Alam Md Anik, Shi Zhenqi, Drennen James K, Anderson Carl A
Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA, 15282, USA; Duquesne University Center for Pharmaceutical Technology, 600 Forbes Avenue, Pittsburgh, PA, 15282, USA.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
Int J Pharm. 2017 Jun 30;526(1-2):199-208. doi: 10.1016/j.ijpharm.2017.04.054. Epub 2017 Apr 23.
In-line monitoring of continuous powder flow is an integral part of the continuous manufacturing process of solid oral dosage forms in the pharmaceutical industry. Specifically, monitoring downstream from loss-in-weight (LIW) feeders and/or continuous mixers provides important data about the state of the process. Such measurements support control of the process and thereby enhance product quality. Near Infrared Spectroscopy (NIRS) is a potential PAT tool to monitor the homogeneity of a continuous powder flow stream in pharmaceutical manufacturing. However, the association of analytical results from NIR sampling of the powder stream and the homogeneity (content uniformity) of the resulting tablets provides several challenges; appropriate sampling strategies, adequately robust modeling techniques and poor sensitivities (for low dose APIs) are amongst them. Information from reflectance-based NIRS sampling is limited. The region of the powder bed that is interrogated is confined to the surface where the measurement is made. This potential bias in sampling may, in turn, limit the ability to predict the homogeneity of the finished dosage form. Further, changes to the processing parameters (e.g., rate of powder flow) often have a significant effect on the resulting data. Sample representation, interdependence between process parameters and their effects on powder flow behavior are critical factors for NIRS monitoring of continuous powder flow system. A transmission NIR method was developed as an alternative technique to monitor continuous powder flow and quantify API in the powder stream. Transmission NIRS was used to determine the thickness of the powder stream flowing from a loss-in-weight feeder. The thickness measurement of the powder stream provided an in-depth understanding about the effects of process parameters such as tube angles and powder flow rates on powder flow behaviors. This knowledge based approach helped to define an analytical design space that was specific to flow properties and to determine the optimum process parameters for successful quantitation of powder stream. A PAT method based on transmission NIRS was developed to monitor the homogeneity of API in a continuously flowing powder stream.
在线监测连续粉末流是制药行业固体口服制剂连续制造过程的一个组成部分。具体而言，对失重（LIW）进料器和/或连续混合器下游进行监测可提供有关工艺状态的重要数据。此类测量有助于控制工艺，从而提高产品质量。近红外光谱（NIRS）是一种潜在的过程分析技术（PAT）工具，可用于监测制药生产中连续粉末流的均匀性。然而，粉末流的近红外采样分析结果与所得片剂的均匀性（含量均匀度）之间的关联存在若干挑战；其中包括适当的采样策略、足够稳健的建模技术以及灵敏度较低（对于低剂量活性成分）等问题。基于反射的近红外光谱采样所获得的信息有限。被检测的粉末床区域仅限于进行测量的表面。这种采样中的潜在偏差可能反过来限制预测最终剂型均匀性的能力。此外，加工参数的变化（例如粉末流速）通常会对所得数据产生重大影响。样品代表性、工艺参数之间的相互依赖性及其对粉末流动行为的影响是近红外光谱监测连续粉末流系统的关键因素。开发了一种透射近红外方法作为监测连续粉末流并定量粉末流中活性成分的替代技术。透射近红外光谱用于确定从失重进料器流出的粉末流的厚度。粉末流的厚度测量有助于深入了解诸如管角度和粉末流速等工艺参数对粉末流动行为的影响。这种基于知识的方法有助于定义一个特定于流动特性的分析设计空间，并确定成功定量粉末流的最佳工艺参数。开发了一种基于透射近红外光谱的过程分析技术方法来监测连续流动粉末流中活性成分的均匀性。
