Investigation of the Relationship between the Chemical Stability of Itraconazole Adsorbed on Silica during Humidification and NMR Relaxation Using Time-Domain NMR

Kotaro Okada*, Myu Hirota, Shungo Kumada, Yoshirnori Onuki

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Silica powder is an essential pharmaceutical ingredient, which in some combinations with drugs, causes chemical instability of the drug adsorbed on it. NMR measurements have been used to determine the drug adsorption state; however, the relationship between drug chemical stability and NMR relaxation, one of the NMR processes, is yet to be thoroughly studied. This work investigated the relationship between the chemical stability of itraconazole (ITZ)-adsorbed silica and its NMR relaxation. NMR can specifically observe 1H nuclei, and this feature was exploited to study only the T1 relaxation of these nuclei in the drug, excluding the silica signal composed of Si and O. ITZ, a poorly water-soluble model drug, was physically adsorbed on nonporous silica (Aerosil 200, AER), and mesoporous silica (Sylysia 320), and the 1H T1 relaxation was measured before storage using the time domain (TD)-NMR technique. The amount of ITZ degradant adsorbed in the silicas was also measured after storage at humidified conditions. Then, the relationship between the degradant amount of ITZ-adsorbed silica after storage and the T1 relaxation rate (1/T1) before storage was investigated. The ITZ-adsorbed silicas showed a positive correlation between the degradant amount and the 1/T1 value. ITZ-adsorbed AER showed a strong positive correlation (R2=0.751). Thus, the 1/T1 value may be an efficient parameter to determine the chemical stability of ITZ adsorbed on nonporous silica. The 1/T1 value measurement by TD-NMR could provide new insight for evaluating the chemical stability of solid dosage forms containing silica.

Original languageEnglish
Pages (from-to)419-426
Number of pages8
JournalChemical and Pharmaceutical Bulletin
Volume73
Issue number5
DOIs
StatePublished - 2025/05

Keywords

  • NMR
  • amorphous
  • chemical stability
  • itraconazole
  • relaxation time
  • silica

ASJC Scopus subject areas

  • General Chemistry
  • Drug Discovery

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