The effect of polyethylene glycol 400 on gastrointestinal transit: implications for the formulation of poorly-water soluble drugs.
OBJECTIVE
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.
Basit
A W
AW
Department of Pharmaceutics, The School of Pharmacy, University of London, UK. abdul.basit@ulsop.ac.uk
Newton
J M
JM
Short
M D
MD
Waddington
W A
WA
Ell
P J
PJ
Lacey
L F
LF
D000328:Adult; D002214:Capsules; D002432:Cecum / Q000000981:diagnostic imaging / Q000378:metabolism; D004064:Digestive System / Q000000981:diagnostic imaging / Q000378:metabolism; D005079:Excipients; D005746:Gastric Emptying / Q000187:drug effects; D005753:Gastric Mucosa / Q000378:metabolism; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007421:Intestine, Small / Q000000981:diagnostic imaging / Q000378:metabolism; D007553:Isotope Labeling; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011877:Radionuclide Imaging; D012995:Solubility; D013270:Stomach / Q000000981:diagnostic imaging
D002214:Capsules; D005079:Excipients; D004364:Pharmaceutical Preparations; D011092:Polyethylene Glycols