Researchers have long wished to be able to couple this carbon based
solid�state NMR technique with one that looks at hydrogen nuclei. It
has been possible to look at hydrogen when the sample is a solution (solution-state
NMR) but this is not as easy in solid-state NMR as the extensive
network of coupled together 1H nuclei leads to broad lines in the
spectrum that are hard to tell apart. This makes it almost useless
when you are examining a tablet. Tablets are also particularly
difficult to examine as the active drug within the tablet is combined
with a mixture of other filler compounds (excipients).
This breakthrough by the Warwick team opens up hydrogen nuclei to
useful study by solid-state NMR which will bring immense benefits to
the study of polymorphism in drugs and organic molecules in general.
This is because hydrogen atoms are central to hydrogen bonding (as
opposed to carbon atoms which "observe" from afar). Hydrogen bonding
is often the driving force in determining how organic molecules do
differ in their methods of "3D packing" forming polymorphs or
pseudo-polymorphs (pseudo-polymorphism referring to crystal structures
that differ through the inclusion or non inclusion of small molecules,
eg with or without water). This new NMR technique can identify which
pseudo polymorph of an active pharmaceutical is present in a complete
tablet.
The research team led by Dr Steven Brown from the University of
Warwick�s Department of Physics have exploited recent developments in
NMR hardware and pulse sequence design allowing them to gain
high-resolution 1H solid-state NMR spectra by a method called CRAMPS (combined
rotation and multiple-pulse spectroscopy). By using this
high-resolution two-dimensional 1H CRAMPS solid-state NMR they
obtained a spectrum for a tablet formulation in less than 2 hours,
which is equivalent to the time required for a good 13C CP MAS one
dimensional spectrum.
Dr Steven Brown said: "This Hydrogen 1H solid-state NMR method gives
powerful new insight that complements established Carbon 13C based
techniques - this new approach should be adopted as a routine tool in
pharmaceutical characterisation"
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