An interpenetrated polymer network (IPN) poly(NIPAAm-co-AAc) hydrogel was synthesized by two polymerization method: emulsion and solution polymerization. The pH- and temperature-sensitive hydrogel was loaded by swelling with riboflavin drug, a B2 vitamin.The release of riboflavin as a function of time has been achieved under different pH and temperature environments. The determination of experimental conditions and the analysis of drug delivery results were achieved using response surface methodology (RSM). In this work, artificial neural networks (ANNs) in MATLAB were also used to model the release data. The predictions from the ANN model, which associated input variables, produced results showing good agreement with experimental data compared to the RSM results. (C) 2017 Elsevier B.V. All rights reserved.