Drug absorption rectal suppositories

TABLE 7.1 Influential Factors on Rectal Drug Absorption from Suppository ... 

The hepatic first-pass effect can be avoided to a great extent by use of sublingual tablets and transdermal preparations and to a lesser extent by use of rectal suppositories. Sublingual absorption provides direct access to systemic—not portal—veins. The transdermal route offers the same advantage. Drugs absorbed from suppositories in the lower rectum enter vessels that drain into the inferior vena cava, thus bypassing the liver. However, suppositories tend to move upward in the rectum into a region where veins that lead to the liver predominate. Thus, only about 50% of a rectal dose can be assumed to bypass the liver. 

The physicochemical properties of the drug molecules and the formulation can also influence rectal drug absorption (Table 7.1). Crucial parameters in this regard include drug concentration, molecular weight, solubility, lipophilicity, pKa, surface properties, and particle size [12]. In addition, formulation properties such as the nature of the suppository base material may play a critical role in regulating drug absorption. 

Takahashi, H., et al. 1997. The enhancing mechanism of capric acid (CIO) from a suppository on rectal drug absorption through a paracellular pathway. Biol Pharm Bull 20 446. 

The rectal milieu is quite constant as its pH is about 7.5, and the temperature is usually 37°C. It is normally empty and the pressure varies between 0 and 50 cm. This makes this route suitable for the (controlled) delivery of drugs by applying adequate (controlled release) dosage forms such as osmotic pumps and hydrogels, since the classical suppositories are, in general, not the most suitable dosage form to achieve a reproducible rate and extent of drug absorption. 

There are at least two common problems that can lead to drug loss following rectal administration. First, for effective absorption, the dosage form must be retained in the rectum. Thus if the dosage form or parts thereof are lost prematurely from the rectum, drug absorption will be substantially reduced. A study with children showed that when thiopentone suppositories were voided within 40 min, an effective plasma level was maintained for less than 2 h, whereas when the suppositories were retained, an effective level was maintained for about 24 h. 

Other routes of administration arc theoretically possible such as rectal route (rectal capsules and rectal suppositories) for drugs having systemic effects such a.s sedatives, tranquilizers, and analgesics topical route (patchs) for drug absorption (hormones or nicotine) into the systemic circulation parenteral route (administration of parenteral suspensions or implantation of compressed pellets). 

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. 

Rectal suppositories containing volatile, lipophylic drugs /i e essential oils, terpenoids/ have certain disadvantages that need to be reduced Neither the physical-mechanical properties of these suppositories nor the stability and rectal absorption of their active ingredients are satisfactory ... 

This model is representative for the conditions described in the previous section, except for the mode of administration which can be oral, rectal or parenteral by means of injection into muscle, fat, under the skin, etc. (Fig. 39.7). In addition to the central plasma compartment, the model involves an absorption compartment to which the drug is rapidly delivered. This may be to the gut in the case of tablets, syrups and suppositories or into adipose, muscle or skin tissues in the case of injections. The transport from the absorption site to the central compartment is assumed to be one-way and governed by the transfer constant (Fig. 39.7a). The linear differential model for this problem can be defined in the following way ... 

Rectal Administration. The administration of drugs by a solid rectal dosage form (i.e., suppositories) results in a wide variability in the rate and extent of absorption in children [79]. This fact, coupled with the inflexibility of a fixed dose, makes this a route that should not be promoted for pediatric patients. At least one death involving a 7-month-old infant can be directly attributed to the use of solid rectal dosage form of a therapeutic dose of morphine [80]. 

Schmitt M, Guentert TW. Influence of the hydrophilicity of suppository bases on rectal absorption of carprofen, a lipophilic nonsteroidal anti-inflammatory drug. J Pharm Sci 1990 79(4) 359-363. 

Lysergic acid is a well known component especially as its amide derviative - lysergic acid diethyl amide (LSD) - to be considered in the next section on CNS drugs. Today ergotamine can be used in the treatment of chronic migraine headache although its side effects do not make it an appropriate prophylactic. It is usually compounded with caffeine and administered orally, by inhalation or suppository. The caffeine increases oral and rectal absorption of the ergotamine. Oral dose is 2 mg at onset and 2 mg at 30 minute intervals up to 6 mg with no more than 10 mg administered per week. 

Watanabe, Y., et al. 1992. Absorption enhancement of polypeptide drugs by cyclodextrins. I. Enhanced rectal absorption of insulin from hollow-type suppositories containing insulin and cyclodextrins in rabbits. Chem Pharm Bull 40 3042. 

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