Quality by design approach for development of suspension nasal spray products: a case study on budesonide nasal suspension.

The objective of this study was to provide quality by design (QbD) approach for development of suspension type nasal spray products. Quality target product profile (QTPP) of test product budesonide nasal suspension (B-NS) was defined and critical quality attributes (CQAs) were identified. Critical formulation, process and delivery device variables were recognized. Risk assessment was performed by using failure mode and effect analysis (FMEA) methodology. Selected variables were further assessed using a Plackett Burman screening study. A response surface design consisting of the critical factors was used to study the interactions between the study variables. Formulation variable X2: median particle size of budesonide (D50) (µ) has strikingly influenced dissolution (%) (Y1), while D50 droplet size distribution (µm) (Y2) was significantly impacted by formulation variable X1: Avicel RC 591 (%) and process variable X4: homogenization speed (rpm). A design space plot within which the CQAs remained unchanged was established at lab scale. A comprehensive approach for development of B-NS product based on the QbD methodology has been demonstrated. The accuracy and robustness of the model were confirmed by comparability of the predicted value generated by model with the observed value.