Permeation of lipophilic drugs through synthetic elastomers

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)