<p>Neurodermatitis and chronic eczema are characterized by severe itching and can lead to complications such as skin infections and folliculitis. Current treatment primarily involves glucocorticoid analogs which may be associated with side effects and lack of effective delivery strategies. The suspended ointment developed in this study aims to address these issues, offering improved therapeutic outcomes. The present study aimed to investigate the relationship between formulation/process variables versus the content uniformity and viscosity of neomycin sulfate and triamcinolone acetonide ointments and to explore the feasibility of using an in vitro approach to assess product sameness. Monofactor analysis was used to evaluate the impact of formulation and process variables. The new formulation was evaluated in terms of the prescription process, quality, stability, in vitro drug release behavior, and distribution of skin. The optimal prescription composition was 0.54% neomycin sulfate, 0.10% triamcinolone acetonide, 5.08% substrate A and 94.28% liquid paraffin. Quality and stability assessments confirmed that the formulation met the required standards for appearance and composition. Mathematical modeling of the drug release profile indicated that the release kinetics evaluated using the vertical diffusion cell method, closely aligned with first-order kinetics. Raman spectroscopy confirmed the successful penetration of triamcinolone acetonide into the skin, triamcinolone acetonide works primarily in the skin. Furthermore, skin irritation tests demonstrated that the formulation caused no detectable irritation. These results demonstrate that it can be a promising drug in treating neurodermatitis and chronic eczema.</p> Graphic Abstract <p></p>