プロセス解析を目指した時間領域nmrを基盤とする製剤の物性評価

Abstract

Here, we sought to investigate the usefulness of time-domain NMR (TD-NMR) for evaluating the physical properties of drug formulations. TD-NMR measures NMR relaxation and is mainly performed using a bench-top low-field NMR system (e.g., 20 MHz); thus, it does not require any specific sample shape for measurement if the sample is not gas. Taking advantage of these features, TD-NMR has been widely used for quality control in food science. However, it has rarely been used in the pharmaceutical field. The T 1 and T 2 relaxations are not spectra like those obtained by a high-field NMR system (e.g., 300-600 MHz) but only curves in which the NMR signal recovers or decays according to a specific rule. Therefore, selecting the equation used in the fitting analysis is crucial to estimate the time constants, T 1 and T 2 relaxation times. As the result of a series of studies, the T 1 relaxation measurement by TD-NMR was shown to help evaluate the crystallinity of drugs in solid dosage forms and the miscibility of a drug and excipient in a binary mixture. The T 2 relaxation measurement was also helpful for quantitatively evaluating the solid form of drugs in a physical mixture with or without moisture adsorption. TD-NMR is an excellent technique widely applied to evaluating the physical properties of various formulations, whether solid or liquid, and is expected to be applied to process analysis and quality control in the pharmaceutical field.