The objective of this study was to investigate the implications of changing dissolution parameters, including pH ramp time, absence and presence of simulated intestinal fluid (SIF), and the addition of a partitioning phase, using an automated dissolution-testing platform. The molar absorption coefficients, pKa, and dissolution characteristics of dipyridamole and piroxicam were investigated in the UV/Vis spectrophotometric and potentiometric platform, inForm (Pion Inc). Dissolution of dipyridamole and piroxicam from 10-mg compacts (tablets) was studied at pH 2.0 and 6.5 in fasted-state SIF version 2 (v2) and in biphasic media using decanol as the partitioning phase. Transfer through the gastrointestinal tract was simulated by shifting pH from 2.0 to 6.5 during dissolution testing. Dipyridamole (pK_a 6.0) dissolved rapidly at pH 2.0; however, changing the pH to 6.5 brought dipyridamole into a supersaturated state, from which it precipitated. Precipitation was slower in the presence of SIF, and higher dipyridamole concentrations were maintained in solution compared with simple buffer systems. In the biphasic dissolution assay, rapid distribution of dipyridamole into the lipophilic partitioning phase minimized drug precipitation. For piroxicam (pK_a1 1.9; pK_a2 5.3), the dissolution rate increased with increasing pH. The inclusion of SIF and introduction of a partition phase had limited influence on piroxicam dissolution. The automated platform facilitated efficient exploration of dissolution conditions. Tailoring of dissolution assays including pH gradients, SIF, and biphasic partitioning enabled detailed drug characterization, increased biorelevance, and possibly in vivo predictability. The use of a biphasic dissolution assay had a large impact on the in vitro dissolution of dipyridamole. The incorporation of an absorptive sink might be key for unraveling the supersaturation and dissolution behavior of weakly basic drug compounds.