Lindsay Sarah, Tumolva Olympia, Khamiakova Tatsiana, Coppenolle Hans, Kovarik Martin, Shah Sanket, Holm René, Perrie Yvonne
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.
Global Development, Janssen Pharmaceutica NV, a Johnson & Johnson Company, Turnhoutseweg 30, 2340 Beerse, Belgium.
Pharmaceutics. 2024 Sep 1;16(9):1159. doi: 10.3390/pharmaceutics16091159.
Microfluidic liposome production presents a streamlined pathway for expediting the translation of liposomal formulations from the laboratory setting to clinical applications. Using this production method, resultant liposome characteristics can be tuned through the control of both the formulation parameters (including the lipids and solvents used) and production parameters (including the production speed and mixing ratio). Therefore, the aim of this study was to investigate the relationship between not only total flow rate (TFR), the fraction of the aqueous flow rate over the organic flow rate (flow rate ratio (FRR)), and the lipid concentration, but also the solvent selection, aqueous buffer, and production temperature. To achieve this, we used temperature, applying a design of experiment (DoE) combined with machine learning. This study demonstrated that liposome size and polydispersity were influenced by manipulation of not only the total flow rate and flow rate ratio but also through the lipids, lipid concentration, and solvent selection, such that liposome attributes can be in-process controlled, and all factors should be considered within a manufacturing process as impacting on liposome critical quality attributes.
微流控脂质体生产为加快脂质体制剂从实验室环境到临床应用的转化提供了一条简化途径。使用这种生产方法，可以通过控制配方参数（包括所用脂质和溶剂）和生产参数（包括生产速度和混合比例）来调整所得脂质体的特性。因此，本研究的目的不仅是研究总流速（TFR）、水相流速与有机相流速之比（流速比（FRR））和脂质浓度之间的关系，还包括溶剂选择、水性缓冲液和生产温度之间的关系。为实现这一目标，我们采用温度，应用实验设计（DoE）并结合机器学习。这项研究表明，脂质体的大小和多分散性不仅受到总流速和流速比的影响，还受到脂质、脂质浓度和溶剂选择的影响，从而可以在生产过程中控制脂质体的属性，并且在制造过程中应考虑所有影响脂质体关键质量属性的因素。
