In this study, we evaluated the correlation between the response surfaces for the tablet characteristics of placebo and active pharmaceutical ingredient (API)-containing tablets. The quantities of lactose, cornstarch, and microcrystalline cellulose were chosen as the formulation factors. Ten tablet formulations were prepared. The tensile strength (TS) and disintegration time (DT) of tablets were measured as tablet characteristics. The response surfaces for TS and DT were estimated using a nonlinear response surface method incorporating multivariate spline interpolation, and were then compared with those of placebo tablets. A correlation was clearly observed for TS and DT of all APIs, although the value of the response surfaces for TS and DT was highly dependent on the type of API used. Based on this knowledge, the response surfaces for TS and DT of API-containing tablets were predicted from only two and four formulations using regression expression and placebo tablet data, respectively. The results from the evaluation of prediction accuracy showed that this method accurately predicted TS and DT, suggesting that it could construct a reliable response surface for TS and DT with a small number of samples. This technique assists in the effective estimation of the relationships between design variables and pharmaceutical responses during pharmaceutical development.