Physiological Pharmaceutics

Colon and rectal drug delivery 167Figure 7.10 Structure and perfusion of the rectumDosage forms for rectal deliveryDrugs can be administered in several formulations via the rectal route. Suppositories arenormally either solid suspensions or solid emulsions, whereas rectally administered gelatincapsules can contain liquid formulations. Micro-enemas have a volume of between 1 and20 ml, and macro enemas 50 ml or more, both of which may be administered as eithersolutions or suspensions. The suspension suppository is the most widely used formulation,and it has been demonstrated that the release characteristics are dependent uponphysiological factors, physicochemical properties of the drug, the suppository base and localenvironment within the rectum. In general, aqueous solutions of drugs are absorbed morequickly from the rectal route than the oral route, but absorption is usually slower with nonaqueousformulations, due to the limited amount of water available for drug dissolution.There has been some work exploring the use of controlled release to the rectum, toachieve prolonged and sustained drug delivery. The studies were performed using anosmotically driven device with zero-order release characteristics. It appears to be apromising delivery system for drugs such as nifedipine which effectively reduced bloodpressure without the unwanted side effect of increased heart rate 115 . Hydrogel systems withnear zero-order delivery have also been used to deliver morphine intrarectally 116 .Adjuvants and enhancersTransport from the rectal epithelium primarily involves two transport processes:paracellular and transcellular routes. As in other parts of the gut, the opening of tightjunctions by absorption enhancers has been extensively investigated. Putative enhancersinclude enamine derivatives, salicylates, calmodulin inhibitors, surfactants, chelating agents,fatty acids and lectins. It is generally agreed that the rectum is potentially an important route