Online quality control with Raman spectroscopy in pharmaceutical tablet manufacturing

Abstract

Quality testing for tablet composition and uniformity at the manufacturing stage is critical to the pharmaceutical industry. However, current off-line, destructive, wet chemistry analysis incurs significant costs and long test times. This paper introduces a methodology to form a population batch size for quality control sampling in tablet manufacturing for an alternative online testing technology, Raman spectroscopy. An approach is presented to determine the minimum testing batch size for quality control sampling based on the desirable confidence level, margin of error, testing rate, and production rate. Experiments with both traditional wet chemistry analysis and Raman spectroscopy are conducted. The results demonstrate that the quality of Raman spectroscopy is comparable to that of wet chemistry analysis. The proposed quality sampling methodology reduces the queue time by orders of magnitude for typical tablet batches of one to four million tablets awaiting test results following the tablet compaction process. Furthermore, it increases the tablet sample size, which subsequently raises the confidence level.