Absorption, drug from rectal cavity

The absorption of drugs from the rectal [32] cavity has been studied in some detail. Muranishi et al. [34] have shown that a significant increase in the absorption and lymphatic uptake of soluble and colloidal macromolecules can be achieved by pretreating the rectal mucosal membrane with lipid-nonionic surfactant mixed micelles. They found no evidence of serious damage of the mucosal membrane. Davis [30] suggested that the vaginal cavity could be an effective delivery site for certain pharmaceuticals, such as calcitonin, used for the treatment of postmenopausal osteoporosis. 

The aminoglycosides are highly polar and, thus, poorly absorbed from the gastrointestinal (GI) tract. Instillation of these drugs into body cavities with serosal surfaces may result in rapid absorption and unexpected toxicity (e.g., neuromuscular blockade). Toxic levels also may result from sustained topical application to large wounds, bums, or cutaneous ulcers, particularly with renal insufficiency. Long-term oral or rectal administration of aminoglycosides may result in accumulation to toxic concentrations in patients with renal impairment. 

The pharmacist should have anticipated the bio-pharmaceutical consequences of the physico-chemical properties of oxcarbazepine. The drug is classified as a Class II substance for oral application. Logically, lack of adequate solubility is even more evident for the rectal administration as the volume of rectal fluid is limited (see Table 17.1). With an aqueous solubility of approximately 300 mg/L, the solubUity of the substance in the lipophilic base of the suppositories would certainly not be higher than 9.5 mg/mL (being a direct consequence of the value of the log P = 1.5 of oxcarbamazepine). This means that oxcarbazepine is not dissolved in the lipid but dispersed as crystals, which settle from the molten suppository once introduced in the rectal cavity. The amount of rectal liquid is limited and therefore a saturated solution will exist which involves only less than 1 mg dissolved oxcarbamazepine. Low solubility yields a low concentration and hence a low driving force for diffusion to occur. As a consequence, the rate of absorption is relatively low. This slow release may lead to hardly any uptake, due to defecation within several hours after insertion. 

Suppository is solid-like preparation made from drug and suitable bases for cavity administration. When inserted into cavities, they melt or soften, after which drug dissolution and absorption result in local or systemic effect. Whin rectal suppository is a common form which is usually used as laxatives. Administrated by rectum mucosa, suppositories possess many advantages compared with oral route. Firstly, it is a convenient administration way for infants or patients suffering from vomiting or gastrointestinal disturbances. 

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