Enemas absorption active substance

The onset of action with enemas is often faster than with suppositories and a larger part of the rectum and colon can be used for absorption. The latter is relevant for a local action. The chemical form of the active substance, the choice of the solvent and the pH of the preparation are important criteria. 

Glafenine has a solubility in water of 1 in 60,000 at pH 7. The rectal absorption of glafenine from an aqueous micro-enema, and of glafenine hydrochloride from a fatty suppository is extremely slow and incomplete, due to the low solubility of glafenine at the pH in the rectum [16]. Therefore this active substance is not effective after rectal administration, although glafenine suppositories were commercially available in the past century. On the contrary, for example, the solubility of phenobarbital in water of 1 in 1,000 is sufficient for rectal administration. 

Rectal absorption depends on solubility and lipophilicity of the active substance (see further Sect. 16.1.5), and is influenced therefore by volume, pH, and buffering capacity of the enema (see Sects. 11.3 and 16.2.4). 

The volume of enemas may vary from a few millilitres (micro-enema) to more than 100 mL, mainly depending on the intended effect systemic or local. For large-volume enemas water is commonly used and a water-soluble form of the active substance is preferred. The solubility may be increased by addition of co-solvents, to be applied in small volume enemas. If a soluble active substance or an adequate co-solvent cannot be found, a suspension may be prepared. If this is also not an option, a lipophilic vehicle may be chosen. Choice of pH depends on the chosen form of the active substance and is important for the absorption. Excipients may be added to correct the osmotic value, to increase the viscosity, to prevent oxidation or for preservation. 

The influence of particle size on the absorption rate from aqueous suspension enemas has probably never been investigated. Dissolution of the active substance is assumed to increase with decreasing particle size (see Sect. 29.2.1). For the requirements on particle size for a stable suspension enema reference is made to Sects. 29.2 and 29.3 as well as to Sect. 5.10 because of similarity with oral suspensions. A particle size of maximal 180 pm generally satisfies. Suspension stability is less important than for oral use since an enema is dispensed in single-dose containers. However,... 

For enemas with an oily vehicle, the considerations regarding solubility of active substance and choice of particle size resemble those for fatty suppositories (see Sect. 11.4.1). The process of release and absorption of the active substance is also largely comparable to that of fatty suppositories just the melting step is not necessary. 

The pH of enemas is important for stabihty and absorption of the active substance. Regarding irritation, a pH-value between 4 and 10 is acceptable for an enema up to 20 mL [54], but preferably the pH should approach the physiological value (pH 7-8). In particular if the active substance is a weak acid or a weak base the pH may be adjusted to shift the equihbrium to the unionised form. Absorption of an active substance appears to be better from a buffered solution than from an tmbuffered solution with equal pH, so adjusting is best done by a buffer [55]. A phosphate buffer is frequently used for this purpose. 

Rectal solutions have water or oil as a vehicle. If necessary to enhance the solubility of poorly soluble active substances, aqueous rectal solutirms may contain cosolvents, such as ethanol and propylene glycol. However, cosolvents and surfactants should only be used in limited amounts because of the potential irritation and the defecation reflex they may cause. For the rectal absorption of active substances from enemas the same mechanisms as for suppositories apply. A major advantage of a rectal solution over a suppository may be the fact that the active substance is already in a dissolved state which may increase the absorption rate. Increasing the volume of a rectal solution to dissolve a poorly water-soluble active substance will enhance the dissolution rate and thereby increase the absorption rate. Because of the higher volume more active substance will be dissolved and the membrane surface over which absorption occurs, is increased as well. 

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