Permeability studies were carried out with three lipophilic drugs, namely,
phenytoin and
primidone (both widely used in the treatment of
epilepsies and convulsive disorders), and
dapsone (a
sulfone antimicrobial agent used in the treatment of
leprosy and to a lesser extent in
dermatitis herpetiformis) through
silica-filled poly(dimethyl
siloxane) (
Silastic) membranes, and anisotropic membranes of poly(
ether-
urethane)/poly(dimethyl
siloxane) block copolymer (
Avcothane,
Cardiothane). These
polymers are used in medical implants and in various cardiovascular devices. While both
polymers were permeable to the drugs, the transport properties differed significantly. In the case of the poly(dimethyl
siloxane) there was an initial large burst effect, followed by an exponential decrease in the rate of drugs released through the
polymer films, although with
dapsone the release rate became essentially constant between 100-180 h at 37 degrees C. In the case of the anisotropic films of the poly(
ether-
urethane)/poly(dimethyl
siloxane) block copolymer, the permeabilities were much higher. Significantly,
phenytoin exhibited essentially constant rate (zero-order) kinetics between 25-150 h, showing only a moderate burst effect that is probably not significant therapeutically. Importantly,
dapsone showed neither a burst effect nor any significant time lag, and the release followed constant rate (zero-order) kinetics between 12-80 h, followed by only a moderate decrease in
drug concentration up to 140 h (the experimental end-point). The diffusion coefficients calculated from initial desorption data at 37 degrees C for the poly(
ether-
urethane)/poly(dimethyl
siloxane) block copolymer are as follows:
phenytoin = 8.6 X 10(-9) cm2/s,
primidone = 2.8 X 10(-9) cm2/s, and
dapsone = 2.4 X 10(-8) cm2/s.(ABSTRACT TRUNCATED AT 250 WORDS)