The effect of polyethylene glycol 400 on gastrointestinal transit: Implications for the formulation of poorly-water soluble drugs

Purpose. To assess the effect of polyethylene glycol 400 (PEG 400), a pharm aceutical excipient frequently employed to enhance the solubility and bioav ailability of poorly water-soluble drugs, on the gastrointestinal transit o f liquid and pellet preparations in human subjects using gamma scintigraphy . Methods. Ten, healthy male volunteers each received, on separate occasions, a liquid preparation consisting of 150 ml orange juice (control) or 150 ml orange juice containing 10 g PEG 400 (test). Nondisintegrating pellets of size 1.4-1.7 mm, encapsulated within a hard gelatin capsule, were simultane ously administered on both occasions to act as a marker for solid dosage fo rm transit. The liquid and pellet preparations were radiolabelled with In-1 11 and Tc-99m respectively thus enabling their positions within the gastroi ntestinal tract to be followed using a gamma camera. Results. Rapid liquid emptying from the stomach was observed. with no signi ficant difference noted in the gastric residence times of the two preparati ons. Caecum arrival times for the liquid preparations were significantly di fferent by virtue of their differential rates of transit through the small intestine. The mean small intestinal liquid transit time for the control pr eparation was 236 min whereas the corresponding value for the PEG 400-conta ining test preparation was 153 min. This 35% reduction in transit time was attributed to the presence of PEG 400. Pellet transit was largely unaffecte d by the presence of PEG 400. Conclusions. These findings clearly demonstrate that PEG 400 has a marked a ccelerating effect on small intestinal liquid transit, which in turn has im plications for the formulation of poorly water-soluble drugs with PEG 400.