potassium, with concentrations of below 15mEq leading to net secretion. This is accomplished by passive movement of potassium ionsalong an electrochemical gradient from plasma to lumen, and is facilitated by the tightjunctions between epithelial cells which are highly permeable to potassium ions. The