Title :

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

Author(s) :

Cordeiro, Teresa [Auteur]
Universidade Nova de Lisboa = NOVA University Lisbon [NOVA]
Matos, Inês [Auteur]
Universidade Nova de Lisboa = NOVA University Lisbon [NOVA]
Danede, Florence [Auteur]
Unité Matériaux et Transformations - UMR 8207 [UMET]
Sotomayor, João C. [Auteur]
Universidade Nova de Lisboa = NOVA University Lisbon [NOVA]
Fonseca, Isabel M. [Auteur]
Universidade Nova de Lisboa = NOVA University Lisbon [NOVA]
Corvo, Marta C. [Auteur]
CENIMAT/I3N
Dionísio, Madalena [Auteur]
Universidade Nova de Lisboa = NOVA University Lisbon [NOVA]
Viciosa, María Teresa [Auteur]

Affouard, Frédéric [Auteur]
Unité Matériaux et Transformations - UMR 8207 [UMET]
T. Correia, Natália [Auteur]
Unité Matériaux et Transformations (UMET) - UMR 8207

Journal title :

Pharmaceutics

Abbreviated title :

Pharmaceutics

Volume number :

15

Pages :

1320

Publisher :

MDPI AG

Publication date :

2023-04-22

ISSN :

1999-4923

HAL domain(s) :

Physique [physics]/Matière Condensée [cond-mat]/Science des matériaux [cond-mat.mtrl-sci]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS
INRAE
ENSCL

Collections :

• Unité Matériaux et Transformations (UMET) - UMR 8207

Research team(s) :

Matériaux Moléculaires et Thérapeutiques

Submission date :

2023-12-11T13:29:20Z
2023-12-13T09:03:14Z