Spreading of rectal dosage forms

In order to treat the colon via the rectal route, rather than simply aiming for rectal absorption, the preparation must spread efficiently. This limits topical treatment of the colon to areas distal to the splenic flexure. A number of attempts have been made to increase penetration through the use of novel formulations, using scintigraphy to evaluate the distribution of the formulation.

Tukker et al studied the spreading of suppositories and the effect of added surfactant (Witepsol H-15) in recumbent dogs117. The addition of surfactants markedly increased the penetration into the colon. Similarly pre-administration of neostigmine, which increases colonic motility, markedly increased the spreading of the suppository (Figure 7.11).

The spreading behaviour of suppository bases and incorporated suspensions has also been studied in humans118. The bases, Witepsol H15 and Labrafil WL2514 were labelled by the incorporation of small amounts of iodine-123 labelled oily markers (arachis oil and Labrafil WL2700 respectively). The suspension consisted of micronized cationic exchange resin incorporated throughout the base at a disperse phase loading of 10% w/v. Most of the spreading of both base and suspension occurred in the first hour after administration, and the area of spreading was small, with a maximum of 8 to 10 cm. The time from defaecation to administration of the suppository appeared to affect the degree of spreading, with the greatest spreading occurring when defaecation occurred immediately prior to dosing119.

Disease activity in ulcerative colitis had no effect on the spreading behaviour of different volumes of mesalazine enemas, but the adminstered volume had a significant effect120. A 30 ml enema remained mainly in the sigmoid colon (99%), a 60 ml enema was distributed through the rectum (9%), the sigmoid (61%) and the descending colon (15%) and a 100 ml enema was distributed between the sigmoid (66%) and descending colon

Foam Solution

Figure 7.12 Spreading of liquid and foam enema after rectal administration

(25%). Consequently it appears that increasing the administered volume causes the dose to spread more effectively into the colon.

In an attempt to increase the penetration of small volumes of liquid, foam enemas have been studied121. However retrograde spreading of foams was lower than solution enemas, being limited to the sigmoid colon (Figure 7.12).

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