Exploring the crystallisation of aspirin in a confined porous material using solid-state nuclear magnetic resonance

Abstract

In this study, nuclear magnetic resonance (NMR) is used to investigate the crystallisation behaviour of aspirin within a mesoporous SBA-15 silica material. The potential of dynamic nuclear polarisation (DNP) experiments is also investigated using specifically designed porous materials that incorporate polarising agents within their walls. The formation of the metastable crystalline form II is observed when crystallisation occurs within the pores of the mesoporous structure. Conversely, bulk crystallisation yields the most stable form, namely form I, of aspirin. Remarkably, the metastable form II remains trapped within the pores of mesoporous SBA-15 silica material even 30 days after impregnation, underscoring its persistent stability within this confined environment.

Fig. 1. Schematic representation of the crystallisation of aspirin within the pores of mesoporous SBA-15 silica material (with or without wall-embedded TEMPO radicals). The mesoporous silica material is impregnated with a solution of aspirin in ethanol (0.8 M). Evaporation of solvent (ethanol) leads to crystallisation of aspirin within the pores of the material.

Fig. 2. (a) ¹³C CPMAS NMR spectrum recorded for a mesoporous SBA-15 silica material without wall-embedded TEMPO radicals and impregnated at room temperature with a solution of aspirin in ethanol (0.8 M). The spectrum was recorded 2 days after impregnation. (b) ¹³C CPMAS NMR spectrum recorded for a powder sample of aspirin subsequently obtained from a solution of aspirin in ethanol. (c) ¹³C CPMAS NMR spectrum of commercial aspirin. All spectra were recorded without microwave irradiation and at a temperature of 98 K. Signals labelled with “*” correspond to spinning side bands.

Fig. 3. ¹³C NMR resonances corresponding to the methyl group of the aspirin spectrum (blue curve) recorded at 98 K on a mesoporous SBA-15 silica material 2 days after impregnation with a solution of aspirin in ethanol (0.8 M). The Gaussian peaks used for the deconvolution are shown as filled grey shapes and their sum is shown as a dotted purple line. The 3 Gaussian peaks correspond to the individual ¹³C NMR resonances of the amorphous phase (Am), and the crystalline phases of form I and II of aspirin.

Fig. 4. T _1ρ-filtered ¹³C CPMAS NMR spectrum recorded on a mesoporous SBA-15 silica material impregnated with a 0.8 M solution of aspirin in ethanol. This experiment was recorded 2 days after material impregnation, without microwave irradiation and at a temperature of 98 K. Signals labelled with “*” correspond to spinning side bands. The ¹³C NMR chemical shift of the methyl group signal of forms I and II are at 19.8 ppm and 20.9 ppm, respectively.