THE EFFECTS OF PHARMACEUTICAL EXCIPIENTS ON SMALL-INTESTINAL TRANSIT

1 The effect of three iso-osmotic pharmaceutical excipient solutions on gastrointestinal transit were investigated in eight healthy male volunteers. Each subject received 200 ml radiolabelled purified water, or a 200 ml solution of sodium acid pyrophosphate ((SAPP) 1.1 g/200 ml), mannitol (2.264 g/200 ml) or sucrose (4.08 g/200 ml) in a four way cross over design. On each of the study days the volunteers also received five 6 mm diameter non-disintegrating tablets. Dual isotope gamma scintigraphy was used to assess the transit behaviour of the tablets and solutions. 2 There were no significant differences between the gastric emptying times of the four solution formulations. Rapid gastric emptying was observed in all cases (mean t 50% varied from 11-14 min). 3 Small intestinal transit (SIT) times for the SAPP and mannitol solutions were reduced by 39 and 34%, respectively, when compared with the control solution (purified water = 240 min; SAPP = 147 min; mannitol = 158 min). The 95% confidence limits for the mean differences in SIT time between the control and SAPP solutions was 39-94-149 min, and 40-82-124 min between the mannitol and the control. Intestinal transit for the sucrose solution was similar to that for the control solution (sucrose = 229 min). 4 There were no significant differences in the transit times of the non-disintegrating tablet preparations, when co-administered with each solution. 5 The intestinal transit data for the SAPP and mannitol solutions demonstrate that excipients may alter gastrointestinal transit at low concentrations relevant to pharmaceutical formulation, and may therefore be a factor in reducing the absorption of certain drugs.