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Purpose: The aim of the study was to investigate the effect of different concentrations of polyethylene glycol 400 (PEG 400) on liquid transit through, and ranitidine absorption from, the gastrointestinal tract., Methods: Six healthy male volunteers received, on four separate occasions, 150 mL water containing 150 mg ranitidine and either 0 (control), 1,2.5, or 5 g PEG 400. The solutions were radiolabeled with technetium-99m to allow their gastrointestinal transit to be followed using a gamma camera. Urine samples were collected over a 24-h period to assess the amount of ranitidine excreted and hence absorbed., Results: No significant differences in gastric emptying were noted between the four solutions. In contrast, the presence of 1, 2.5, and 5 g PEG 400 reduced the mean small intestinal transit times of the solutions by 9, 20, and 23%, respectively, against the control. In terms of drug absorption, the mean cumulative amount of ranitidine excreted was reduced by 38% in the presence of both 2.5 and 5 g PEG 400, although it was significantly increased by 41% in the presence of 1 g PEG 400., Conclusions: The results show that low concentrations of PEG 400 enhance the absorption of ranitidine possibly via modulation of intestinal permeability, while high concentrations have a detrimental effect on ranitidine absorption presumably via a reduction in the small intestinal transit time.

Purpose: To investigate the effect of co-administered polyethylene glycol 400 (PEG 400), a pharmaceutical excipient previously shown to accelerate small intestinal transit, on the absorption characteristics of ranitidine from the gastrointestinal tract., Methods: Ten healthy male volunteers each received, on two separate occasions, an immediate-release pellet formulation of ranitidine (150 mg) encapsulated within a hard gelatin capsule and a liquid preparation consisting of 150 ml orange juice (control) or 150 ml orange juice containing 10 g PEG 400 (test). The liquid preparations were also radiolabelled with indium-III to allow their transit through the gastrointestinal tract to be followed using a gamma camera. On a further occasion an intravenous injection of ranitidine (50 mg) was administered. Blood samples were taken over a 12 h period on each study day to allow a ranitidine plasma and subsequent absorption rate profile to be generated for each oral formulation. Urine was collected for 24 h and assessed for PEG 400 concentration., Results: The absolute bioavailability of ranitidine from the pellet formulation was significantly reduced by 31% (from 51% to 35%) and small intestinal liquid transit time was significantly shortened by 37% (from 226 min to 143 min) as a consequence of PEG 400 in the test preparation. PEG 400 also affected the rate of ranitidine absorption, with major differences noted in the mean absorption time and Cmax parameters. The appearance of double peaks were less evident in the ranitidine pharmacokinetic profiles in the presence of PEG 400, and little or no correlation was observed between the absorption of ranitidine and PEG 400., Conclusions: These results clearly demonstrate that PEG 400 adversely influences the gastrointestinal absorption of ranitidine. This in turn has ramifications for the use of PEG 400 as a pharmaceutical excipient in oral formulations.

Purpose: To assess the effect of polyethylene glycol 400 (PEG 400), a pharmaceutical excipient frequently employed to enhance the solubility and bioavailability of poorly water-soluble drugs, on the gastrointestinal transit of 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). Non-disintegrating pellets of size 1.4-1.7 mm. encapsulated within a hard gelatin capsule, were simultaneously administered on both occasions to act as a marker for solid dosage form transit. The liquid and pellet preparations were radiolabelled with 111In and 99mTc respectively thus enabling their positions within the gastrointestinal tract to be followed using a gamma camera., Results: Rapid liquid emptying from the stomach was observed, with no significant difference noted in the gastric residence times of the two preparations. Caecum arrival times for the liquid preparations were significantly different by virtue of their differential rates of transit through the small intestine. The mean small intestinal liquid transit time for the control preparation was 236 min whereas the corresponding value for the PEG 400-containing test preparation was 153 min. This 35% reduction in transit time was attributed to the presence of PEG 400. Pellet transit was largely unaffected by the presence of PEG 400., Conclusions: These findings clearly demonstrate that PEG 400 has a marked accelerating effect on small intestinal liquid transit, which in turn has implications for the formulation of poorly water-soluble drugs with PEG 400.