Rectum delivery

All the above mentioned polymers have been evaluated mainly for application in the intestine. Finally, the last part of the gastrointestinal tract, the rectum should also be mentioned as a suitable site for delivery and fast absorption of therapeutics. Kim et al. [88] developed an in situ gelling and mucoadhesive acetaminophen liquid suppository prepared with poloxamers and sodium alginate. It was found that this particular formulation of acetaminophen in humans resulted in shorter T ax and higher maximum plasma concentrations of dmg (C ax) than the conventional acetaminophen suppositories. 

Drugs given into the rectum are usually wrapped up in some slow delivery matrix so that they are absorbed slowly. An exception is the antimicrobial metronidazole, which can be given through the rectum to achieve as high plasma concentrations as can be achieved with oral or even parenteral administration. 

The rectum has historically been an accepted site of drug delivery [1], Its principal applications have been for local therapy, e.g., hemorrhoids, and for systemic delivery of drugs, e.g., fever and pain. The rectal route can be an extremely useful route for delivery of drugs to infants, young children, and patients where difficulties can arise from oral administration... 

Human vagina is an S-shaped fibromuscular collapsible tube, 6-10 cm long, extending from cervix to uterus and located between the bladder and the rectum [1], It presents unique features in terms of secretions (pH and composition) and microflora, which must be considered during the development and the evaluation of vaginal drug delivery systems [2],... 

A therapeutic substance can be administered to a patient via a number of pathways. Oral delivery (by the mouth) was among the very first drug delivery methods used in the pharmaceutical industry [26]. Drugs may also be transferred to the alimentary channel via sublingual (under the tongue) or rectal (to the rectum) administration. 

Site-specific oral drug delivery requires spatial placement of a drug delivery device at a desired site within the GI tract. Although it is virtually possible to localize a device within each part of GI tract, the attainment of site-specific delivery in the oral cavity and the rectum is relatively easier than in the stomach and the small and large intestines. The latter requires consideration of both longitudinal and transverse aspects of GI constraints. Some of the potential CR and site-specific DDSs will be described. 

The smaller the drug molecule, the more readily it can be absorbed. For larger molecules, some type of facilitated transport or the use of penetration enhancers have been found to increase drug absorption from the rectum as well as from other delivery routes. 

Various formulation concepts have been introduced as potential ways to protect peptide and protein drugs from the hostile GI environment to increase their oral absorption such as use particulate drug carriers (microspheres, lipo-somes, and lectins), coadministration of enzyme inhibitors and absorption enhancers, use of chemical modification (prodrug), and site-specific delivery to the colon or rectum. Some of these approaches are discussed later. 

Peptidases such as aminopeptidases and diamino-peptidases are at lower concentrations in the colon than in the small intestine. However, it has been shown that prolyl endoprotease and collagenase activities are five to six times higher in the colon than in the small intestine. TRH is more readily hydrolyzed to deaminated TRH in colonic homogenates compared with small intestine and rectum. Therefore, peptide drugs that are substrates for prolyl endoprotease and collagenase will likely be degraded in the colon and may not be suitable for colon delivery. 

Rectal delivery, depending on the position of the dosage form in the rectum, can be used to target either the systemic circulation or the liver. For systemic targeting, the dosage form should be placed and located directly behind the internal rectal sphincter, whereas targeting the liver requires the dosage form to be placed in the ampulla recti (about 12-15 cm up the rectum) (50). 

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