Structural and Dynamical Properties of Indomethacin Molecules
embedded within the Mesopores of Silicates and Metal-Organic
Framework Materials: a Solid-State NMR View
Gregor Mali, Tomaž Čendak
National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia.
e-mail: gregor.mali@ki.si
Mesoporous silicates and metal-organic materials comprise two extremely
interesting families of materials that exhibit promising properties for several
fields of application including catalysis, gas separation and storage, and heat
storage. In the field of pharmaceutical science and technology these materials
are especially interesting as matrices for the drug-delivery systems, which can
improve release of poorly soluble drugs. While many studies exist that test the
feasibility of preparation of delivery systems from various mesoporous matrices
and various model drugs, the atomic-scale studies of drugs embedded within the
mesopores are rather rare. In this presentation we will try to demonstrate that
solid-state NMR spectroscopy is a unique tool for studying the structural
properties of the mesoscopically confined drug and for studying the drug-drug
and drug-matrix interactions. We will also try to explain that knowledge about
drug-matrix interactions is very important, because the interactions crucially
determine the rate of the release of drug from the delivery system.
The presentation will focus on our investigation of model drug-delivery
systems prepared from SBA-15 mesoporous silicate matrix, and MIL-101 and
MIL-53 metal-organic frameworks loaded with different amounts of
indomethacin. In the SBA-15-based drug-delivery systems NMR spectroscopy
indicates that only when concentration of indomethacin within the mesopores
exceeds a certain value, hydrogen bonds between the drug molecules become
abundant. Nitrogen sorption analysis and comparison of 1H spin-lattice relaxation
times in progressively loaded SBA-15 matrices suggest that above such loading
concentration rigid nanoparticles that extend throughout the entire mesopore
cross-section start to form. 1H-13C CPMAS NMR spectrum of indomethacin
embedded within the mesopores of SBA-15 closely resembles the spectrum of
the bulk amorphous indomethacin and does not allow drawing firm conclusions
about the molecular conformation and the packing of the drug molecules within
the pores. On the contrary, variable-temperature 1H spin-lattice relaxation
measurements show that the mesoscopically confined indomethacin is
significantly different from the bulk amorphous indomethacin. It does not
become rubbery and is, regarding the mobility of the drug molecules, much more
similar to the crystalline form of indomethacin. In MIL-101- and MIL-53-based
drug-delivery systems the NMR measurements also show that the solvent
molecules, used during the drug-loading procedure, attach to the frameworks by
hydrogen bonds and cannot be removed from the pores by gentle drying. This
makes the mesoporous metal-organic matrices less convenient for the drug
delivery than mesoporous silicates.
Figure 1. NMR spectroscopy uses atomic nuclei as probes that provide
information about their local environment. In this way it enables the inspection of
the drug-drug and drug-matrix interactions in drug-delivery systems based on
mesoporous silicates and metal-organic materials.