Merck Respiratory Product Development, 556 Morris Avenue, S7-A2-2123, Summit, NJ 07901, United States.
J Pharm Biomed Anal. 2011 Apr 5;54(5):1013-9. doi: 10.1016/j.jpba.2010.12.007. Epub 2010 Dec 14.
The purpose of this research was to demonstrate the utility of Raman spectroscopy for process analysis of a suspension metered dose inhaler manufacturing process. Chemometric models were constructed for the quantification of ethanol and active pharmaceutical ingredient such that both could be monitored in real-time during the compounding and filling operations via tank measurements and recirculation line flow-cell measurements. Different spectral preprocessing techniques were used to delineate the effects of mixing speed and temperature changes from actual concentration effects. Raman spectroscopy offers advantages in time savings and quality of information over the standard methods of analysis for respiratory formulations, such as a drug content assay via HPLC and ethanol testing via GC. The successful implementation of this work will allow formulation scientists to quantitatively assess both the formulation (e.g., the concentration of active pharmaceutical ingredient (API) and ethanol), as well as the manufacturing process (e.g., determination of mixing endpoints) in real-time.
本研究旨在展示拉曼光谱在混悬计量吸入器制造过程分析中的应用。构建了化学计量学模型，用于定量分析乙醇和活性药物成分，以便在混合和填充操作过程中通过罐测量和再循环线流通池测量实时监测这两种成分。使用不同的光谱预处理技术来区分混合速度和温度变化的影响与实际浓度变化的影响。与呼吸制剂的标准分析方法（如 HPLC 测定药物含量和 GC 测定乙醇）相比，拉曼光谱在节省时间和提高信息质量方面具有优势。这项工作的成功实施将使配方科学家能够实时定量评估配方（例如活性药物成分 (API) 和乙醇的浓度）和制造过程（例如混合终点的确定）。
