Confinement in mesoporous silica can greatly increase the solubility of pharmaceutical compounds. Propionic acid derivatives (a very popular class of drugs that include ibuprofen and ketoprofen) would greatly benefit from such technology, given their common apolar character. However, it is still debated whether, after confinement, these drugs are adsorbed on the pore walls as individual molecules or they keep the H-bonded dimeric structure that exists in their crystalline form. Their physical state inside the mesopores could have important consequences on the final performances of the drug delivery system. We employed accurate periodic density functional theory simulations, both static and dynamic, to investigate the issue. We simulated ibuprofen, as a model for all propionic acid derivatives, adsorbed both as a monomer and as a dimer inside a realistic model for the MCM-41 mesoporous silica. We found that adsorption is energetically favored in both cases, driven by both vdW and H-bond interactions. However, through ab initio molecular dynamics, we observed a continuous forming, breaking and reforming of these interactions. In the end, by comparing computed energetics, vibrational spectra and mobility, we were able to provide some important clues on the physical state of this class of drugs inside mesoporous silica, helping to define which drug family (monomer or dimer) is more probable after confinement.

Propionic acid derivatives confined in mesoporous silica: monomers or dimers? The case of ibuprofen investigated by static and dynamic ab initio simulations

DELLE PIANE, MASSIMO;CORNO, MARTA;UGLIENGO, Piero
2016-01-01

Abstract

Confinement in mesoporous silica can greatly increase the solubility of pharmaceutical compounds. Propionic acid derivatives (a very popular class of drugs that include ibuprofen and ketoprofen) would greatly benefit from such technology, given their common apolar character. However, it is still debated whether, after confinement, these drugs are adsorbed on the pore walls as individual molecules or they keep the H-bonded dimeric structure that exists in their crystalline form. Their physical state inside the mesopores could have important consequences on the final performances of the drug delivery system. We employed accurate periodic density functional theory simulations, both static and dynamic, to investigate the issue. We simulated ibuprofen, as a model for all propionic acid derivatives, adsorbed both as a monomer and as a dimer inside a realistic model for the MCM-41 mesoporous silica. We found that adsorption is energetically favored in both cases, driven by both vdW and H-bond interactions. However, through ab initio molecular dynamics, we observed a continuous forming, breaking and reforming of these interactions. In the end, by comparing computed energetics, vibrational spectra and mobility, we were able to provide some important clues on the physical state of this class of drugs inside mesoporous silica, helping to define which drug family (monomer or dimer) is more probable after confinement.
2016
135
3
1
10
http://link.springer-ny.com/link/service/journals/00214/index.htm
AIMD; DFT; Drug delivery; Ibuprofen; Mesoporous silica; Propionic acid derivatives; Physical and Theoretical Chemistry
Delle Piane, Massimo; Corno, Marta; Ugliengo, Piero
File in questo prodotto:
File Dimensione Formato  
TCAC-S-15-00540_4aperto.pdf

Open Access dal 16/02/2017

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 1.71 MB
Formato Adobe PDF
1.71 MB Adobe PDF Visualizza/Apri
printed_paper.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 2.69 MB
Formato Adobe PDF
2.69 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1591955
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 8
social impact