Solvent system effects on drug absorption.
The in situ rat gut technique was used to determine 14-C salicylic acid absorption from aqueous solutions containing 20% glycerol, 20% propylene glycol, 10% ethanol, and 20% polyethylylene glycols (PEG) 4000 and 6000. A phosphate buffer solution of salicylic acid served as a control. Observed rate constants for disappearance of activity from the gut are 0.031 min-1 for glycerol, 0.0327 min-1 for PEG 6000, 0.0395 min-1 for propylene glycol, 0.475 min-1 for polyethylene glycol 4000, 0.0558 min-1 for ethanol, and 0.0752 min-1 for the control. The rate of disappearance from the gut is significantly slower than control for 20% glycerol, PEG 4000 and PEG 6000 solutions (p less than or equal to 0.01). Activity disappears more rapidly from 10% ethanol solutions than from PEG 6000 and glycerol (p = 0.01). Water flux into and out of the intestinal lumen was estimated from tritiated inulin concentrations in the perfusate. A trend for increased loss of activity from ethanol and control solutions associated with net water efflux from the intestine was observed. These results suggest that the composition of drug delivery systems may significantly affect the absorption of drugs from solution.
D000818:Animals; D007408:Intestinal Absorption / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D012459:Salicylates / Q000378:metabolism; D012997:Solvents / Q000494:pharmacology*; D014867:Water / Q000378:metabolism
D004364:Pharmaceutical Preparations; D012459:Salicylates; D012997:Solvents; D014867:Water