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.

Encapsualtion of pharmaceuticals inside nanoporous materials is of increasing interest due to their possible applications as new generation therapeutics, thernostic platforms or smart devices. Mesoporous silicas are leading materials to be used as nanohosts for pharmacueticals. Further development of new generation of nanoscale therapeutics requires complete understanding of the complex host-guest interactions of organic molecules confined in nanosized chambers at different length scales. In this context we present results showing control over formation and phase transition of nanosize crystals of model flexible pharmaceutical molecule tolbutamide confined inside 3.2 nm pores of the MCM-41 host. Using low loading levels (up to 30 wt. %) we were able to stabilise the drug in highly dynamic amorphous/disordered state or direct the crystallisation of 2 the drug into highly metastable nanocrystalline form V of tolbutamide (at loading levels of 40 and 50 wt. %), providing first experimental evidence for crystallisation of pharmaceuticals inside the pores as narrow as 3.2 nm.

The introduction of fluorine into the structure of pharmaceuticals has been an effective strategy for tuning their pharmacodynamic properties,w ith more than 40 new drugs entering the market in the last 15 years.I nt his context, 19 FNMR spectroscopyc an be viewed as au seful method for investigating the host-guest chemistry of pharmaceuticals in nanosized drug-delivery systems.A lthough the interest in confined crystallization, nanosized devices,a nd porous catalysts is gradually increasing,u nderstanding of the complex phase behavior of organic molecules confined within nanochambers or nanoreactors is still lacking. Using 19 Fm agicangle-spinning NMR spectroscopy, we obtained detailed mechanistic insight into the crystallization of flufenamic acid (FFA) in ac onfined environment of mesoporous silica materials with different pore diameters (3.2-29 nm), providing direct experimental evidence for the formation of amolecularliquid-like layer besides crystalline confined FFAform I.