Terahertz pulsed spectroscopy (TPS) and terahertz pulsed imaging (TPI) are two novel techniques for the physical characterization of pharmaceutical drug materials and final solid dosage forms, utilizing spectral information in the far infrared region of the electromagnetic spectrum. This review focuses on the development and performance of pharmaceutical applications of terahertz technology compared with other tools for physical characterization. TPS can be used to characterize crystalline properties of drugs and excipients. Different polymorphic forms of a drug can be readily distinguished and quantified. Recent developments towards a better understanding of the fundamental theory behind spectroscopy in the far infrared have been discussed. Applications for TPI include the measurement of coating thickness and uniformity in coated pharmaceutical tablets, structural imaging and 3D chemical imaging of solid dosage forms.

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.

Pulsed terahertz attenuated total reflection (ATR) spectra of solid materials and liquids covering the 10 cm⁻¹ to 120 cm⁻¹ (0.3 THz to 3.6 THz) region of the electromagnetic spectrum are recorded using a terahertz pulsed spectrometer and silicon ATR modules. Pulsed terahertz ATR measurements are completed nondestructively using small amounts of sample (typically 1 mg for solids) and no sample preparation. Many terahertz analyses can be run in rapid sequence, minimizing the analysis time.