A series of poly(acrylic acid)/poly(methyl vinyl ketone) (PAA/PMVK) blends with different compositions were prepared by the solvent casting method. The miscibility of this pair of polymers was investigated by differential scanning calorimetry(DSC), Fourier transform infra-red (FTIR) and X-Ray diffraction (XRD) techniques. An in-vitro cytotoxicity test of the drug-carrier system via MTT (3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay revealed no significant cytotoxic effects at concentrations up to 100 µg· ml−1. The STX/PAA-50 drug carrier systems were also prepared by solvent casting of solutions containing the sulfamethoxazole (STX) used as drug model and PAA/PMVK blend in N.N-dimethylformamide then crosslinked with acidified ethylene glycol. The release dynamic of STX from the prepared hydrogels was investigated in which the diffusion through the polymer matrix, the enhancement of the water solubility of STX, the influence of the initial drug concentration, the pH of the medium, and the effect of the degree of swelling of the polymer matrix on the release dynamic was evaluated. According to the total gastrointestinal transit time estimated by Belzer, the estimate distribution of STX released in the different organs indicated that the performance is obtained with the drug – carrier-system containing equal ratios of polymer and 10 wt% of STX (STX-10/PAA-50).