QbD Assisted Development of Inhalable Spray-Dried Procubosomal Powder Intended to be used for Lung Delivery
Akash Deep & Vikas Rana
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala (Punjab), India
Summary
The primary objective of study was to optimize the parameters involved in development of inhalable spray-dried procubosomal powder (SDPP) using the spray drying process, with an aim to improved aerosolization performance and yield of formulation. The development of gefitinib (GFT) loaded-SDPP began with establishment of a quality target product profile and a thorough risk assessment by the Ishikawa diagram that identifies ten high-risk parameters to guide formulation development. Subsequently, the Taguchi design was employed to systematically screen different formulation parameters (glyceryl monooleate: poloxamer P407, polyethylene glycol 200 content, stirring temperature, stirring speed, stirring duration, mannitol: leucine) and process parameters (inlet temperature, outlet temperature, aspirator flow rate) along with equipment configuration parameter (cyclone design). These parameters were assessed based on their individual effects on critical quality attributes, i.e., yield (%), device removal efficiency (DRE, %), aerosolization efficiency (AE, %), and fine particle fraction (FPFTSI, %) of GFT-SDPP. The results revealed that optimized formulation achieved a satisfactory aerosolization performance, i.e., DRE of 94.2 ± 5.6%, AE of 52.2 ± 1.84%, FPFTSI of 63.8 ± 3.63% and yield of 32.5 ± 2.82%. This optimized formulation exhibited a mean median aerodynamic diameter (MMAD) of 3.29 ± 0.53 µm, enhanced FPFAC (60.83 ± 2.19%) and entrapment efficiency (96.2 ± 3.98%). SEM analysis indicated smooth spherical particles with somewhat wrinkled surface. The results of in-vitro dissolution studies indicated the sustained release of GFT from SDPP with enhanced dissolution. In conclusion, this study successfully developed an inhalable SDPP formulation, demonstrating promising potential as targeted drug delivery system.