Inhalable clarithromycin liposomal dry powders using ultrasonic spray freeze drying

Inhalable clarithromycin liposomal dry powders using ultrasonic spray freeze drying

Tiantian Yea, Jiaqi Yub, Qiuhua Luoa, Shujun Wanga, Hak-Kim Chanb


Liposomal dry powder inhalation for the pulmonary administration has a great potential to improve the efficacy of antibiotics while reducing adverse effects. To improve aerosolisation efficiency of liposomal dry powders, we prepared clarithromycin liposomal powder formulations (CLA-Lips-DPIs) by an ultrasonic spray freeze drying (USFD) method using 15% mannitol and 5% sucrose (W:V) as combination lyoprotectants (co-lyoprotectants). The formulation had a porous structure, comprising micron-sized particles with uniform drug content and high drug recovery. Co-lyoprotectants could modulate the liposomal powder from absorbing moisture, resulting in moisture absorption being < 15% (W/W) when stored at 75% relative humility for 2 h. The interaction of CLA, lyoprotectant and lipids of CLA-Lips-DPIs was investigated by differential scanning calorimetry. The reconstituted liposome suspension showed a high entrapment efficiency of up to 80% and a narrow size distribution due to the co-lyoprotectants protection. CLA-Lips-DPIs formulations remained unchanged after 3-month storage at 60% RH and 25 °C with a high aerosol efficiency (emitted dose > 85%, fine particle fraction 43%–50%). These results demonstrated the aerosolisation efficiency and storage of the CLA-Lips-DPIs formulation. Liposomal powder formulations prepared by USFD can potentially be an effective drug delivery system for delivering antibiotics.


Ultrasonic spray freeze drying; Liposomes; Clarithromycin; Dry powder inhaler (DPI); Inhalation aerosols; Aerosolisation efficiency