85 research outputs found
Dependence of the fragility of a glass former on the softness of interparticle interactions
We study the influence of the softness of the interparticle interactions on
the fragility of a glass former, by considering three model binary mixture
glass formers. The interaction potential between particles is a modified
Lennard-Jones type potential, with the repulsive part of the potential varying
with an inverse power of the interparticle distance, and the attractive
part varying with an inverse power . We consider the combinations (12,11)
(model I), (12,6) (model II) and (8,5) (model III) for (q,p) such that the
interaction potential becomes softer from model I to III. We evaluate the
kinetic fragilities from the temperature variation of diffusion coefficients
and relaxation times, and a thermodynamic fragility from the temperature
variation of the configuration entropy. We find that the kinetic fragility
increases with increasing softness of the potential, consistent with previous
results for these model systems, but at variance with the thermodynamic
fragility, which decreases with increasing softness of the interactions, as
well as expectations from earlier results. We rationalize our results by
considering the full form of the Adam-Gibbs relation, which requires, in
addition to the temperature dependence of the configuration entropy, knowledge
of the high temperature activation energies ino rder to determine fragility. We
show that consideration of the scaling of the high temperature activation
energy with the liquid density, analyzed in recent studies, provides a partial
rationalization of the observed behavior
Sliding and translational diffusion of molecular phases confined into nanotubes
The remaining dynamical degrees of freedom of molecular fluids confined into
capillaries of nano to sub-nanometer diameter are of fundamental relevance for
future developments in the field of nanofluidics. These properties cannot be
simply deduced from the bulk one since the derivation of macroscopic
hydrodynamics most usually breaks down in nanoporous channels and additional
effects have to be considered. In the present contribution, we review some
general phenomena, which are expected to occur when manipulating fluids under
confinement and ultraconfinement conditions.Comment: 17 pages, 8 fig
Pressure dependence of the crystallization rate for the S-enantiomer and a racemic mixture of ibuprofen
This paper examines the pressure effect on the
crystallization rate of the pharmaceutically active enantiomerically
pure S-enantiomer and the racemic mixture of the well-known drug
ibuprofen. Performed experimental studies revealed that at ambient
pressure S-ibuprofen crystallizes faster than the racemic mixture.
When the pressure increases, the crystallization rate slows down for
both systems, but interestingly it is more apparent in the case of the
S-enantiomer. It is found that this experimentally observed trend
can be understood based on the predictions of the classical
nucleation theory. We suggest that the solid−liquid interfacial free
energy is the main reason for the observed variations in S- and RS-ibuprofen’s stability behaviors. Employing a special method of
computational studies, i.e., the capillary fluctuation method, we show that the increase in pressure affects the solid−liquid interfacial
free energy for S- and RS-ibuprofen in an entirely different way. Importantly, the detected differences correspond to the
experimentally observed variations in the overall crystallization rates
Evidence of Strong Guest–Host Interactions in Simvastatin Loaded in Mesoporous Silica MCM-41
Funding Information: This research was funded by the Associate Laboratory for Green Chemistry LAQV, which is financed by national funds from FCT/MEC (UID/QUI/50006/2019) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER—007265). This research was funded by the Interreg 2 Seas program 2014–2020, and co-funded by the European Regional Development Fund (FEDER) under subsidy contract 2S01-059_IMODE and 2S07-033_ Site Drug. This research was funded by the Program PHC PESSOA 2018 project nbr 4340/40868R. This research was funded by National Funds through FCT—Portuguese Foundation for Science and Technology, reference UIDB/00100/2020, UIDP/00100/2020, LA/P/0056/2020, UIDB/50025/2020-2023, and PTNMR (ROTEIRO/0031/2013; PINFRA/22161/2016), co-financed by ERDF through COMPETE 2020, Portugal, POCI and PORL and FCT through PIDDAC (POCI-01-0145-FEDER-007688). M.C.C. acknowledges PTNMR&i3N for the researcher contract. T. Cordeiro acknowledges Fundação para a Ciência e a Tecnologia (FCT) for the scholarship SFRH/BD/114653/2016. I. Matos acknowledges FCT for the Investigator FCT contract IF/01242/2014/CP1224/CT0008. Publisher Copyright: © 2023 by the authors.A rational design of drug delivery systems requires in-depth knowledge not only of the drug itself, in terms of physical state and molecular mobility, but also of how it is distributed among a carrier and its interactions with the host matrix. In this context, this work reports the behavior of simvastatin (SIM) loaded in mesoporous silica MCM-41 matrix (average pore diameter ~3.5 nm) accessed by a set of experimental techniques, evidencing that it exists in an amorphous state (X-ray diffraction, ssNMR, ATR-FTIR, and DSC). The most significant fraction of SIM molecules corresponds to a high thermal resistant population, as shown by thermogravimetry, and which interacts strongly with the MCM silanol groups, as revealed by ATR-FTIR analysis. These findings are supported by Molecular Dynamics (MD) simulations predicting that SIM molecules anchor to the inner pore wall through multiple hydrogen bonds. This anchored molecular fraction lacks a calorimetric and dielectric signature corresponding to a dynamically rigid population. Furthermore, differential scanning calorimetry showed a weak glass transition that is shifted to lower temperatures compared to bulk amorphous SIM. This accelerated molecular population is coherent with an in-pore fraction of molecules distinct from bulklike SIM, as highlighted by MD simulations. MCM-41 loading proved to be a suitable strategy for a long-term stabilization (at least three years) of simvastatin in the amorphous form, whose unanchored population releases at a much higher rate compared to the crystalline drug dissolution. Oppositely, the surface-attached molecules are kept entrapped inside pores even after long-term release assays.publishersversionpublishe
Quelques exemples de modélisation moléculaire appliquée aux matériaux d'intérêt pharmaceutique
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Proteins: in silico approaches
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Molecular dynamics simulation of ibuprofen glass-forming liquid
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Structure and dynamics in ibuprofen glass-forming liquids
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Transition vitreuse et état vitreux dans les matériaux moléculaires: les "autres" verres !
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