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Drug permeation through membranes. 3. Effect of pH and various substances on permeation of phenylbutazone through everted rat intestine and polydimethylsiloxane.

Abstract The permeation rate of phenylbutazone through membranes of polydimethylsiloxane and everted rat intestine was measured over a range of pH values. The classical pH-partition hypothesis was not obeyed. Permeability coefficients were calculated using a modification of Higuchi's general equation relating pH and permeation rate. The effect of various substances on the permeability coefficient was determined. Phenylbutazone permeation rates in one or both membranes decrease in the presence of gelatin, methylcellulose, polyvinylpyrrolidone, skim milk, albumin, sodium lauryl sulfate, polysorbate 80, and cetrimonium bromide. Permeation rates through everted intestine were enhanced by bile salt concentrations below the cmC and by porcine mucin, while rates through polydimethylsiloxane were unaffected. Substances having no apparent effect were: lactose, starch, talc, kaolin, calcium chloride, acacia, calcium sulfate, sucrose, sodium saccharin, cholesterol, ferrous sulfate, and magnesium stearate.