The purpose of this work was to formulate prolonged release matrix tablets with water soluble opioid drug (API) using different types of hydroxypropylmethyl cellulose (Methocel) as controlled release polymers. Methocel K100M was incorporated as intra-granular polymer (sample 1) along with Methocel K4M (sample 2) or Methocel K15M (sample 3) as extra-granular polymers. The final blends and tablets prepared by wet granulation process were fully characterized. Results showed that the polymer used extra-granularly significantly affects the tablet properties. By incorporation of Methocel extra granularly (samples 2 and 3), the hardness and tensile strength of the tablets increased and the total tablet porosity decreased. Sample 1, containing only Methocel K100M (intra granularly) has the lowest index of swelling and the fastest release of API probably due to the cross-linking of the polymer chains during the process of wet granulation. Also, the type of Methocel used extra-granularly (with different viscosity grade) was found to significantly affect the swelling ratio of the designed matrix systems and the drug release behavior. Sample 2 containing Methocel K4M extra-granularly has a lower index of swelling and faster release of API compared to sample 3. Considering the release mechanism, release data showed best fitting to the heuristic model proposed by Korsmeyer-Peppas. Two additional approaches were used for mathematical modeling of the release data in order to make them directly applicable for our experimental results. Keywords: matrix tablet, water soluble opioid drug, prolonged release, HPMC (Methocel)