Quality by design (QbD) approach for design and development of drug-device combination products: a case study on flunisolide nasal spray

Abstract

The objective of the present study was to design and develop drug-device combination product in particular flunisolide nasal spray (FNS) using quality by design (QbD) approach. Quality target product profile (QTPP) of FNS was defined and critical quality attributes (CQAs), i.e. viscosity (cp) (Y₁) and D₅₀ droplet size distribution (DSD) (μm) (Y₂) were identified. Potential risk factors were identified using a fish bone diagram and failure mode effect analysis (FMEA) tools. Plackett–Burman and Box–Behnken designs were used for screening the significant factors and optimizing the variables range, respectively. It was observed that viscosity (cp) (Y₁) was significantly impacted by formulation variables X₁: propylene glycol (PG) (%) and X₂: polyethylene glycol (PEG) 3350 (%), while D₅₀ DSD (μm) (Y₂) was significantly impacted by formulation variables X₁: PG (%), X₂: PEG 3350 (%) and device variable X₈: delivery volume (μl). A design space plot within which the CQAs remained unchanged was established at laboratory scale. In conclusion, this study demonstrated how QbD based development approach can be applied to the development of drug-device combination products with enhanced understanding of the impact of formulation, process and device variables on CQAs of drug-device combination products.

Keywords:

• Quality by design
• drug-device combination products
• nasal sprays
• design of experiments
• risk assessment
• pharmaceutical development

Acknowledgements

The authors wish to thank Dr. Ambikanandan Misra, Professor, Faculty of Pharmacy, The M.S. University of Baroda, Vadodara, India and Wockhardt Research Centre, Aurangabad (M.S.), India for providing constant support and enthusiasm to complete this work.

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper.