The Effect of Four Tablet Binders on the Bioavailability of Frusemide from 40MG Tablets

Abstract

Tablets containing frusemide 40mg have been prepared using four different binders; polyvinylpyrrolidone, starch mucilage, stearic acid and methylhydroxyethyl cellulose. With the exception of the tablets prepared using stearic acid, all the tablets disintegrated in under 2 minutes and exhibited hardnesses ranging from 12 to 17 s.c.u. The dissolution rate, measured in the B.P. apparatus as the time to achieve 50% solution in distilled water, discriminated more effectively between the tablet batches. Tablets made using polyvinylpyrrolidone and methylhydroxyethyl cellulose had dissolution half lives of 3.65 and 3.30 minutes respectively, whilst tablets incorporating stearic acid and starch mucilage exhibited respective values of greater than 200 minutes and 117 minutes. The bioavailabilities of the four tablet formulations were assessed on a double blind basis in four healthy males aged 18-30 with reference to an oral frusemide solution. The bioavailability of each formulation was determined by two different methods and it was found that polyvinylpyrrolidone and methylhydroxyethyl cellulose rendered frusemide equally bioavailable (71.7% and 71.6% respectively) whilst the starch mucilage formulation rendered frusemide 25% less bioavailable (54.10%). The poorest binding agent was stearic acid which decreased the bioavailability of frusemide by 50% (35.04%). The results indicate that the choice of binding agent can significantly affect the bioavailability of frusemide from tablets and that these bioavailability differences can best be detected in vitro by dissolution rate measurements.