title: Design and development of dry powder sulfobutylether-β-cyclodextrin complex for pulmonary delivery of fisetin.
abstract: This study has investigated complexation of fisetin, a natural flavonoid, with three types of cyclodextrins to improve its solubility. Sulfobutylether-β-cyclodextrin (SBE-β-CD) showed the highest complexation efficiency while maintaining the in vitro antioxidant activity of fisetin. Addition of 20%v/v ethanol in water improved the amount of solubilized fisetin in the complex 5.9-fold compared to the system containing water alone. Spray drying of fisetin-SBE-β-CD complex solution in the presence of ethanol produced a dry powder with improved aerosolization properties when delivered from a dry powder inhaler, indicated by a 2-fold increase in the fine particle fraction (FPF) compared to the powder produced from the complex solution containing water alone. The pitted morphological surface of these particles suggested a more hollow internal structure, indicating a lighter and less dense powder. Incorporation of 20%w/w leucine improved the particle size distribution of the powder and further increased the FPF by 2.3-fold. This formulation also showed an EC50value equivalent to fisetin alone in the A549 cell line. In conclusion, an inhalable dry powder containing fisetin-SBE-β-CD complex was successfully engineered with an improved aqueous solubility of fisetin. The dry powder may be useful to deliver high amounts of fisetin to the deep lung region for therapeutic purposes.
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom; School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia. Electronic address: noratiqah.mohtar.14@ucl.ac.uk.
authors.forename: Noratiqah
authors.initials: N
authors.lastname: Mohtar
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
authors.forename: Kevin M G
authors.initials: KM
authors.lastname: Taylor
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
authors.forename: Khalid
authors.initials: K
authors.lastname: Sheikh
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom. Electronic address: s.somavarapu@ucl.ac.uk.
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Somavarapu
mesh_terms: D000336:Aerosols; D000975:Antioxidants / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D005419:Flavonoids / Q000008:administration & dosage*; D044948:Flavonols; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D033362:Powder Diffraction; D011208:Powders; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000336:Aerosols; D000975:Antioxidants; D004337:Drug Carriers; D005419:Flavonoids; D044948:Flavonols; D011208:Powders; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; C017875:fisetin
keywords: A549 cell line; Fisetin; Leucine; Pulmonary delivery; Spray drying; Sulfobutylether-β-cyclodextrin