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Purpose: To prepare oral sustained release matrix tablets of a highly water soluble drug, tramadol hydrochloride, and to evaluate the effect of concentration of the hydrophobic polymer content and method of preparation on drug release. Methods: The tablets were a mixture of both tramadol hydrochloride and glyceryl palmitostearate (GP) prepared by melt granulation (MG1, MG2, MG3 and MG4 in ratios 1:1, 1:2, 1:3 and 1:4, respectively) or by direct compression (DC, 1:2 ratio). The hardness of the tablets was measured. Drug/GP interaction was determined by FT-IR spectroscopy while drug release from the matrix tablets was studied using USP II dissolution apparatus. The release data were subjected to different models in order to evaluate their release kinetics and mechanisms. Results: The hardness of the tablets was in the range of 5.30 ± 0.36 - 6.50 ± 0.10 kg/cm2. FT-IR spectra showed that there was no clear interaction between the drug and the glyceride. Of the formulations (MG1 to MG4) prepared by melt granulation, MG4 showed the most suitable sustained release, 58.4 ± 1.1 % in 12 h (p Keywords: Tramadol hydrochloride; Glyceryl palmitostearate; Melt granulation; Direct compression; Sustained release.

Preparation and Evaluation of Sustained Release Matrix Tablets of Tramadol Hydrochloride Using Glyceryl Palmitostearate