THE EFFECTS OF PHARMACEUTICAL EXCIPIENTS ON SMALL-INTESTINAL TRANSIT

1 The effect of three iso-osmotic pharmaceutical excipient solutions o n gastrointestinal transit were investigated in eight healthy male vol unteers. 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 cr oss over design. On each of the study days the volunteers also receive d five 6 mm diameter non-disintegrating tablets. Dual isotope gamma sc intigraphy was used to assess the transit behaviour of the tablets and solutions. 2 There were no significant differences between the gastri c emptying times of the four solution formulations. Rapid gastric empt ying was observed in all cases (mean t 50% varied from 11-14 min). 3 S mall intestinal transit (SIT) times for the SAPP and mannitol solution s were reduced by 39 and 34%, respectively, when compared with the con trol solution (purified water = 240 min; SAPP = 147 min; mannitol = 15 8 min). The 95% confidence limits for the mean differences in SIT time between the control and SAPP solutions was 39-94-149 min, and 40-82-1 24 min between the mannitol and the control. Intestinal transit for th e sucrose solution was similar to that for the control solution (sucro se = 229 min). 4 There were no significant differences in the transit times of the non-disintegrating tablet preparations, when co-administe red with each solution. 5 The intestinal transit data for the SAPP and mannitol solutions demonstrate that excipients may alter gastrointest inal transit at low concentrations relevant to pharmaceutical formulat ion, and may therefore be a factor in reducing the absorption of certa in drugs.