Complexation of Budesonide in Cyclodextrins and Particle Aerodynamic Characterization of the Complex Solid Form for Dry Powder Inhalation

Abstract

The purpose of this study is to evaluate the effect ofbudesonide-cyclodextrins (CDs) complex formation in thein-vitro aerodynamic properties of the dry powder producedfor pulmonary delivery. Phase-solubility studies were performedusing budesonide and β-CD, DM-β-CD and HP-β-CD.The complex budesonide:DM-β-CD revealed the highest stabilityconstant (K_s = 3339.7 ± 4.76%; n = 3) and the solid powder was prepared by spray-drying.Complexation was evidenced by Differential Scanning Calorimetry (DSC). A physical mixture of budesonide and DM-β-CD was prepared for use as reference. The fine particle fraction and particle size distribution of both powders were assessed using Twin Stage Liquid Impinger (TSLI) and Aerosizer®LD, respectively. The content uniformity of the capsules filled (sd); (n) was 191.8 (± 2.74) μg; (10) for the budesonide:DM-β-CD solid complex and 204.9 (± 9.35) μg; (10) for the physical mixture. The emitted dose (rsd); (n) was 68.0% (± 26.1%); (5) of the nominal dose (solid complex) and 70.6% (± 12.6%); (5) (physical mixture). The fine particle fraction was 67.7% (± 18.9%); (5) of the emitted dose (solid complex) and 39.8% (± 16.9%); (5) (physical mixture). While no statistically significant difference was observed between the emitted dose means of both the solid complex and physical mixture, a statistically significant higher fine particle fraction mean was obtained for the solid complex. The results suggest that using a spray-dried CD complex powder for pulmonary drug delivery may increase the drug's respirable fraction and consequently its therapeutic efficacy.