Preparation of nanosized Fluticasone Propionate nasal spray with improved stability and uniformity

Abstract

Transmucosal nasal delivery has been recognized as up-and-coming option for delivery of therapeutic compounds. However, the short residence time of the formulation within the nasal cavity coupled to its low permeability is regarded as the barrier to good bioavailability. To overcome those limitations, we developed a new formulation - nanosized Fluticasone Propionate (FP) nasal spray. High pressure homogenization (HPH) was employed to achieve effective particle size reduction. Latin square experimental design (LSED) was implemented for high pressure homogenization process. With optimized process conditions, the resulting particles were less than 250 nm in size. The aging effect in FP nanosuspensions after 30-day refrigerated storage was not considerable. However, for long-term storage, a combination of homogenization and lyophilization (HL) was required to acquire stable FP nanocystals. The crystallinity of FP was examined by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), and no alternation was observed before or after homogenization and lyophilization process. The finished nasal spray offered a more uniform drug content compared to marketed formulation, which ensure the consistency and reproducibility of dose delivery. The study confirmed the effectiveness of homogenization, the usefulness of Latin square design and the feasibility of nano nasal spray.