Storage stability of inhalable, controlled-release powder formulations of ciprofloxacin nanocrystal-containing liposomes

Abstract

Novel inhalable and controlled release powder formulations of ciprofloxacin nanocrystals inside liposomes (CNL) were recently developed. In the present study, the storage stability of CNL powders consisting of lyoprotectant (i.e. sucrose or lactose), lipids, ciprofloxacin ( CIP ), and magnesium stearate or isoleucine was investigated. These powders were produced by spray drying, collected in a dry box at < 15% relative humidity (RH), then stored at room temperature and either 4 or 20 %RH. Liposomal integrity, CIP encapsulation efficiency (EE), in vitro drug release (IVR), aerosol performance, and solid-state properties were examined over six months. Sucrose CNL powder exhibited consistent liposomal integrity, aerosol performance, and controlled release of CIP over six months of storage at 4 %RH. However, storage of the powder at 20 %RH for the same period caused sucrose crystallization and consequently a significant drop in EE and aerosol performance (p-values <0.05), along with the IVR of CIP becoming similar to that of the non-crystalline CIP liposomal dispersions (f2 > 50). Lactose CNL maintained superior aerosol performance over the six months irrespective of the storage RH. However, liposomal instability occurred at both RHs within the first month of storage with a significant drop in EE and an increase in liposome size (p-values <0.05). Moreover, the IVR assay of CIP from lactose CNL showed a less controlled release and a substantial difference (f2 < 50) from its initial value after six months regardless of the storage RHs. In conclusion, dry powder inhalers of CNL were physiochemically stable in sucrose lyoprotectant when stored below 4 %RH at room temperature for six months.