New formulation for treatment a copper deficiency in human organism was developed and optimized by application of mathematical modeling. This formulation contained copper (II) complex with polysaccharide pullulan, as active substance. The binder concentration [polyvinyl pyrrolidone (PVP %)], the disintegrant concentration (corn starch %) and the resistance to crushing (hardness) were taken as independent variables. In vitro measured drug release characteristics of the tablets at pH 1.20 and 7.56 were studied as response variables. Initially, the created full factorial 2(3) model showed that the resistance to crushing has the most significant effect on copper (II) complex release from the formulation. Optimal tablet formulation F2, with lower Hardness (50 N), lower Starch (20.0%) and higher PVP (2.7%) concentrations, is selected using the partial least squares (PLS) regression modeling. The selected formulation F2 has expressed the best drug release profile at both pH (98.66% pH = 1.20; 93.35% pH = 7.56), and the lowest variation of tablets weight. The presented theoretical approach and created PLS model can be readily applied in future copper complexes studies and formulation design.