The influence of polyvinylpyrrolidone on the solution and bioavailability of hydrochlorothiazide

The dissolution properties of hydrochlorothiazide-PVP 10 000 mechanical mix and coprecipitate systems were qualitatively similar to those previously reported using hydroflumethiazide. Quantitative differences were dependent on the proportion of PVP present, its molecular weight and method of incorporation. Cumulative urinary excretion data from test capsule preparations showed that bioavailability was enhanced by the presence of PVP. However, the degree of enhancement was less than that expected from constant surface area disc rate studies. Dissolution tests on the capsule formulations, using the U.S.P. basket stirrer assembly, did not correlate with in vivo results. Using the Levy beaker method and a stirring speed of 40 rev min-1, good correlation between amount dissolved in 30 min and amount excreted in urine after 24 h was obtained. The dissolution tests revealed that PVP retards the initial dissolution from capsule dosage forms, probably by retarding deaggregation and dispersion of drug particles.