This study outlines a framework for developing a texture analyzer-based mucoadhesion method integrated with rheology analysis for evaluating ointment formulations. Using an Analytical Quality by Design (AQbD) approach, key sources of variability affecting critical method variables (CMVs) were identified. A Box-Behnken design evaluated applied force, contact time, and trigger force, with optimal conditions selected via response surface methodology (RSM) within the method operable design region (MODR). The final conditions-2 N applied force, 60 s contact time, and 0.05 N trigger force-ensured compliance with the analytical target profile (ATP). Incorporating mucin dispersion revealed significant rheological synergism, validating the optimized method. The framework adheres to ICH guidelines, demonstrating robust and reproducible performance.