Optimization of Polymer‐Based Gel Formulations Using Cross‐Model Rheology and Design of Experiments

The rheological properties of polymer‐based gel formulations were investigated to optimize their flow behavior for pharmaceutical applications. Eleven gel formulations were prepared with two gelling agents: Carbopol 934 and hydroxyethylcellulose. These were characterized over a wide range of shear rates. The rheological data revealed marked shear‐thinning behavior for all formulations and were accurately described by the cross‐model ( R 2 = 0.9999). While the Carbopol–HEC combination has been previously reported, this study provides a systematic and quantitative evaluation of the individual and combined effects of these polymers on zero‐ and infinite‐shear viscosities. Beyond conventional rheological characterization, the cross‐model parameters were quantitatively exploited as functional responses within a design of experiments methodology (DoE). This enabled the rational optimization of gel composition. In particular, zero‐shear viscosity ( η 0 ) and infinite‐shear viscosity ( η ∞ ) were identified as key descriptors governing both structural stability at rest and ease of application. The combined rheological and statistical approach provides a predictive tool for tailoring gel formulations with controlled flow properties. This strategy can be applied to the design of optimized semisolid systems. The chosen model was validated, exhibiting high coefficients of determination ( R 2 between 0.9 and 0.98). The optimal formulation, which meets the target performance criteria, contains 2.74% Carbopol 934 and 0.40% HEC.