Drug Delivery

A wide range of colonic transit times must be taken into consideration during the design of drug delivery systems. Rapid transit will allow little time for the drug to be released before the dosage form is excreted, whilst prolonged colonic residence may result in the accumulation of drug from multiple doses.

After the hepatic flexure, the consolidation of faecal matter gradually increases the viscosity of the luminal contents. This results in increasing difficulty of drug diffusion to the absorbing membrane. Only the ascending colon is sufficiently fluid to present a favourable environment for drug absorption. Absorption of even the most water-soluble drugs is reduced after the mid-transverse colon, due to the lack of water. For example, ciprofloxacin demonstrates a clear reduction in drug uptake with a more distal delivery69. On rare

Figure 7.5 Plasma concentration-time profiles for oxprenolol delivered from an Oros® device in an individual with a short (top diagram) and long (bottom diagram) colon transit time

Figure 7.5 Plasma concentration-time profiles for oxprenolol delivered from an Oros® device in an individual with a short (top diagram) and long (bottom diagram) colon transit time occasions, drug absorption can be seen from the distal regions due to the drug affecting the fluidity of the contents of the transverse and descending colon.

Current knowledge suggests that it is possible to optimise delivery systems for topical release of drugs to the colon, since transit through the small intestine is relatively predictable and independent of diet. The major problems for colonic absorption are reduced surface area, wider lumen, sluggish movement, low volume of available dissolution fluid and the reduced permeability of the colonic epithelium to polar compounds. Thus it would be expected that the absorption of most drugs from the colon would be slower than from the small intestine. This is balanced by the slower transit through the colon. The potential of the colon as an area for drug absorption is illustrated in Figure 7.5, which shows the plasma concentration-time profiles of oxprenolol delivered in an Oros® device for two individuals with differing colonic transit times. The effect of the extended colon residence on the plasma drug concentration is clearly illustrated. An additional advantage for colonic delivery may lie in the much lower activity of proteinases in the colon, which is 20-60 fold less than in the small intestine, suggesting that absorption of labile peptides might be possible. Achieving therapeutically relevant doses of proteins and peptides when administered via the colon still remains a major challenge.

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