Using Terahertz Reflectance Spectroscopy to Quantify Drug Substance in Tablets

Abstract

The purpose of this research is to investigate the applicability of terahertz (THz) reflectance spectroscopy for quantification of drug substance in tablets, so as to demonstrate the feasibility for applying this technique to tableting process monitoring. In order to acquire a suitable absorbance spectrum for this purpose, it was necessary to enhance the reflection intensity. By using an aluminum plate as a mirror at the opposite surface of the tablet, a reasonable absorbance spectrum could be acquired to reflect the bulk information of the tablet. To assess the limit of tablet thickness, linearity between the tablet thickness and the absorbance value was investigated using lactose and mannitol tablets. Since linearity was found within 0.75-5.0 mm for both tablets using 0.4 and 0.8 THz region, it was confirmed that THz reflectance spectroscopy is applicable to tablets within at least 5.0 mm thickness. Mannitol tablets containing sodium salicylate as the model drug substance were used to investigate the quantitative performance of this technique. It was confirmed that the established calibration model was acceptable for this quantification because of the root-mean-squared error of cross-validation (RMSECV) being 1.95%. In order to evaluate the applicability of this technique, content quantitative performance in double layered tablets having active and placebo layers were assessed. Since this calibration model achieved the root-mean-squared error of prediction (RMSEP) of 1.42% for the double layered tablets, this technique was considered feasible even if the drug substance is localized in the tablets.Key words terahertz; reflection; in-line monitoring; process analytical technology; tablet; sodium salicylateThe tablet is one of the popular dosage forms in pharmaceutics, and quantification of drug substance in drug product, including the content uniformity test, is a critical and mandatory quality assurance requirement in tablet manufacturing. Although a conventional HPLC method is the most popular technique for quantification, there are growing interests to examine alternative analytical techniques that are possible to measure drug products in-process with a nondestructive manner. These interests are also in line with the United States Food and Drug Administration (FDA) Process Analytical Technology (PAT) initiative and guidelines.1) As a well-known example of the alternative techniques, near infrared (NIR) spectroscopy is being extensively used for the quantification of drug substance as a PAT tool. 2-4)Typically, only 10-30 tablets are generally employed as the representative for batch manufacturing of several million tablets. In-line monitoring during the tableting process is expected to attain higher quality assurance than the traditional end-product testing, because quantification for each and every unit dose would be expected. A reflectance spectroscopy is usually employed as the in-line monitoring tool, because a detector of a transmission spectrometer cannot be installed into a rotary tableting machine to ...

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