How Molecular Mobility, Physical State, and Drug Distribution Influence the Naproxen Release Profile from Different Mesoporous Silica Matrices

Abstract

Aiming to evaluate how the release profile of naproxen (nap) is influenced by its physical state, molecular mobility, and distribution in the host, this pharmaceutical drug was loaded in three different mesoporous silicas differing in their architecture and surface composition. Unmodified and partially silylated MCM-41 matrices, respectively MCM-41 and MCM-41sil, and a biphenylene-bridged periodic mesoporous organic matrix, PMOBph, were synthetized and used as drug carriers, having comparable pore sizes (∼3 nm) and loading percentages (∼30% w/w). The loaded guest was investigated by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dielectric relaxation spectroscopy (DRS). DSC and XRD confirmed amorphization of a nap fraction incorporated inside the pores. A narrower glass transition was detected for PMOBph_nap, taken as an indication of the impact of host ordering, which also hinders the guest molecular mobility inside the pores as probed by DRS. While the PMOBph matrix is highly hydrophobic, the unmodified MCM-41 readily adsorbs water, accelerating the nap relaxation rate in the respective composite. In the dehydrated state, the faster dynamics was found for the silylated matrix since guest–host hydrogen bond interactions were inhibited to some extent by methylation. Nevertheless, in all the prepared composites, bulk-like crystalline drug deposits outside pores in a greater extent in PMOBph_nap. The DRS measurements analyzed in terms of conductivity show that, upon melting, nap easily migrates into pores in MCM-41-based composites, while it stays in the outer surface in the ordered PMOBph, determining a faster nap delivery from the latter matrix. On the other side, the mobility enhancement in the hydrated state controls the drug delivery in the unmodified MCM-41 matrix vs the silylated one. Therefore, DRS proved to be a suitable technique to disclose the influence of the ordering of the host surface and its chemical modification on the guest behavior, and, through conductivity depletion, it provides a mean to monitor the guest entrance inside the pores, easily followed even by untrained spectroscopists.

Controlled Sublimation Rate of Guest Drug from Polymorphic Forms of a Cyclodextrin-Based Polypseudorotaxane Complex and Its Correlation with Molecular Dynamics as Probed by Solid-State NMR

“…12 The release of naproxen from the unmodified and silylated MCM-41 matrix agreed well with its molecular mobility, as probed by the dielectric relaxation spectroscopy. 12 paramount significance to study the molecular dynamics of encapsulated APIs and their effect on the physical properties.…”

“…The 13 C and 1 H NMR spectra revealed that the order of SA mobility in the complexes is MC form ≫ HC form > TC form, which coincided with the order of its sublimation. Mobility of a guest compound encapsulated in a host structure such as CD or mesoporous silica can be affected by factors such as cavity size or pore diameter, pore matrix, host/guest interactions, and so on. − Generally, an increase in the cavity or pore size of the host compound has a direct effect on the molecular mobility of the guest compound . However, the mobility of SA could not be correlated to the host intermolecular space size, which is in the order of TC form > MC form ≥ HC form.…”

“…Dionísio and co-workers investigated the influence of the physical state, molecular mobility, and distribution of naproxen encapsulated in three different hosts (unmodified MCM-41, silylated by methyl capping MCM-41sil, and biphenylene-bridged silica matrix PMOBph) with similar pore size . The release of naproxen from the unmodified and silylated MCM-41 matrix agreed well with its molecular mobility, as probed by the dielectric relaxation spectroscopy . Thus, it is of paramount significance to study the molecular dynamics of encapsulated APIs and their effect on the physical properties.…”

“…The molecular state and dynamics of the guest API can be affected by various parameters such as cavity size or pore diameter, binding geometry, porous matrix and topology, and host/guest interaction. − Knapik et al revealed that the stability of amorphous ezetimibe incorporated in porous materials with different pore sizes was influenced by its molecular mobility, immobilization effect, and pore size . Dionísio and co-workers investigated the influence of the physical state, molecular mobility, and distribution of naproxen encapsulated in three different hosts (unmodified MCM-41, silylated by methyl capping MCM-41sil, and biphenylene-bridged silica matrix PMOBph) with similar pore size . The release of naproxen from the unmodified and silylated MCM-41 matrix agreed well with its molecular mobility, as probed by the dielectric relaxation spectroscopy .…”

Evidence of Strong Guest–Host Interactions in Simvastatin Loaded in Mesoporous Silica MCM-41

“…In this context, SIM-MCM-41 interactions were thoroughly investigated by ATR-FTIR, and the way it is distributed in the matrix was inferred by DSC and molecular dynamics (MD) simulations. MD provided a picture of SIM distribution and anchoring inside pores, which, together with the molecular mobility of the loaded drug, are critical factors that could perform a role in the release mechanism [ 40 ]. The dynamical behavior of loaded SIM was probed by dielectric relaxation spectroscopy (DRS) that monitors reorientational motions of permanent dipoles under the influence of an external oscillating electrical field [ 41 ].…”