DIFFUSION CONTROLLED DRUG RELEASE THROUGH SYNTHETIC POLYMERIC MEMBRANES (POLYMETHYL VINYL ETHER)

An investigation was undertaken to determine the feasibility of utilizing a previously introduced controlled diffusion film coating to provide an improved delivery system for a model drug. Various combinations of poly (methyl vinyl ether/maleic anhydride) 169 copolymer (PVM/MA) cross-linked with Tween 20 and plasticized with triacetin were evaluated for potential use as controlled diffusion tablet coatings. Using tetracycline HCl as the model drug, the in vitro release rate and film coat rupture resistance were evaluated as functions of the tablet substrate composition, the concentrations of crosslinker and plasticizer in the film coat, and film thickness. The equilibrium linear swelling ratio, used as an index of the extent of the polymer-crosslinker reaction and the relative potential drug transport rate, was studied as a function of the elevated temperature-humidity pretreatment conditioning time, the crosslinker concentration and the plasticizer concentration. Criteria such as in vitro drug release rate, hydrated film rupture resistance, swelling properties, potential gastric residence time, and general physical properties affecting the stability and integrity of the film coat were applied in selecting the film and tablet formulation for final in vivo evaluation. The physical integrity of the dosage forms as well as in the in vitro release rate of tetracycline HCl from film coated tablets were found to be sensitive to formulation factors such as the type and amount of binder-diluent and lubricant used in the substrate tablets. As the Tween 20 crosslinker concentration was increased over the broad range of from 3.0% to 15.8% the apparent first order in vitro release rate of tetracycline HCl through applied films was found to pass through a maximum value near 6.5% (about 8:0.56 ratio) Tween 20. As the triacetin concentration, in similarly crosslinked PVM/MA applied films, was increased from 27.3% to 50%, the tetracycline release rate passed through a minimum value near 38.5% (8:5 ratio) plasticizer. Increased tack and drying times required between coats also increased with increasing triacetin concentration. No simple inverse relationship was found between film coat thickness and film permeability. Increased drug permeation rates at greater film thicknesses were hypothesized to result from solvent stress cracking. . . . (Author\u27s abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UM