Rectal delivery

A review of GI transit and oral drug absorption can be organized in many ways, but a logical sequence is to start at the top and work down. In this review, techniques to study buccal and rectal delivery will not be covered, but a detailed description of these is available in a recent book (1). 

Figure 5 Moraxen rectal delivery systems with 35, 50, 75, 100 and 125 mg based on the Hycore -R technology.

Figure 6 Moraxen rectal delivery system. Comparative steady-state simulation of morphine plasma levels after single daily rectal administration of Moraxen with 100 mg morphine compared with twice-daily 50 mg morphine (OSRM) in an oral prolonged-release formulation. The simulation is based on the plasma levels from a single-dose study.

Within the last 10, years several new compounds were launched in the field of non-steroidal antiinflammatory drugs (NSAIDs) with a clear focus on cyclooxygenase type 2 selective compounds. In the field of opioids on the other hand no new drugs have passed phase III clinical trials. In this field innovation has been achieved through new pharmaceutical formulations of known drugs such as transdermal systems, e.g. buprenorphine patch, transmucosal systems, e.g. fentanyl lollipop, or rectal delivery systems containing e.g. morphine. These were developed in order to reduce opioid side effects, but also to overcome pharmacokinetical limitations, in particular to prolong compliance and duration of action. 

Bundgaard, H., E. Jensen, E. Falch, and S. B. Pedersen. 1990. Allopurinol prodrugs. V. V feter-soluble N-substituted (aminomethyl)benzoyloxymethyl allopurinol derivatives for parenteral or rectal delivery. 

Many drugs can now be delivered rectally instead of by parenteral injection (intravenous route) or oral administration. Generally, the rectal delivery route is particularly suitable for pediatric and elderly patients who experience difficulty ingesting medication or who are unconscious. However, rectal bioavailabilities tend to be lower than the corresponding values of oral administration. The nature of the drug formulation has been shown to be an essential determinant of the rectal absorption profiles. The development of novel absorption enhancers with potential efficacy without mucosal irritation (low toxicity) is very important. The delivery of peptide and protein drugs by the rectal route is currently being explored and seems to be feasible. 

De Leede, L.G.J., et al. 1982. Zero-order rectal delivery of theophylline in man with an osmotic... 

Matsuda, H., and Arima, H. 1999. Cyclodextrins in transdermal and rectal delivery. Adv Drug Deliv Rev 36 81. 

Inhibitory Effects of Cyclodextrins of Drug Irritancy in Rectal Delivery.157... 

Many reports have indicated the findings that the effects of CyDs on the rectal delivery of drugs depend markedly on vehicle type (hydrophilic or oleaginous), physicochemical properties of the complexes, and an existence of tertiary excipients such as viscous polymers. The enhancing effects of CyDs on the rectal absorption of lipophilic drugs are generally based on the improvement of the release from vehicles and the dissolution rates in rectal fluids, whereas those of CyDs on the rectal delivery of poorly absorbable drugs such as antibiotics, peptides,... 

Arima, H., T. Rondo, and T. Irie. 1992. Use of water-soluble (3-cyclodextrin derivatives as carriers of anti-inflammatory drug biphenyl-acetic acid in rectal delivery. Yakugaku Zasshi 112 65. 

Murakami, T., et al. 1981. Studies on absorption promoters for rectal delivery preparations. I. Promoting efficacy of enamine derivatives of amino acids for the rectal absorption of (3-lactam antibiotics in rabbits. Chem Pharm Bull 29 1998. 

Chapter 8 Cyclodextrins and Other Enhancers in Rectal Delivery.147... 

N. Bodor, T. Murakami, and W.-M. Wu, Soft drugs. 18. Oral and rectal delivery of loteprednol etabonate, a novel soft corticosteroid, in rats-for safer treatment of gastrointestinal inflammation, Pharm. Res. 12 869 (1995). 

Before reaching the target organ, drugs must pass through the liver. This can be avoided by direct intravenous delivery of drugs. Optimized oral or rectal delivery also avoids the liver passage. 

Oral transmucosal devices, such as sprays, tablets or patches, are also simple for the patient to use and might be expected to be more acceptable to the patient than the use of pessaries or suppositories for the intravaginal and rectal delivery routes respectively. 

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