THE USE OF PHARMACOSCINTIGRAPHY TO FOCUS THE DEVELOPMENT STRATEGY FORA NOVEL 5-ASA COLON TARGETING SYSTEM (TIME CLOCK(R) SYSTEM)

In the early stages of product development for novel colonic delivery systems, considerable time can be lost in establishing the likely pote ntial of any given research strategy because of a lack of suitable in vitro or animal models. We therefore report on the utility of pharmaco scintigraphic evaluation in man to gauge the suitability of three prot otype enteric coated 5-ASA. ''TIME CLOCK(R)'' systems for possible dev elopment as front line therapies for treatment of inflammatory bowel d isease. The clinical investigation involved the simultaneous assessmen t of transit/disintegration using scintigraphic imaging and drug absor ption via traditional pharmacokinetic evaluation, for the three formul ations (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(R)'' f ormulations in terms of in vivo lag time, anatomical location of disin tegration, 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(R)'' technology and help foc us the development strategy for subsequent clinical studies in the pat ient population. (C) 1997 Elsevier Science B.V.