In Vitro Equivalence Assessment Method for Atomization Characteristics of Budesonide Nasal Spray Products

In vitro testing is increasingly replacing systemic pharmacokinetic studies in assessing the equivalence of generic and reference locally acting nasal sprays. Establishing reliable in vitro methods and investigating factors that may affect equivalence tests is crucial. In this study, we evaluated the in vitro atomization characteristics of a self-prepared budesonide nasal spray (Formulation A) and a reference drug (Formulation B). A simple and efficient Python program was used to assess population bioequivalence, achieving a high level of automation with audit trail capabilities. The single actuation content, droplet size distribution, and plume geometry met the criteria for population bioequivalence (Hη <0). As the actuation force increased, droplet size decreased, with D90 (the diameter at a cumulative volume of 90%, the same below) exhibiting greater sensitivity to changes than D10 and D50. The spray patterns of the two formulations differed significantly, with Formulation B exhibiting a significant larger spray area than Formulation A. Stroke velocity was the factor with the largest influence on the spray pattern. For both formulations, drug particles <8.6 μm were below the HPLC detection limit (1.016 ng), confirming the safety of the formulation. The results indicate that device and drug interactions significantly influence nasal spray quality assessments, providing guidance for future formulation development and quality evaluation.