NMR Study of BA/FBA Cocrystal Confined Within Mesoporous Silica Nanoparticles Employing Thermal Solid Phase Transformation

In this work, we report drug-loading procedure based on the solid state thermal transformation of a physical mixture of two ingredients: mesoporous silica nanoparticles (MSN) and an organic cocrystal. This procedure, known as the melting method, allows loading of the guest species into the host pores with high yield and an equimolar ratio of both components of the cocrystal. The study was carried out with commercial MSNs (MCM-41 and SBA-15) and a cocrystal consisting of equimolar amounts of benzoic acid (BA) and fluorinated benzoic acid (FBA). The BA/FBA sample was obtained by grinding crystalline acids. The structural constraints and molecular dynamics of BA/FBA in the crystal lattice were characterized employing 19F magic angle spinning (MAS), 13C MAS, 1H very fast (VF) MAS with sample rotation at 60 kHz, 2D NMR, 19F–19F BABA, and 1H–19F HETCOR correlations. We conclude that the system is very rigid with short distances between intermolecular aromatic layers. In contrast, BA/FBA loaded into MCM-41 and SBA-15 is very mobile in a broad range of temperatures. The structure and molecular dynamics of the guest assembly trapped in the MSN pores was established by 1H MAS, 19F MAS, 1H–19F HOESY MAS and 19F T2′ relaxation time measurements as well as 2H MAS. We conclude that the filling factor for the melting method, defined as the ratio of BA/FBA to MSN (weight to weight), is much higher compared to those for commonly used wet procedures. These results show new perspectives for future applications of MSNs as carriers of pharmaceutical cocrystals.