The present work reports the study of different Lamivudine (LAM): excipient formulations, in order to determine the effect of the polymer substitution and type of diluents on the drug-release mechanism. Seven formulations were prepared using either HPMC K15M alone or in combination with Ethyl Cellulose (EC). Release kinetics was evaluated by using United States Pharmacopeia (USP)-22 type I dissolution apparatus. The tablets were tested for their drug content, weight variation, hardness, thickness, tensile strength, friability, swelling and release ratio. Polymers HPMC K15M was found not to be appropriate for the preparation of modified release LAM hydrophilic matrix tablets, while combination of HPMC K15M and EC showed to be advantageous. The analysis of the release profiles in the light of distinct kinetic models (zero-order, first-order, Higuchi and Korsmeyer–Peppas) led to the conclusion that the concentration of polymer did not influence the release mechanism of the drug. The mean dissolution time (MDT) and t50% was determined, the highest MDT and t50% value being obtained for HPMC and EC formulations. Moreover, the drug-release process was not found to be influenced by the type of diluents, either MCC or DCP. Key words: Lamivudine, HPMC, Ethyl Cellulose