Drug release and its relationship with kinetic and thermodynamic parameters of drug sorption onto wheat gluten (WG) fibers have been studied using Diclofenac, 5-Fluorouracil (5-Fu), and Metformin as model drugs. Both sorption and dissolution methods were used to examine the drug release rates in phosphate buffered saline (PBS pH 7.4) and artificial gastric juice (AGJ pH 1.2). To understand drug release of WG fibers using the sorption loading method, kinetic, and apparent thermodynamic parameters, such as diffusion coefficient, activation energy for diffusion, affinity, and sorption enthalpy and entropy, have been investigated. It has been found that the sorption method at high temperatures has a lower initial burst and more constant release than the dissolution method for Diclofenac on WG fibers. Quantitative relationship between drug release and drug loading concentration, affinity, and activation energy for diffusion was established to predict initial bursts and later release of the drugs. The study showed that the Diclofenac had high initial bursts in PBS but more constant release in AGJ because the ionic force between the drug and WG fibers was readily broken in a high pH solution. It also has been found that drugs with higher activation energy for diffusion, lower diffusion coefficients, and higher affinity (especially van der Waals force) on WG fiber, are more suitable for sorption loading at elevated temperatures to achieve higher loading capacity and more constant releasing rate. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 116: 708-717, 2010