Applications of terahertz spectroscopy to pharmaceutical sciences

The application of terahertz pulsed spectroscopy within the US Food and Drug Administration's (FDA's) recent process analytical technology (PAT) initiative is considered. As a case study the potency levels in paracetamol (4-acetamidophenol) and aspirin (acetylsalicylic acid) test tablets have been recovered from the terahertz absorption spectra using a multivariate partial-least-squares (PLS) calibration model. Root-mean-square errors of cross-validation (RMSECVs) of 2.85% and 3.90% were obtained for paracetamol and aspirin, respectively. Information about other excipients can also be obtained; for example, using the strong lactose absorption lines in the tablets, RMSECVs of 3.65% and 4.30% could be recovered from the paracetamol and aspirin samples, respectively. As active ingredients may also change their solid-state form during formulation processing or storage and as this can adversely affect the final dosage performance, monitoring of pharmaceutical ingredients is essential for a 'right-first-time' philosophy within the industry. Terahertz pulse spectroscopy is a high-throughput technique with many areas of potential exploitation in the pharmaceutical industry; these issues are discussed in this paper.