Abstract

DESIGN, OPTIMIZATION, AND IN VITRO BIOEQUIVALENCE EVALUATION OF A GLUCOCORTICOID-CONTAINING NASAL SPRAY FOR ALLERGIC RHINITIS: A QUALITY BY DESIGN-BASED DEVELOPMENT STRATEGY

Ünnügülsüm ErdoÄŸan*, Ceren Okuyucu GENÇ, Enis IÅžIK, Banu Özkirim Arslan,

Abstract

The aim of this study was to design, optimize, and evaluate the in vitro bioequivalence of a glucocorticoid-containing nasal spray for the treatment of allergic rhinitis, following a Quality by Design (QbD)-based development strategy. A systematic experimental design approach (Plackett–Burman design) was employed to identify critical formulation and process parameters influencing product quality. Beclomethasone dipropionate was selected as the active pharmaceutical ingredient, and benzalkonium chloride and phenyl ethyl alcohol was used as preservative. The optimized formulation was subjected to comprehensive characterization including physicochemical tests, rheological evaluation, and scale-up feasibility. In vitro bioequivalence was assessed in accordance with FDA guidelines, using spray pattern, plume geometry, droplet size distribution, aerodynamic particle size distribution, and single actuation content tests. The optimized formulation demonstrated consistent physicochemical properties, acceptable rheological behavior, and robustness under stability studies. In vitro equivalence with the reference product was confirmed for critical attributes, including spray performance and droplet size distribution, with population bioequivalence (PBE) criteria being met. The formulation showed favorable stability, preservative efficacy and reproducibility upon scale-up. A QbD-driven development strategy enabled the successful formulation of a bioequivalent beclomethasone dipropionate nasal spray. This approach demonstrates the effectiveness of QbD principles in ensuring product quality and regulatory compliance for locally acting nasal formulations.

Keywords: Beclomethasone Dipropionate, Quality by Design (QbD), Nasal Spray, In Vitro Bioequivalence, Optimization, Allergic rhinitis.