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Legen, Igor; Kračun, Matjaž; Salobir, Mateja; Kerč, Janez
International journal of pharmaceutics, 02/2006, Letnik: 308, Številka: 1Journal Article
The aim of the present study was to evaluate different pharmaceutically acceptable excipients as permeation enhancers for a low permeability drug, amoxicillin. As a model for the intestinal epithelium excised rat jejunum, mounted in side-by-side diffusion cells, was used. Amoxicillin was actively transported across the intestine in the serosal-to-mucosal direction, but only if glucose was present at the mucosal side. This effect of glucose was abolished by a multridrug resistance associated protein (MRP) inhibitor benzbromarone (0.04 mM), but not by verapamil (0.2 mM). Among the tested pharmaceutically acceptable excipients only sodium lauryl sulfate (0.2 mg/ml) increased the permeability of amoxicillin in the mucosal-to-serosal direction, which was accompanying with the abolishment of the secretory oriented transport of amoxicillin. Other excipients (0.072 mg/ml Pluronic F68, 0.2 mg/ml Lutrol F127, 0.2 mg/ml Cremophor EL or 0.2 mg/ml Carbopol 934) have no influence on the permeability of amoxicillin. The effect of sodium lauryl sulfate on the active secretion of amoxicillin was mainly attributed to the reversible cellular ATP depletion. We concluded that sodium lauryl sulfate can be considered as a relatively safe permeation enhancer for amoxicillin in drug delivery systems intended to improve oral bioavailability of this drug.
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