Cohesive, multicomponent, dense powder flow characterization by NIR.
Cohesive, multicomponent, dense powder flow characterization by NIR.
复制标题
通过 NIR 进行内聚、多组分、致密粉末流动表征。
DOI：
10.1016/j.ijpharm.2006.12.014
复制
发表时间：
2007
影响因子：
5.8
通讯作者：
L. Cartilier
中科院分区：
文献类型：
--
作者：
C. Benedetti;N. Abatzoglou;Jean;L. McDermott;G. Léonard;L. Cartilier
非充气粉末流在下游制药工艺中经常遇到。这样的流动发生在粉末压缩单元的入口处，并且它们的特性是非常令人感兴趣的，因为任何粉末团聚或分离都可能对最终固体口服剂型的质量有害。这项工作的目的是开发一种过程分析技术（PAT）的方法，近红外光谱（NIR）的基础上在线粉末流动表征的药物制剂。选择了一种伊曲康药物制剂用于研究。组装实验室规模的料斗系统以监测粉末流动行为。选择在线商业近红外Axsun光谱仪和探针来收集压缩前致密、多组分、非充气粉末流的在线光谱数据。收集流动甘露醇和药品混合物的光谱。特别设计的非接触式采样接口允许在不影响混合均匀性的情况下收集代表性工艺粉末流谱。为实验室制备的样品开发了偏最小二乘化学计量学模型，以定量测定流动粉末的活性药物成分（API）水平。静态样品光谱和流动纯甘露醇光谱证明具有高度的重现性。该模型的校准标准误差为API水平的2.95%，R2为0.991。流动混合物粉末光谱和API估计值显示与模型样品中观察到的变化一致。流动药物混合物的平均值接近API浓度，表明拟定程序在统计学上可接受。该模型被认为是非常有前途的，一些改进将导致其作为PAT工具在生产规模上的最终接受。
Non-aerated powder flows are frequently encountered in downstream pharmaceutical processes. Such flows occur at the entrance of powder compression units, and their characteristics are of great interest because any powder agglomeration or segregation can be detrimental to the quality of the final solid oral dosage form. This work was aimed at developing a process analytical technology (PAT) method, based on near-infrared spectroscopy (NIR) for the in-line powder flow characterization of pharmaceutical formulations. An Ibuprofen drug formulation was selected for study. A bench-scale hopper system was assembled to monitor powder flow behaviour. An in-line commercial NIR Axsun spectrometer and probe were chosen to collect in-line spectral data on dense, multicomponent, non-aerated powder flow prior to compression. Spectra were collected on flowing mannitol and pharmaceutical product blends. A specially designed, non-contact sampling interface allowed the collection of representative process powder flow spectra without affecting blend uniformity. A partial least squares chemometric model was developed for laboratory-prepared samples, to quantitatively determine the flowing powder's active pharmaceutical ingredient (API) level. Static sample spectra and flowing pure mannitol spectra proved to have a high degree of reproducibility. The model's standard error of calibration was 2.95% of the API level with a R2of 0.991. Flowing blend powder spectra and API estimates showed variations consistent with those seen in model samples. The average values for flowing pharmaceutical blends were close to the API concentration, indicating that the proposed procedure was statistically acceptable. The model is considered very promising, and some improvements would lead to its final acceptance at production scale as a PAT tool.