PERMEABILITY OF BINARY POLYMER FILMS AS A CONTROLLED RELEASE MECHANISM

An investigation was undertaken to study the feasibility of employing a binary polymeric film, consisting of a highly water-soluble and an essentially water-insoluble component, as a controlled release pharmaceutical film coating. Upon exposure to alimentary fluids, the water-soluble polymer of the binary film was intended either to produce swelling of the coating or to be preferentially leached out from the coating leaving a porous but intact film network composed mainly of the insoluble polymer, through which diffusion and release of drug would take place. A completely water-soluble copolymer, poly(methyl vinyl ether/maleic anhydride) of PVM/MA was found to be compatible over a wide range of proportions with the water-insoluble methyl or ethyl methacrylates. Transparent, clear stable binary films were obtained by dissolving the PVM/MA and methacrylates in a common solvent, ethyl acetate, and casting free films on glass plates. The permeability of the free binary films of various grades of PVM/MA and methacrylates was measured in a diffusion cell maintained at 37(DEGREES), using amaranth in buffer solutions as the diffusing solute. The films were found to swell insignificantly in simuated gastric fluid and little diffusion occured. In the simulated intestinal fluid, which has a pH (7.50) well above the pK(,1) of the PVM/MA carboxylic groups, the binary films swelled due to the electrostatic repulsion of the negative charges on the dissociated PVM/MA carboxylic acid groups. The diffusion profile of amaranth across the binary films exhibited three distinct portions: a lag time, a zero order permeation rate period and an exponential rate period. During the lag time, water molecules started to penetrate the binary film hydrolyzing the PVM/MA anhydride to diacid and the film began to swell. As the swelling reached its equilibrium state, film permeability became and maintained constant throughout the entire zero order permeation rate period, after which the PVM/MA molecules began to leach out from the swollen binary film and the permeation rate increased exponentially with time. The permeation lag time of the binary films was observed to be directly proportional to the dry film thickness while the zero order and exponential permeation rates were inversely related to thickness. . . . (Author\u27s abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UM