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The present investigation concerned with formulation design and evaluation of oral sustained release matrix tablets of Didanosine (DDI) prepared by direct compression method using various proportion of release retarding polymer viz; HPMC K15. The prepared tablets were evaluated for weight variation, percentage friability, hardness and in vitro dissolution studies and all the formulations showed compliance with pharmacopeia standards. In vitro release studies were performed using USP type II apparatus (Paddle type) at 50 rpm. Formulation F1 failed to sustain release beyond 10 hours and the cumulative percentage of drug release is not more than 85 % at the end of 12 hour in formulation F5. The formulations F2, F3 and F4 sustained release of drug for 12 hrs with 31.32%, 28.27 % and 23.34% release of drug after 1hr and more than 90 % at the end of 12 hrs. The release kinetics was analyzed using Zero-order model equation, Higuchi’s square root equation and Korsmeyer and Peppas ’ empirical equation. The regression coefficient obtained for first order kinetics were found to be higher (R 2: 0.985 to 0.991) when compared with those of the zero order kinetics (R 2: 0.311 to 0.897), indicating that drug release from all formulations followed first order kinetics. The mechanism of drug release from formulation F1 to F3 showed behavior of Fickian diffusion and remaining all formulations showed non-Fickian diffusion