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.




Chemistry, Multidisciplinary; Engineering, Chemical


Costa, C; Nobre, B; Matos, AS; Silva, AS; Casimiro, T; Corvo, ML; Aguiar-Ricardo, A

nossos autores


This work received financial support from PT national funds (FCT/MCTES, Fundacao para a Ciencia e Tecnologia and Ministerio da Cien-cia, Tecnologia e Ensino Superior) through the projects UIDB/50006/2020 & UIDP/50006/2020, UIDB/00667/2020, UID/DTP/04138/2020 & UIDP/04138/2020, UIDB/50011/2020 & UIDP/50011/2020 and PD/BD/142880/2018. The authors are grateful to Prof. M. F. Martins, Prof. M. Dionisio e Dr A. B. Pereiro for the Laser (R) Thermohygrometer data logger, differential scanning calorimetry and Karl-Fischer titration facilities, respectively.

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