NMR ciała stałego : zastosowania w farmacji i diagnostyce medycznej

Some characteristic features, distinguishing NMR in solution and solid phase, are briefly described. The techniques of magic angle spinning, cross-polarization, as well as the experiments with variable cross-polarization time and dipolar-dephasing pulse sequences are illustrated. The spectra measured for solutions are frequently used as an aid in the assignment of solid-state ones. The differences Δ=δsolution-δsolid state are explained in terms of conformational effects (resulting from frozen intramolecular reorientation in the solids) and intra- and intermolecular interactions (hydrogen bonds and also short intermolecular contacts in the crystals). Solid-state NMR spectroscopy has become an important technique in the field of pharmaceutical sciences. Solid-state techniques are used for the characterization of pharmaceutical solids: drug substances and dosage forms (tablets) and their mutual interactions. Structural information on solid antibiotics (penicillin salts, erythromycin A, chloramphenicol and its derivatives), anticoagulants (warfarin, sintrom), antimalaria (artemizinin) or anxiolytic drugs (buspirone and its analogues) was obtained by the analysis of 13C CP MAS spectra. Frequently exploited area is polymorphism because pharmaceutical polymorphs can display different solubilities, dissolution rates and bioavailability. Polymorphic forms of steroids (testosterone, prednisolone, cortisone) and 4-azasteroids (finasteride) and of numerous other drugs (e.g. AZT, paracetamol, phenobarbital) have been detected. Solid-state NMR has thus an ability to differentiate polymorphs, determine asymmetry in the crystal unit cell and investigate molecular motions within the solids. MAS NMR spectra can be recorded for powdered tablets, enabling fast identification of the active substance. Few examples of forensic applications include "Extasy" and Viagra tablets. The technique ideally lends itself to the studies on drugexcipients interaction, possible conversions of the drug during processing and storage can be followed. Multinuclear solid state NMR is also useful in characterization of materials and tissues removed during surgery (bones, brain tumors, urinary stones).