The primary goal of this work was to develop a reliable in vitro dissolution model to evaluate the effects of Schiff-base hydrolysis and gel formation on the dissolution kinetics of pellets of porcine somatotropin (pST) and pST conjugated with ortho-vanillin (ov-pST) via Schiff-base formation, in an effort to develop an extended-release pST implant. Experimentally, dissolution was investigated as a function of ov concentration in pH 7.4, phosphate buffered saline under sink conditions where steady-state (constant flux) dissolution is typically observed. However, the resulting dissolution profiles displayed variable release rates due to gel formation at the solid-liquid interface, which impeded pST release. Chemical modification of pST with ov reduced gel formation and also resulted in much lower release rates. A mathematical model was developed that quantitatively accounts for changes in dissolution rates due to transient gel formation via irreversible aggregation, along with the effects of reversible Schiff-base hydrolysis involving ov, and predicts dissolution rates in the presence of ov decrease due to the much lower solubility of ov-pST. Our results indicate that although ov-pST is less prone to aggregate, pST/ov-pST equilibration is rapid compared to dissolution and therefore aggregation remains the limiting factor, and ultimately precludes this approach as a viable extended-release delivery system.