Nano spray-dried pyrazinamide-l-leucine dry powders, physical properties and feasibility used as dry powder aerosols

Abstract

Objective: The aim of this study was to investigate the effect of adding l-leucine and using an ethanolic solvent on the physicochemical properties and aerodynamic behavior of nano spray-dried pyrazinamide (PZA)-l-leucine powders.

Materials and methods: A nano spray dryer was employed to prepare PZA-l-leucine powders. The physicochemical properties were evaluated using a scanning electron microscope (SEM), differential scanning calorimetry and X-ray diffraction. The Andersen cascade impactor was used to evaluate the in vitro aerosolization performance of the sprayed powders.

Results and discussion: The incorporation of l-leucine at 10% improved the percentage fine particle fraction (%FPF) in all ethanolic solvent formulations by up to nearly twofold (20.0–23.4%) compared to the normal spray-dried PZA of (8.8–13.0%). Changes in the particle density and morphology were also observed. The dense solid particles of PZA were completely converted to bulk hollow particles with a thin shell by increasing the l-leucine content up to 50%. Higher ethanol concentration resulted in larger dimensions of the hollow particle but did not directly affect the aerosolization performance. The co-spray dried PZA with 20% l-leucine in a 10% ethanol feed solvent gave the best aerosolization performance (FPF = 33.0%).

Conclusions: The co-spray dried PZA with a suitable l-leucine content using a nano spray drying technique could be applied to formulate the PZA DPI.

• Andersen cascade impactor
• dry powder inhaler
• lung delivery
• nano spray dryer
• tuberculosis

Acknowledgements

The authors would like to thank Dr. Brian Hodgeson for editing the article.

Declaration of interest

The financial support was from PSU National Research University and NANOTEC-PSU Excellence Center on Drug Delivery System. The authors report no declarations of interest.