Trimetazidine dihydrochloride is absorbed quickly from immediate release dosage form and attains very low con-centration in plasma at time of next dose. To maintain constant drug plasma level, matrix tablets were prepared with varying Methocel E concentrations and their in vitro drug release was studied. Effects of hydrophobic and hydrophilic binders, lubricant concentration and effect of water insoluble diluents on in vitro drug release were studied. Effect of Methocel E was compared with the effect of Methocel K. The formulated products were also compared with marketed product. Low viscosity Methocel formulated matrix tablets F1 to F3 showed fast release of drug. F6 was best formulation which released drug for 12 h while high viscosity Methocel in F7 to F9 showed very slow drug release which extended for more than 12 h. Hydrophobic binders in F10 to F13 showed slow release of drug. Low concentration of PVP K25 showed fast release of drug. Water insoluble diluent DCP reduces release rate of drugs while there was no change in drug release rate after changing contents of lubricants in formulation. Mathematical treatment of the in vitro drug release suggests that formulations best fitted in first order release kinetics. Drug release from the matrix occurred by combination of two mechanisms, diffusion of drug from tablet matrix and erosion of tablet surface which was reflected from Higuchi’s model