Quality by design (QbD) approach for design and development of drug-device combination products: a case study on flunisolide nasal spray.
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 D50droplet 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 variablesX1: propylene glycol (PG) (%) andX2: polyethylene glycol (PEG) 3350 (%), while D50DSD (μm) (Y2) was significantly impacted by formulation variablesX1: PG (%),X2: PEG 3350 (%) and device variableX8: 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.
a Wockhardt Research Centre, D-4, M.I.D.C , Aurangabad , India.
Swapnil Sharadkumar
SS
Chudiwal
b Y B Chavan College of Pharmacy , Dr. Rafiq Zakaria Marg , Aurangabad , India.
Mohamed Hassan G
MHG
Dehghan
D000465:Algorithms; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D004339:Drug Compounding; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D005446:Fluocinolone Acetonide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D008956:Models, Chemical; D059085:Nasal Sprays; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry; D014783:Viscosity
D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D005079:Excipients; D059085:Nasal Sprays; D005446:Fluocinolone Acetonide; D011092:Polyethylene Glycols; D019946:Propylene Glycol; C007734:flunisolide
Quality by design; design of experiments; drug-device combination products; nasal sprays; pharmaceutical development; risk assessment