Inhalable hydrophilic molecule-loaded liposomal dry powder formulations using supercritical CO2-assisted spray-drying

Liposomes are known to be one of the most promising drug delivery systems for carrying and delivering biopharmaceuticals. Yet, both liposomes and biopharmaceuticals are susceptible to destabilization during storage, and thus require cold supply and efficient distribution chains. This drawback can be overcome, though, by converting liposomal suspension into solid form dosage capable of administration via different routes, including the lungs. In this work, we present a synergy between pharmaceutical and supercritical carbon dioxide technologies to assist in liposome drying. Liposomes, encapsulating 5(6)- carboxyfluorescein (CF) as a marker of the internal aqueous phase, were produced and then dried using supercritical CO2 - assisted spray-drying (SASD). CFloaded liposomal dry powder formulations were thus obtained. After resuspension in water to remove the trehalose, the liposomes maintained their structure and the CF encapsulation efficiency remained above 95 %. To optimize the process, a quality-by-design approach using the design of experiments tool was used. Then, the powders were submitted to storage stability assays at relative humidity of 4 %, 50 % and 78 % for 30 days. Results showed that the dry powder formulations were able to maintain liposome stability at relative humidity of 4 % and 50 % at 20 degrees C for 30 days.

Automated summary

Liposomes are a promising drug delivery system for biopharmaceuticals, however, they can destabilize during storage. Converting liposomal suspension into solid form can overcome this issue, as shown in this study utilizing pharmaceutical and supercritical carbon dioxide technologies. The dry powder formulations demonstrated stability at specific relative humidities, showing potential for long-term storage.