Controlled-release systems of drug administration are discussed with an explanation of how the controlled release of agents according to zero-order of 1st-order kinetics (or other patterns) arises from membrane-moderated devices and the application of diffusion laws. Parameters which determine the release rate are discussed and it is shown how the release rate changes with alterations in these parameters. 2 types of membrane-moderated controlled-release devices are described: 1) those which are composed of a core of active agent surrounded by an inert diffusion barrier and 2) those in which the active agent is dissolved or dispersed in the diffusion barrier.

Controlled release: mechanisms and release.

Castration of mice in freerunning conditions (total darkness, DD) causes a reduction of running wheel activity in the beginning of the active period (alpha) and stimulates activity at the end of alpha. Simultaneously, the period (tau) of the freerunning rhythm is increased. Both effects are abolished by implantation of a Silastic capsule from which a physiological dose of testosterone is released at a constant rate. The results are tentatively explained by differential endocrine influences on two oscillating components in the pacemaker of the circadian activity rhythm.

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An effect of castration and testosterone replacement on a circadian pacemaker in mice (Mus musculus)

Oral administration and intraperitoneal implantation can be used to administer cortisol to the brown trout. Both techniques produce a dose-dependent increase in plasma cortisol concentration and the experimental procedures reduce the stress response in control fish to a minimum level. The plasma levels of the steroid are within the physiological range for the fish and the time of the response to acute oral administration is similar to that for such stresses as crowding, pollution and confinement. The evidence strongly indicates that elevated cortisol levels can significantly increase the susceptibility of salmonid fish to a wide range of infectious diseases including furunculosis and fungal infection. The present study has shown that this can occur at cortisol levels within the normal physiological range of the fish.

Administration of cortisol to brown trout, Salmo trutta L., and its effects on the susceptibility to Saprolegnia infection and furunculosis

Summary. Experiments were designed to examine the release of testosterone through polydimethylsiloxane (PDS) capsules in vitro and in situ and to test the efficacy of PDS capsules in maintaining testosterone in the peripheral circulation of castrate male rabbits for several months. The results demonstrate that (1) tritiated testosterone passed through PDS capsules suspended in water, (2) the tritiated material released into water had the same chromatographic mobility as authentic testosterone when subjected to thin-layer chromatography, (3) the rate of release of testosterone into water was dependent upon capsule surface area, (4) the release of testosterone from implants in situ was dependent upon surface area but independent of implantation site (i.e. subcutaneous versus intraperitoneal implants), and (5) the release of testosterone from PDS capsules in situ remained relatively constant over a span of 3 months. Castration abolished libido and caused accessory sex organ atrophy in male rabbits, but subcutaneous placement of testosterone-filled PDS implants (430 mm2, 0\m=.\245mm thick) maintained these androgendependent characteristics at normal levels. The concentrations of seminal fructose, citric acid and plasma testosterone noted in castrate rabbits receiving testosterone implants in situ were virtually identical to those noted in intact rabbits receiving similar implants containing cholesterol for 3 months.

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I. Angee

Papers

Sustained release hormonal preparations: I. Diffusion of various steroids through polymer membranes.