Correlation was demonstrated between dissolution and several measures of bioavailability for powder and tablets of isonicotinic acid hydrazide (INH). Aqueous solution, powder, six tablets produced by Japanese manufacturers (A, B, C, D, E, F), and two tablets prepared in the laboratory (G-I, G-II) were examined. Dissolution rate curves, measured by the beaker method (pH 1.0, 75 rpm), were linearized by the Weibull plot and first-order plot applications. Dissolution efficiency was also calculated. In these samples, commercial tablets (A-F) and powder dissolved rapidly. Bioavailability was compared in seven formulations (solution, powder, A, B, C, G-I, G-II) by measuring amount of urinary excretion of INH in four healthy male subjects in cross-over study, by oral administration of 100 mg of each formulation after an overnight fasting. No significant differences were noted among aqueous solution, powder, A, B, C, and G-I in maximum excretion rate or in cumulative amount excreted during 24 hr. The maximum excretion rate time decreased in the order of solution, powder, A, B, C, G-I, and G-II. In vivo dissolution rate in the digestive tract, calculated by the de-convolution method, also showed the same tendency. The correlation between dissolution rate and bioavailability was examined quatitatively. The formulations, of which t
50 values were less than 20 min or DE values were more than 50%, showed no difference in their bioavailability. However, the formulations that dissolved more slowly showed poor bioavailability. These results support the use of dissolution test to predict the bioavailability of INH.
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