IN-VITRO AND IN-VIVO EVALUATION IN DOGS AND PIGS OF A HYDROPHILIC MATRIX CONTAINING PROPYLTHIOURACIL

A hydrophilic matrix tablet containing 300 mg of propylthiouracil was formulated with several types of hydroxypropylmethylcellulose. The inf luence of polymer and drug granule particle size, polymer concentratio n, crystallinity and geometry of the polymer particles, the polymer in corporation outside or inside the granule, addition of a filler and ta blet hardness were studied. Polymer concentration, polymer particle si ze and geometry, filler addition and type of the filler used had a maj or influence on in vitro drug dissolution profiles. The bioavailabilit y of propylthiouracil in dogs from the hydrophilic matrices investigat ed was low, because of the short gastro-intestinal transit times of th e matrix tablets in the dogs. The matrix tablets reached the colon in fasted dogs within 2-3 hours after administration. The results indicat ed the poor predictability of bioavailability experiments in dogs with hydrophilic matrices. Although the bioavailability data in pigs seeme d promising, a transit time study revealed a long stomach residence ti me of the matrix tablets in pigs. These data suggested that pigs are a n inappropriate animal model for bioavailability studies of erodible m atrix tablets.