Bioavailability of itraconazole in rats and rabbits after administration of tablets containing solid dispersion particles

A tablet dosage form containing solid dispersions of itraconazole (Asd tabl ets) was prepared by using the spray-drying and wet granulation methods. Th e dissolution rate of itraconazole from Asd tablets was fast, with more tha n 90% released within 10 min, compared to less than 20% for a marketed prod uct, Sporanox((R)) capsules. The oral absorption of itraconazole from Asd t ablets was determined in rats and rabbits and was compared with that for Sp oranox capsules. In the rat, there was no difference between the Asd tablet s and Sporanox capsules in the mean area under the curve (AUC) (3089.5 +/- 4332.8 ng . hr/ml and 3653.9 +/- 2348.9 ng . hr/ml, respectively) and C-max (295.0 +/- 344.5 and 390.5 +/- 169.4 ng/ml, respectively). Also, in the ra bbit, no difference was found between the two products in the mean AUC (AUM C; 19357.9 +/- 5117.5 ng . hr/ml and 23382.2 +/- 6236.5 ng . hr/ml, respect ively) and C-max (766.4 +/- 276.5 and 1127.5 +/- 577.9 ng/ml, respectively) . Despite the rapid in vitro release characteristics of itraconazole from t he Asd tablets, the in vivo absorption of itraconazole was comparable to th at of Sporanox capsules, with no difference in T-max in both animal species . Serum levels of the major active metabolite hydroxyitraconazole were also measured. Itraconazole was rapidly converted to hydroxyitraconazole in bot h rats and rabbits, but there were species-specific differences in their ph armacokinetics. It is concluded that, in addition to drug solubility and di ssolution characteristics, other formulation factors such as the physical s tate of the drug and the granulation process, may also need to be considere d in the prediction of the in vivo absorption of itraconazole based on in v itro data.