Colonic spread of three rectally administered mesalazine (Pentasa) dosage forms in healthy volunteers as assessed by gamma scintigraphy

Background: Rectal administration of enemas, foams and suppositories is the most efficient method of delivering locally-acting drugs to the distal colon, sigmoid colon and rectum. Healthy Volunteers provide an effective population to compare different formulations for rectal drug delivery. However, there is still only limited comparative information available on the dispersion of such dosage forms in human subjects, Therefore, the objective of this scintigraphic study was to compare colonic spread of an enema, a rectal foam and a suppository formulation in healthy volunteers. Methods: This was a randomized, crossover study in eight healthy male volunteers, Each received Pentasa rectal formulations as either a 100 mL suspension enema (1 g mesalazine), one actuation of a non-CFC propellant rectal foam (1 g mesalazine in 5 mL concentrate, expanding to 40 mL on actuation), or one suppository (1 g mesalazine) on three separate occasions. The spread of the radiolabelled formulations was assessed over a 4-h period by gamma scintigraphy. Results: The formulations were retained by all subjects for the whole of the 4-h imaging period, The enema spread to the splenic flexure in 7 out of 8 subjects, but was retained in the rectum and sigmoid colon in one individual, The foam spread as far as the descending colon in four subjects. In the remaining individuals the foam was retained in the rectum and sigmoid colon. The spread of the suppository was limited and confined to the rectum. Conclusions: The findings of this study are consistent with previous research and support the intended clinical uses of the enema, foam and suppository formulations to treat distal ulcerative colitis, proctosigmoiditis and proctitis, respectively. The results highlight the potential of gamma scintigraphy in providing in vivo 'proof of concept' data to help verify the targeting of pharmaceutical products to their intended site of delivery.