Nondestructive Investigation of the Agglomeration and Sedimentation Process for Nanosuspensions via NMR Relaxation of Water Molecules

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15970
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: University of Toyama
• Principal Investigator: Okada Kotaro 富山大学, 薬学部, 客員助教 (70842962)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: NMR / T2緩和時間 / 医薬品 / ナノ粒子 / 凝集 / 沈降 / 懸濁液 / 低磁場NMR

Outline of Final Research Achievements

This study investigated an agglomeration and sedimentation of nanoparticles in a suspension using nuclear magnetic resonance (NMR) relaxation. The nanosuspension was prepared by wet bead milling using indomethacin and polyvinylpyrrolidone.
In this study, we focused on the water molecules, not nanoparticles, and obtained the T2 relaxation time (T2) of the water molecules using the low-field NMR instrument. During the storage period at 25°C from 0 to 24 h, the T2 value rapidly increased at the beginning of the storage. After that, the rapid increase in T2 values slowed down at ca. 4 hours.
In a suspension system, because the T2 value of water molecules is known to reflect the surface area of the particle, the observed rapid increase in T2 value indicated an agglomeration of nanoparticles. Therefore, it was shown that the measurement of T2 relaxation of a nanosuspension could evaluate the agglomeration and sedimentation process.

Free Research Field

物理薬剤学

Academic Significance and Societal Importance of the Research Achievements

本研究成果の学術的意義は、固体状態である薬物粒子の物理化学的な安定性を評価する際に、薬物粒子を直接評価せず、媒体である水のT2緩和測定を通じて、薬物粒子の安定性を間接的に評価した点にある。水分子のT2緩和を観測対象とすることで、薬物の種類に依存しない、汎用的な薬物粒子の凝集および沈降の評価方法となる。
また、低磁場型のNMR装置を用いて、薬物ナノ懸濁液の安定性評価におけるT2緩和測定の有用性を示した点に、社会的意義がある。低磁場型のNMR装置は、永久磁石を有するベンチトップ型であるため、医薬品の製造プロセスにおける品質評価への応用が期待できる。