Development of ipratropium bromide and budesonide thixotropic nasal spray using quality by design approach

Abstract

The aim of this study was to develop combination suspension type nasal spray product for treatment of rhinorrhoea using quality by design (QbD) approach. Nasal corticosteroid Budesonide is effective in reducing the severity of congestion and sneezing. Anti-cholinergic Ipratropium bromide shows faster onset of action and reduce the duration of rhinorrhoea. Hence it will improve patient compliance, increase residence time, improve utilization of dose, and require less frequency of dose. Quality target product profile (QTPP) of test product Ipratropium Bromide and Budesonide nasal suspension was defined, and critical quality attributes (CQAs) were identified. Critical formulation, process and delivery device variables were recognised. Risk assessment was performed by using failure mode and effect analysis (FMEA) methodology. Selected variables were further assessed using a Plackett Burman screening study. Box Behnken design consisting of the critical factors was used to study the interactions between the study variables. Particle size of Budesonide (D50) (µ) (Formulation variables) has strikingly influenced viscosity (cP), while D50 Droplet size distribution (µm) was significantly impacted by Polymer concentration (%) (Formulation variables) and Homogenization speed (rpm) (process variable).