Development of a novel one-step production system for injectable liposomes under GMP
Development of a novel one-step production system for injectable liposomes under GMP
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DOI：
10.1080/10837450.2017.1290106
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发表时间：
2018-01-01
影响因子：
3.4
通讯作者：
Minamino, Tetsuo
中科院分区：
文献类型：
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作者：
Araki, Ryo;Matsuzaki, Takashi;Minamino, Tetsuo
在良好的生产规范(GMP)下生产注射用脂质体的方法很少。GMP规定的注射用脂质体生产工艺一般包括脂质体形成、粒径均质、有机溶剂去除、脂质体浓度控制和灭菌。然而，这些复杂而独立的过程使得保持可伸缩性、重复性和无菌性变得困难。为了克服这些限制，我们开发了一种新颖的一步直列式封闭式脂质体生产系统，通过将直列式热混合设备与改进的逆流透析相结合，集成了所有生产过程。为了验证系统的有效性，我们制备了脂质体环孢素A(Lipo-CsA)，并对脂质体进行了冷冻干燥。三个独立的中试批次重复性好，均通过了注射用药的质量标准，证明该系统可以在GMP下使用。加速稳定性试验表明，脂质体在长期储存过程中是稳定的。这种一步法系统有助于在GMP下实现完全自动化和无人值守的可注射脂质体生产。
There are few methods available for injectable liposome production under good manufacturing practices (GMP). Injectable liposome production processes under GMP generally consist of liposome formation, size homogenization, organic solvent removal, liposome concentration control and sterilization. However, these complicated and separate processes make it difficult to maintain scalability, reproducibility and sterility. To overcome these limitations, we developed a novel one-step in-line closed liposome production system that integrated all production processes by combining the in-line thermal mixing device with modified counterflow dialysis. To validate the system, we produced liposomal cyclosporine A (Lipo-CsA) and lyophilized the liposomes. The three independent pilot batches were highly reproducible and passed the quality specifications for injectable drugs, demonstrating that this system could be used under GMP. The accelerated stability test suggested that the liposomes would be stable in long-term storage. This one-step system facilitates a fully automated and unattended production of injectable liposomes under GMP.