Raman spectroscopy and chemometrics for pharmaceutical process analysis
Abstract
This thesis describes new applications of non-destructive and non-invasive Raman spectroscopy for pharmaceutical process analysis. Raman spectroscopy, with its high degree of informational content, remote sampling capability and simplicity, promises to be a good candidate for the understanding of pharmaceutical processes and quality monitoring. In results presented here, Raman spectroscopy was used as a new technique to determine tablet content uniformity (CU), coating thickness and crystallization and polymorphic transitions of mannitol during freeze-drying. In the CU study, a low resolution Raman spectrometer was utilized for rapid on-line determination of acetaminophen content in a small batch of tablets. Additionally, sampling statistics were reviewed in an effort to determine how many tablets should be assayed for specific batch sizes. The low resolution Raman spectrometer instrument was also utilized in the development of a multivariate calibration curve aimed to determine tablet-coating thickness. To avoid sub-sampling issues due to sample inhomogeneity, this Raman system employs a revolving focus, which increases the sampled volume. Non-invasive monitoring of mannitol crystallization and polymorphic transitions during freeze-drying was achieved by coupling a long working distance high-resolution Raman spectrometer to a freeze-drier. This high-resolution system offers a beam size diameter of 6 mm, which allows sampling a surface area 1600 times larger than conventional probes. By employing principal component analysis (PCA) to the spectroscopic data, it was possible to extract valuable information pertaining to water and mannitol crystallization points and the polymorphic form of mannitol.
Degree
Ph.D.
Advisors
Taylor, Purdue University.
Subject Area
Analytical chemistry|Pharmacology|Pharmaceuticals
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