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The isothermal kinetics of in vitro nicotinamide release from poly(acrylic-co-methacrylic acid) loaded xerogel into water was evaluated. The isothermal kinetics curves of nicotinamide release from poly(acrylic-co-methacrylic acid) xerogel were measured at different temperatures ranging from 296 K to 315 K. It was proven that the kinetics of nicotinamide release from poly(acrylic-co-methacrylic acid) xerogel was a kinetically complex process which was neither controlled by the processes of drug diffusion nor with the relaxation of the xerogel. The kinetic of nicotinamide release from poly(acrylic-co-methacrylic acid) may be described by the kinetics model of reversible first order chemical reaction and the apparent activation energy have value of Ea,M = 14.1 kJ mol−1 and preexponential factor ln(AM min−1) = 2.3. The rate constants of nicotinamide release ( inline image) and the rate constants of its reversible absorption reaction ( inline image) were calculated and found to fall within the range 0.019 min−1−0.033 min−1 for inline image and 0.014 min−1−0.016 min−1 for inline image. The value of activation energy for the nicotinamide releas, Ea.R =21.25 kJ mol−1, is significantly higher than the value for the process of nicotinamide absorption (Ea,A = 2.6 kJ mol−1). The rate of nicotinamide release was predetermined with the rate of nicotinamide molecules distribution between the hydrogel and surrounding solution. POLYM. ENG. SCI., 55:60–69, 2015. © 2014 Society of Plastics Engineers