Minimization of initial burst in poly(vinyl alcohol) hydrogels by surface extraction and surface-preferential crosslinking

Surface extraction and surface-preferential crosslinking were investigated as effective methods to reduce the burst effect for proxyphylline release from poly(vinyl alcohol) hydrogels. Both these techniques involved changing the surface characteristics to reduce drug diffusion during the early stages of release, with the goal of subtracting the burst effect from the release profile without altering the long-term release rate. The extraction process was carried out on both relaxed and dry gels. Proxyphylline was extracted from both freshly made and dried hydrogel samples, with the extraction from dried samples providing better control of the burst effect with smaller amounts of drug removed from the gels. The success of extracting from the dried samples was attributed to the lack of drug diffusivity and redistribution after extraction when the majority of the device remained dry. Surface-preferential crosslinking, by dipping preformed proxyphylline-loaded samples in a concentrated crosslinking solution, effectively diminished the burst effect by slowing macromolecular relaxation near the surface. Notably, this technique maintained the same long-term drug release rate as the untreated gels and less than 0.2% of the loaded proxyphylline was removed during the crosslinking step. (C) 2002 Elsevier Science B.V. All rights reserved.