Interpenetrating polymer network (IPN) microspheres of poly(vinyl alcohol) (PVA) and methylcellulose (MC) prepared by a water-in-oil emulsion method were crosslinked by glutaraldehyde and loaded with theophylline (THP), an antiasthmatic drug, with various ratios of PVA to MC. Microspheres were characterized with X-ray diffraction to determine the crystalline nature of the drug after encapsulation. Fourier transform infrared spectroscopy was used to assess the formation of the IPN structure and to confirm the absence of chemical interactions between the drug, polymer, and crosslinking agent. Differential scanning calorimetry confirmed the molecular-level distribution of THP in the polymer matrix, whereas scanning electron microscopy suggested the formation of clustered spherical particles. Zeta-sizer indicated that the particle sizes ranged from 4 to 57 pm, A THP encapsulation efficiency of up to 84% was achieved, as confirmed by ultraviolet spectrophotometry. Dynamic/equilibrium swelling experiments performed in pH 7.4 buffer media provided important information on drug diffusion characteristics. In vitro release studies performed in pH 1.2 and 7.4 buffer media indicated that the drug release depended on the extent of crosslinking as well as the amount of MC in the microspheres. Drug release was extended up to 3 h, and the results, as analyzed with an empirical equation, indicated non-Fickian transport for the release of THP. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 116:1226-1235,2010