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Inhalable hydrophilic molecule-loaded liposomal dry powder formulations using supercritical CO2 – assisted spray-drying
Journal of CO2 Utilization ( IF 7.7 ) Pub Date : 2021-09-14 , DOI: 10.1016/j.jcou.2021.101709
Clarinda Costa 1, 2 , Beatriz Nobre 1 , Ana Sofia Matos 3 , Ana Sofia Silva 4 , Teresa Casimiro 1 , Maria Luísa Corvo 2 , Ana Aguiar-Ricardo 1
Affiliation  

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). CF-loaded 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 °C for 30 days.



中文翻译:

使用超临界 CO2 辅助喷雾干燥的可吸入亲水分子负载脂质体干粉制剂

众所周知,脂质体是最有前途的用于携带和递送生物药物的药物递送系统之一。然而,脂质体和生物药物在储存过程中都容易不稳定,因此需要冷供应和高效的分销链。然而,通过将脂质体悬浮液转化为能够通过不同途径(包括肺)给药的固体形式剂型,可以克服这一缺点。在这项工作中,我们展示了制药和超临界二氧化碳技术之间的协同作用,以协助脂质体干燥。脂质体,封装 5(6)-羧基荧光素 (CF) 作为内部水相的标志物,制备,然后使用超临界 CO 2干燥- 辅助喷雾干燥 (SASD)。从而获得负载CF的脂质体干粉制剂。重新悬浮在水中以去除海藻糖后,脂质体保持其结构,CF 包封率保持在 95% 以上。为了优化过程,使用了使用实验设计工具的设计质量方法。然后,将粉末在 4%、50% 和 78% 的相对湿度下进行 30 天的储存稳定性测定。结果表明,干粉制剂能够在 4% 和 50% 的相对湿度下在 20°C 下保持脂质体稳定性 30 天。

更新日期:2021-09-14
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