A comparison of the dissolution and bioavailability characteristics of three spironolactone tablet formulations, including preliminary data on two spironolactone metabolites.
The bioavailabilities of three spironolactone tablet formulations specially selected for major differences in in vitro dissolution tests were compared in normal male volunteers by measuring plasma and urinary levels of the pharmacologically active spironolactone metabolite canrenone. It was possible to demonstrate small but statistically significant differences in plasma canrenone concentration-time curves derived from the three formulations together with significant differences in the time course of urinary canrenone excretion. The bioavailabilities of the three formulations did not differ significantly although the tablet with the poorest in vitro dissolution produced a significant delayed peak canrenone concentration. The dissolution rate methodology and results are described and an approach to the development of improved in vitro dissolution tests for spironolactone is suggested. The use of a new method for canrenone estimation resulted in the incidental detection of two other quantitatively significant spironolactone metabolites and preliminary information is given on these.
D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D002192:Canrenone / Q000097:blood / Q000652:urine; D002626:Chemistry, Pharmaceutical; D006801:Humans; D008297:Male; D008722:Methods; D012995:Solubility; D013148:Spironolactone / Q000008:administration & dosage / Q000378:metabolism*; D013607:Tablets; D013997:Time Factors
D013607:Tablets; D013148:Spironolactone; D002192:Canrenone