Abstract

Factors affecting reduction in the permeation rate of nitrofurantoin and hydrocortisone acetate from methylcellulose solutions through a cellulose membrane were investigated. The factors evaluated were the effect of polymer agglomeration and whether the drugs formed a complex with the polymer. The influence of polymer agglomeration was evaluated by dynamic dialysis studies of nitrofurantoin dissolved in solutions of methylcellulose 400 cps, which agglomerates, and in methylcellulose 50 cps, which does not exhibit this behavior. Dialysis rates of this drug were measured as a function of polymer concentration, ionic strength, heating time prior to measurement, and temperature. The effect of polymer agglomeration on the permeation rates of hydrocortisone acetate was studied by varying the ionic strength of the drug–polymer solution. Complex formation studies were conducted for both drugs by the equilibrium dialysis method. Polymer agglomeration caused a substantial reduction in the dialysis rate of both drugs in methylcellulose 400 cps solutions. There was less reduction in the dialysis rate of nitrofurantoin with increased polymer concentration of methylcellulose 50 cps solutions, which was attributed to the increase in the bulk viscosity of the solution. There was no evidence of complex formation of the drugs with the polymers.

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