A hydrophilic matrix-based, controlled-release formulation for venlafaxine HCl (Ven HCl) was developed using a combination of various forms of hydroxypropyl methylcellulose (HPMC K4M, K15M, and K100M). The aim of the development was to match the dissolution profile (similarity factor f 2 > 50) of Effexor XR capsules. The dissolution profile studies for the optimized formulation were performed as per the FDA guidelines for modified-release (MR) products using a QbD approach. The data show that the matrix-based formulation is statistically similar to Effexor XR in multimedia dissolution testing at different rpm, and the results between USP Apparatus 1 and 2 are similar. An alcoholinduced dose-dumping study was also performed, and the results are comparable. This indicates that the hydrophilic matrix tablet formulation is equivalent to Effexor XR, which is based on a coated-pellet platform.