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SynopsisInterpenetrating polymer network (IPN) membranes and gradient-IPN polymers were synthesized by immersing crosslinked, 2-hydroxyethylmethacrylate copolymer beads which were swollen in polyol in solutions of diisocyanates. Diffusion of reactants and polycondensation take place simultaneously, and the polymer beads are modified by a polyurethane-IPN layer whose thickness and compositional gradient are a function of reaction rate and diffusion rate. When the reaction is fast relative to diffusion, the reaction zone is narrow and the IPN boundary layer is sharp, whereas when diffusion dominates, the reaction zone and the IPN-modified region becomes broader and more diffuse. A water-soluble drug imbibed into such gradient-IPN-modified hydrogel beads is released over a prolonged time period due to the less permeable IPN barrier and because of a drug-distribution gradient in the polymer, which follows the polyurethane gradient. Diffusion polycondensation can be considered a special case of interfacial polycondensation, one in which the interface area is expanded into and stabilized by a preformed polymer matrix, which serves as reaction medium.

Interfacial precipitation of silver halides in water-swollen polymer films occurred in complex, multilayered patterns if the concentrations of counterdiffusing reactants were unequal or decreased at different rates. Development of the rapidly forming Liesegang rings, which extend the phenomenon of periodic precipitation to the submicrometer range, is attributable to the combined effect of a moving reaction zone and periodic immobilization of colloidal silver halide.

Highly water soluble drugs, as they are typical for oral administration, can be released from polymer beads with low ( < 10%) water-but high ethanolswelling capacity at controlled rates, for up to 8 hours. The release of oxprenolol-HCl ( 77% water solubility) and diclofenac Na (2. 6% water solubility) from drug loaded monoliths is a function of water content and crosslink density. By partial extraction of the drug loaded beads the release can be further slowed down and, in the case of oxprenolol-HCl, delayed for several hours; the delay is dependent on water content of the polymer and is the result of the formation of a hydrophobic surface membrane.Hydrogel beads have first been proposed by 0. Wichterle (1) as drug carriers in oral drug delivery. They make an attractive multiparticulate oral dosage form because they can easily be synthesized, have good biocompatibility and provide very reproducible, diffusioncontrolled release.However, the release of large doses of highly water soluble drugs -conditions characteristic for oral deliveryfrom typical hydrogels such as poly-2-hydroxyethyl methacrylate is generally too fast and therefore limits the usefulness of such hydrogel beads to drugs with low water solubility or small dosages. To a certain extent the release can be slowed down by increasing the bead size; a doubling of bead diameter increases the half life for release about threefold. But even beads with diameters as large as 1.0-1.5 mm, which is the upper practical size limit for suspension polymerization, are not large enough to give practical release rates for very water soluble drugs.Previous attempts to reduce release rates include the synthesis of membrane covered and of gradient-beads by diffusion controlled interfacial polycondensation and grafting (2). Here the membranes delay the release by slowing down initial water absorption, whereas the compositional gradients result in a corresponding drug distribution gradient after drug loading and therefore give periods of almost constant release, although at the expense of total drug-loading.

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