Detection of Crystalline Ibuprofen Components in Ibuprofen-Loaded SBA-15 Mesoporous Silica Using Time-Domain NMR

The present study evaluated the applicability of time-domain NMR (TD-NMR) for detecting crystalline ibuprofen components in ibuprofen-loaded mesoporous silica. Ibuprofen-loaded mesoporous silica samples with different drug loadings were prepared, and the physical state of ibuprofen was characterized by nitrogen adsorption, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), ¹³C solid-state NMR spectroscopy, and TD-NMR relaxation measurements. PXRD, DSC, and ¹³C solid-state NMR spectroscopy did not clearly detect crystalline ibuprofen in samples with ibuprofen loadings of 10-30%. By contrast, crystalline components were observed in samples with loadings of 40% or higher. These crystalline components were considered to originate predominantly from excess ibuprofen that crystallized outside the mesopores. In the T₁ relaxation analysis using TD-NMR, IBU10-30 was mainly described by a monoexponential function, whereas IBU40-70 required a biexponential function, yielding a long T₁ component associated with crystalline ibuprofen. In the T₂ relaxation analysis, IBU40-70 exhibited an initial rapid decay that was described by a Gaussian function, whereas IBU10-30 showed a gradual exponential decay. The signal proportions of these NMR relaxation components increased with increasing ibuprofen loading and showed trends consistent with the apparent crystallinity estimated by DSC. These results suggest that TD-NMR, particularly T₂ relaxation analysis, may serve as a complementary, nondestructive, and rapid method for evaluating the appearance and increase of crystalline ibuprofen components in mesoporous silica formulations and for monitoring changes in crystallinity.