The use of freeze-dried mannitol to enhance the in vitro aerosolization behaviour of budesonide from the Aerolizer®

•FDM enhanced the dispersion of a hydrophobic and a hydrophilic drug from DPI.•Carriers with a more elongated shape and a higher porosity generated higher FPFs.•BUD was electropositively charged whereas SS was electronegatively charged.•Leucine improved the flow and the aerosolization properties of FDM carrier.

The efficiency of drug delivery from drug-carrier dry powder inhaler (DPI) systems is typically low. The purpose of this study was to examine the aerosolization performance of a hydrophobic drug, budesonide (BUD), from DPI formulations containing a promising carrier, freeze-dried mannitol (FDM), and to compare the results to those obtained previously with a hydrophilic drug, salbutamol sulphate (SS).The results showed that, in comparison to the formulation containing commercial BUD and commercial lactose, a total of 3.8-fold increase in the fine particle fraction (FPF) was obtained from the formulation containing FDM (FPF: 7.5% versus 29%) whereas a total of 4.6-fold increase in the FPF was obtained from the formulation containing FDM and leucine additive (FPF: 35%). Regression analysis showed DPI formulations containing carrier particles with a more elongated/less spherical shape, a higher content of fine particulates (< 5 μm) and a higher porosity to produce higher FPFs of BUD.FDM promoted the aerosolization of budesonide intended for pulmonary delivery. The addition of leucine (by 4.8%, w/w) has further improved the flow and the aerosolization properties of FDM. FDM produced higher aerodynamic diameters and smaller FPFs of BUD as compared to SS, attributable to BUD having a higher electrostatic charge density and a higher agglomeration tendency than SS.

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