Dependence of area under the curve on proquazone particle size and in vitro dissolution rate.

ABSTRACT

The in vitro dissolution and GI absorption of various sieve fractions of proquazone were studied (particle-size ranges of 45-74, 160-300, and 500-1000 micrometer). The dissolution rates of preparations F45, F160, and F500 were determined in vitro in a flow-through assembly in artificial gastric juice at 37 degrees. The time required for 63% of the maximum amount of soluble drug to pass into solution was characterized by the dissolution variable tau D. The in vitro dissolution rates for the preparations differed significantly in the order tau D, F45 less than tau D, F160 less than tau D, F500. After oral administration of 300 mg of the fractions to each of eight rhesus monkeys, the area under the plasma level-time curve (AUC) differed significantly in the order AUC F45 greater than AUC F160 greater than AUC F500. The dissolution rate increased with decreasing particle size. The AUC increased with decreasing particle size and with increasing dissolution rate. These results indicate that the dissolution rate probably determines the extent of absorption when dissolution is rate limiting.