The molecular mobility of ibuprofen confined to a mesoporous silica host (MCM-41) of 3.6 nm pore diameter is investigated by dielectric relaxation spectroscopy. It is confirmed that crystallization is suppressed; therefore, depending on the temperature, the guest exists in the glassy and supercooled state inside of the pores. A detailed relaxation map is provided where multiple processes are dynamically characterized, comprised of three processes that are also found for the bulk and two additional ones. The bulk-like processes include two secondary processes, a simple thermally activated one, a γ process and a Johari–Goldstein βJG process, and the one associated with the dynamic glass transition of molecules located in the pore center (α process). In confinement, all of these processes display deviations in its dynamical behavior relative to the bulk, the most dramatic one undergone by the α process, which exhibits Arrhenius-like temperature dependence upon approaching the glass transition instead of Vogel/Fulcher/Tammann/Hesse (VFTH) scaling as obeyed by the bulk. The two additional relaxations are associated with the dynamical behavior of hydrogen-bonded ibuprofen molecules lying in an interfacial layer near the pore wall, an S process for which the mobility is strongly reduced relative to the α process and a Debye-like D process for which the dynamics is closely correlated to the dynamics of the interfacial process, both exhibiting VFTH temperature dependencies. The comparison with the behavior of the same guest in the analogous host, SBA-15, with a higher pore diameter (8.6 nm) leads to the conclusion that the bulk-like mobility associated with the dynamic glass transition undergoes finite size effects being accelerated upon a decrease of the pore size with a concomitant reduction of the glass transition temperature relative to the bulk, 22 and 32 K, respectively, for the 8.6 and 3.6 nm pore diameters. The continuous decrease in the separation between the α- and βJG-trace with pore size decrease allows one to conclude that confined ibuprofen is a suitable guest molecule to test the Coupling Model that predicts a transformation of the α process into a βJG-mode under conditions of an extreme nanoconfinement. The overall behavior inside of pores is consistent with the existence of two distinct dynamical domains, originated by ibuprofen molecules in the core of the pore cavity and adjacent to the pore wall, from which a clear picture is given by molecular dynamics simulation.
The molecular mobility of condensed matter confined to nanometer dimensions can be dramatically changed from those of the bulk state in such a way that, when the guest is a drug, it can be advantageously used in pharmaceutical applications. We show by dielectric relaxation spectroscopy that the molecular mobility of the important ibuprofen drug embedded in nanoporous SBA-15 is significantly influenced by the confinement. An evidence of the existence of two families of molecules with different molecular mobilities is provided and investigated in their temperature dependence. One family is due to molecules close to the pores' center with a higher mobility compared with the bulk at low temperatures, and another family with slower dynamics originated from molecules interacting with the pore walls. The work reports the simultaneous manifestation of true confinement and surface effects in this nanostructured silica host for a drug. For future applications in drug delivery systems, the dynamics determined by the guest–host interplay and the one of the bulklike molecules can be tuned to achieve a desired release profile.
The molecular mobility of amorphous ibuprofen has been investigated by broadband dielectric relaxation spectroscopy (DRS) covering a temperature range of more than 200 K. Four different relaxation processes, labeled as α, β, γ, and D, were detected and characterized, and a complete relaxation map was given for the first time. The γ-process has activation energy Ea = 31 kJ·mol-1, typical for local mobility. The weak β-relaxation, observed in the glassy state as well as in the supercooled state was identified as the genuine Johari-Goldstein process. The temperature dependence of the relaxation time of the α-process (dynamic glass transition) does not obey a single VFTH law. Instead two VFTH regimes are observed separated by a crossover temperature, TB = 265 K. From the low temperature VFTH regime, a Tgdiel(t =100 s) = 226 K was estimated, and a fragility or steepness index m = 93, was calculated showing that ibuprofen is a fragile glass former. The D-process has a Debye-like relaxation function but the temperature dependence of relaxation time also follows the VFTH behavior, with a Vogel temperature and a pre-exponential factor which seem to indicate that its dynamics is governed by the α-process. It has similar features as the Debye-type process observed in a variety of associating liquids, related to hydrogen bonding dynamics. The strong tendency of ibuprofen to form hydrogen bonded aggregates such as dimers and trimers either cyclic or linear which seems to control in particular the molecular mobility of ibuprofen was confirmed by IR spectroscopy, electrospray ionization mass spectrometry, and MD simulations.