Physiological and Pharmaceutical Considerations for Rectal Drug Formulations

Abstract

Although the oral route is the most convenient route for drug administration, there are a number of circumstances where this is not possible from either a clinical or pharmaceutical perspective. In these cases, the rectal route may represent a practical alternative and can be used to administer drugs for both local and systemic actions. The environment in the rectum is considered relatively constant and stable and has low enzymatic activity in comparison to other sections of the gastrointestinal tract. In addition, drugs can partially bypass the liver following systemic absorption, which reduces the hepatic first-pass effect. Therefore, rectal drug delivery can provide significant local and systemic levels for various drugs, despite the relatively small surface area of the rectal mucosa. Further development and optimization of rectal drug formulations have led to improvements in drug bioavailability, formulation retention, and drug release kinetics. However, despite the pharmaceutical advances in rectal drug delivery, very few of them have translated to the clinical phase. This review will address the physiological and pharmaceutical considerations influencing rectal drug delivery as well as the conventional and novel drug delivery approaches. The translational challenges and development aspects of novel formulations will also be discussed.

Studies of physico-chemical and pharmaco-technological parameters of bioflavonoids diosmin and hesperidin

“…This scientific study should be planned on the study of indicators that will maximize the bioavailability of substances in the anorectal zone. To this end, studies should be conducted to establish solubility, distribution, moisture absorption and thermal stability [11].…”

Transmucosal drug administration as an alternative route in palliative and end-of-life care during the COVID-19 pandemic

“…It is approximately 15–20 cm in length. With the lack of villi or microvilli on the luminal surface, it has a relatively small surface area (200–400 cm 2 ) in contrast to the small intestine (~ 2,000,000 cm 2 ) for drug absorption [ 106 ]. The wall of rectum consists of a single layer of columnar epithelial cells together with the goblet cells.…”

“…The rectal mucus layer is around 150 μm thick [ 108 ] and it acts to lubricate and protect the rectal epithelium (e.g. during defecation) but at the same time it also presents a barrier for drug absorption [ 106 ]. The rectal fluid has a neutral pH of 7–8, which favours the absorption of drugs that are predominantly in their non-ionised form at this pH range.…”

“…4 ). The fate of the absorbed drug is dependent on the site where absorption occurs [ 106 ]. Drugs absorbed at the upper rectum enter the superior rectal vein which drains through the mesenteric and portal veins into the liver.…”

“…In contrast, drugs absorbed at the lower rectum enter the middle and inferior rectal veins which drain through the inferior vena cava directly into the systemic venous circulation, thereby avoiding first-pass metabolism. It has been reported that approximately 50% of the dose of a drug can bypass the liver [ 106 ]. Compared to other parts of the gastrointestinal tract, the rectum has a much lower enzymatic activity, hence rectal degradation of drug is also relatively low.…”