Analytical Research & Development, MRL, Merck & Co., Inc., West Point, PA 19486, USA.
Process Research & Development, MRL, Merck & Co., Inc., West Point, PA, 19486, USA.
Analyst. 2022 Jan 31;147(3):378-386. doi: 10.1039/d1an01797g.
Adjuvants are commonly employed to enhance the efficacy of a vaccine and thereby increase the resulting immune response in a patient. The activity and effectiveness of emulsion-based adjuvants has been heavily studied throughout pharmaceuticals; however, there exists a lack in research which monitors the formation of a stable emulsion in real time. Process analytical technology (PAT) provides a solution to meet this need. PAT involves the collection of data, thereby providing real time information about the monitored process as well as increasing understanding of that process. Here, three separate PAT tools - optical particle imaging, particle analysis, and Raman spectroscopy - were used to monitor two key steps involved in the formation of a stable emulsion product, emulsification and homogenization, as well as perform a stability assessment. The obtained results provided new insights-particle size decreases during emulsification and homogenization, and molecular changes do not occur during either the emulsification or homogenization steps. Further, the stability assessment indicated that the coarse emulsion product obtained from the emulsification step is stable over the course of 24 hours when mixed. To the best of our knowledge, this is the first report of an analytical methodology for , real time analysis of emulsification and homogenization processes for vaccine adjuvants. Using our proposed analytical methodology, an improved understanding of emulsion-based vaccine adjuvants can now be achieved, ultimately impacting the ability to develop and deliver successful pharmaceuticals.
佐剂常用于增强疫苗的功效，从而提高患者的免疫反应。乳剂佐剂的活性和有效性在整个制药行业都得到了广泛研究；然而，缺乏实时监测稳定乳剂形成的研究。过程分析技术（PAT）提供了满足这一需求的解决方案。PAT 涉及数据收集，从而提供有关监测过程的实时信息，并提高对该过程的理解。在这里，三种独立的 PAT 工具——光学粒子成像、粒子分析和拉曼光谱——用于监测稳定乳剂产品形成过程中的两个关键步骤，即乳化和均化，并进行稳定性评估。获得的结果提供了新的见解——在乳化和均化过程中，粒径减小，并且在乳化或均化步骤中都不会发生分子变化。此外，稳定性评估表明，当混合时，从乳化步骤获得的粗乳液产品在 24 小时内是稳定的。据我们所知，这是首次报道用于疫苗佐剂乳化和均化过程的实时分析的分析方法。使用我们提出的分析方法，可以更深入地了解基于乳剂的疫苗佐剂，最终影响开发和提供成功药物的能力。
