Because drug-surfactant interactions are specific, careful choice of surfactant media is required to develop dissolution tests for Biopharmaceutics Classi.cation System (BCS) Class II drugs. The purpose of this study was to investigate the effects of cationic hexadecyltrimethylammonium bromide (CTAB) and nonionic surfactants (polysorbate 80) on the dissolution of bioequivalent immediate-release formulations of a BCS Class II anticancer drug, tamoxifen citrate (TMX), and to identify the most suitable surfactant medium reflecting the formulation differences and in vivo dissolution of the drug. Dissolution behaviors of the reference and test products were studied using USP apparatus II at pH 1.2, 4.5, and 6.8 with and without surfactant. At pH 6.8, the effects of 0.5% (w/v) CTAB and 0.5% (w/v) polysorbate 80 on dissolution of the formulations were much more pronounced compared to pH 1.2. Based on model-dependent and model-independent approaches, test products were found to be different from the reference in all surfactant media. Overall, none of the surfactant media reflected the bioequivalence of test products to the reference; however, polysorbate 80 may provide a discriminative test for certain formulation changes, and it may be physiologically meaningful to mimic in vivo solubilization and sink conditions due to continuous intestinal absorption of TMX.