The use of pharmacoscintigraphy to focus the development strategy for a novel 5-ASA colon targeting system (“TIME CLOCK®” system)

In the early stages of product development for novel colonic delivery systems, considerable time can be lost in establishing the likely potential of any given research strategy because of a lack of suitable in vitro or animal models. We therefore report on the utility of pharmacoscintigraphic evaluation in man to gauge the suitability of three prototype enteric coated 5-ASA “TIME CLOCK®” systems for possible development as front line therapies for treatment of inflammatory bowel disease. The clinical investigation involved the simultaneous assessment of transit/disintegration using scintigraphic imaging and drug absorption via traditional pharmacokinetic evaluation, for the three formulations (20%, 35% and 50% w/w hydrophobic coating) in a group of eight healthy volunteers. Initial tablet disintegration occurred at 5.91±1.47 h post-dose, 8.85±0.90 h post-dose and 12.03±1.25 h post dose for the 20%, 35% and 50% formulations, respectively. There was a clear differentiation between the three prototype 5-ASA “TIME CLOCK®” formulations in terms of in vivo lag time, anatomical location of disintegration, and subsequent 5-ASA absorption. The pharmacoscintigraphic findings provide “proof of concept” data for the colonic delivery of 5-ASA using enteric coated “TIME CLOCK®” technology and help focus the development strategy for subsequent clinical studies in the patient population.