Preparation of liposomes at large scale using the ethanol injection method: Effect of scale-up and injection devices
Preparation of liposomes at large scale using the ethanol injection method: Effect of scale-up and injection devices
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DOI：
10.1016/j.cherd.2014.09.008
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发表时间：
2015-02-01
影响因子：
3.9
通讯作者：
Fessi, Hatem
中科院分区：
文献类型：
--
作者：
Charcosset, Catherine;Juban, Audrey;Fessi, Hatem
在本研究中，使用乙醇注射技术制备脂质体，体积为60 mL至3 L。已经测试了具有不同规模和注射装置的实验装置：（1）使用注射器进行注射的装置;（2）使用两个泵通过Shirasu多孔玻璃（SPG）膜注射有机相和水相的实验装置;（3）使用浸入水相中的管注射有机相的中试装置;（4）使用两个泵将有机相和水相注入通过SPG膜的中试装置。通过透射电子显微镜（TEM）表征所获得的脂质体制剂的大小、多分散指数（PDI）、zeta电位和形态。已经测试了两种制剂：无药物脂质体制剂和负载α-生育酚的脂质体制剂。对于这两种制剂，结果表明，所有的实验设置都适合于制备具有窄尺寸分布的小囊泡，具有良好的重现性和稳定性。使用注射用膜的中试装置改善了有机相到水相中的微观混合，从而优化了制备时间。在中试装置上直接进行的乙醇蒸发具有简单和连续过程的优点。(C)2014化学工程师学会。Elsevier B. V.出版，保留所有权利。
In the present study, the preparation of liposomes using the ethanol injection technique was reported for volumes from 60 mL to 3 L. Experimental set-up with different scales and injection devices have been tested: (1) a device using a syringe for injection; (2) an experimental set-up using two pumps for injecting both organic and aqueous phases through a Shirasu Porous Glass (SPG) membrane; (3) a pilot plant using a tube dipping into the aqueous phase for injection of the organic phase; (4) a pilot plant using two pumps for injection of both organic and aqueous phases through the SPG membrane. The liposome preparations obtained were characterized for their size, polydispersity index (PDI), zeta potential, and morphology by transmission electronic microscopy (TEM). Two formulations have been tested: drug-free liposome formulation and a-tocopherol-loaded liposome formulation. For both formulations, it was shown that all experimental set-ups were appropriate for the preparation of small vesicles having narrow size distributions, with good reproducibility and stability. The pilot plant using a membrane for injection improves micromixing of the organic phase into the aqueous phase and therefore optimizes the preparation time. Evaporation of ethanol performed directly on the pilot plant has the advantages of being an easy and continuous process. (C) 2014 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.