Inhaled ceftazidime dry powder developed using spray freeze drying technique
Rishi M. Shah1,2, Anlin Lyu1, Greg F. Walker1, Rajesh Katare2,3 & Shyamal C. Das1
1 School of Pharmacy, University of Otago, Dunedin 9054, New Zealand.
2 Department of Physiology, University of Otago, Dunedin 9016, New Zealand.
3 Department of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin 9016, New Zealand.
Summary
Pulmonary delivery is an attractive approach to the management and treatment of lung infections. The delivery of antibacterial agents directly to the lungs provides a high drug concentration to the site of action and reduces systemic toxicity. However, the number of approved inhalation antibiotics is minimal, necessitating the urgent need for new inhaled antibacterial compounds. The reformulation of existing drugs is a promising way to develop new inhaled therapeutics. Ceftazidime, a potent broad-spectrum antibiotic used to treat bacterial infections, was used as the model drug. This molecule exhibits poor aerosolisation properties and degradation. Among the several methods implemented for producing inhaled formulations, spray-freeze drying has recently gained significant attention as a promising formulation approach which can enhance the aerosolisation of ceftazidime formulation. Spray-freeze drying is a hybrid technique that produces highly porous and dispersible dry powders with relatively low aerodynamic diameters that are suitable for pulmonary administration. L-leucine was employed as an aerosolisation enhancer. The formulations were characterized using scanning electron microscopy, infrared spectroscopy, water content, drug content and in vitro aerosolisation performance. SEM analysis suggests that the use of L-leucine resulted in highly porous spherical particles. The powder had ⁓9% water content and a drug content of 94%. It was found that adding L-leucine to the ceftazidime formulation enhanced its fine particle fraction by 1.2-fold. This study demonstrates the advantage of L-leucine in improving the aerosolisation performance of spray-freeze-dried particles.