Using vitamin C as a model drug we focus our attention to the experimental and theoretical investigation of swelling equilibria of ternary system made from water, cross-linked poly (N-isopropylacrylamide) and vitamin C. This contribution aims to the prediction of the amount of drug uptake by the hydrogel using a thermodynamic model and independent experimental information, like the demixing behavior of linear polymer in water and in aqueous vitamin C solutions as well as the solubility of vitamin C in water. As theoretical approach a combination of the Koningsveld-Kleintjens model for the Gibbs energy of mixing and the affine network theory for the elasticity of the gel is applied. The model shows an excellent performance in the prediction of the degree of swelling as function of vitamin C concentration and in the amount of drug in the hydrogel. Only for the calculation of the temperature dependency two parameters must be refitted slightly in order to achieve quantitative agreement with the experimental data. From the experimental point of view some hysteresis effects, growing with increasing vitamin C concentration are found, especially in the transformation range. (C) 2010 Elsevier B.V. All rights reserved.