Comparison of thein vitro andin vivo release of digoxin from four different soft gelatin capsule formulations

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Abstract
A blinded, four-treatment crossover study in 16 normal adult male volunteers compared plasma concentrations and urinary excretion of digoxin, measured by radioimmunoassay, after oral administration of soft gelatin capsule formulations of digoxin. Four 0.4-mg formulations with different in vitro“burst times” and dissolution rates were administered, with 2- week intervals between treatments. The two capsules with lowest in vitroburst times (2.9 and 16 min) gave comparable in vivoresults. The other two capsules, with in vitroburst times of 62 and 229 min, produced significant delays in digoxin absorption. In vitro-in vivocorrelations were obtained by comparing the logarithm of the in vitro burst time with time to peak plasma level and the time to the first measurable plasma level (≥ 0.05 ng/ml). Also, the mean time to peak plasma level correlated with the logarithm of the time required to release either 50% or 85% of the digoxin in vitro. No significant changes were found in the amount of digoxin absorbed from each capsule as determined by urinary excretion or AUC0-∞.