(19) F NMR Spectroscopy as a Highly Sensitive Method for the Direct Monitoring of Confined Crystallization within Nanoporous Materials.
The introduction of fluorine into the structure of pharmaceuticals has been an effective strategy for tuning their pharmacodynamic properties, with more than 40 new drugs entering the market in the last 15 years. In this context, (19) F NMR spectroscopy can be viewed as a useful method for investigating the host-guest chemistry of pharmaceuticals in nanosized drug-delivery systems. Although the interest in confined crystallization, nanosized devices, and porous catalysts is gradually increasing, understanding of the complex phase behavior of organic molecules confined within nanochambers or nanoreactors is still lacking. Using (19) F magic-angle-spinning NMR spectroscopy, we obtained detailed mechanistic insight into the crystallization of flufenamic acid (FFA) in a confined environment of mesoporous silica materials with different pore diameters (3.2-29 nm), providing direct experimental evidence for the formation of a molecular-liquid-like layer besides crystalline confined FFA form I.
School of Pharmacy, University of East Anglia, Norwich, UK.|Department of Drug Form Technology, Faculty of Pharmacy, Wroclaw Medical University, ul. Borowska 211, 50-556, Wroclaw, Poland.
Karol P
KP
Nartowski
School of Pharmacy, University of East Anglia, Norwich, UK.
Diksha
D
Malhotra
School of Pharmacy, University of East Anglia, Norwich, UK.|Drug Product Science and Technology, Bristol-Myers Squibb, Reeds Lane, Moreton, Merseyside, CH46 1QW, UK.
Lucy E
0000-0003-1718-4937
LE
Hawarden
Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.|F. Hoffmann-La Roche A. G., 4070, Basel, Switzerland.
Juraj
J
Sibik
UK 850 MHz Solid-State NMR Facility, Department of Physics, Millburn House, University of Warwick, Coventry, CV4 7AL, UK.
Dinu
0000-0001-9315-8250
D
Iuga
Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
J Axel
0000-0002-4958-0582
JA
Zeitler
School of Pharmacy, University of East Anglia, Norwich, UK.
László
0000-0002-2087-4501
L
Fábián
School of Pharmacy, University of East Anglia, Norwich, UK. Y.Khimyak@uea.ac.uk.
Yaroslav Z
0000-0003-0424-4128
YZ
Khimyak
drug delivery; flufenamic acid; mesoporous silica; nanocrystals; solid-state NMR spectroscopy