Studies on the Absorption of Subcutaneously Implanted Tablets of Hexoestrol

1. The large compressed tablets of pure hexoestrol used, possess a ‘labile’ component (that may or may not be located in the surface zone), which is quickly lost on subcutaneous implantation or incubation with blood plasma or water. The remaining surface is much less soluble. 2. Tablets implanted subcutaneously after having suffered loss of the ‘labile’ component, because of previous in vivo implantation or incubation with blood plasma or water, undergo less absorption in a given time than unused tablets. 3. In consequence of (1), absorption curves for 1000, 500 and 250 mg. tablets in the bovine, goat, rabbit, guinea-pig, rat and pigeon show two phases, an initial phase of rapid absorption due to the loss of the ‘labile’ component, after which the curves bend sharply and thereafter pursue a linear course (linear phase). On the other hand, curves for 50, 25 and 15 mg. tablets in the rat are linear and pass through or very near the origin. 4. During the implantation period, hexoestrol tablets (and also tablets of steroid hormones) become infiltrated with structures (ghosts) composed of insoluble protein, probably a scleroprotein, formed by reaction between the hormone and soluble protein present in the tissue fluids. Ghosts are quite distinct from the fibrous-connective tissue capsules which are often formed round tablets in vivo. 5. Ghosts are also formed in hexoestrol tablets immersed in blood serum or plasma and protein solutions. 6 . Absorption values (apparent), determined by losses in weight during implantation, are in each case lower than the true value by the weight of the ghost and, on extrapolation, true absorption curves make larger intercepts on the vertical axis than apparent curves. 7. In consequence of (6) the curves for small tablets in rats are in reality of the same form as those for larger tablets, though here the difference made by the ghost correction is small. Such curves, when corrected for ghost formation, thus make only small intercepts on the vertical axis indicating that the ‘labile’ component is much less important in the small tablets than in the 250, 500 and 1000 mg. classes. 8. The absorption rate during the linear phase is the characteristic absorption rate for any given weight class of tablet. Absorption rates per mm. 2 for tablets of various sizes in different animals are approximately constant, provided the tablets are not too big in relation to the size of the animal, showing that absorption rate is proportional to surface