Nuclear magnetic resonance (NMR) spectroscopy has been applied for the analysis of pharmaceutical solids. The technique was shown to be an excellent tool with the ability to determine solid form, ...structure, and mobility in many different types of samples. Polymeric formulations containing isotopically-labeled peptides were investigated using both 13C and 15N solid-state NMR spectroscopy. Information on the local environment, preferential hydration, and mobility was obtained from formulations with a very low peptide loading level. A method for gauging the protonation state in solid-state formulations was also explored, using fumaric acid as a marker for 'pH' in the solid state. Prednisolone was formulated with cyclodextrin and microcrystalline cellulose, and the effects of formulation and processing variables were studied using 13C solid-state NMR spectroscopy. From the spectra acquired, it was possible to quantitate the amount of crystalline prednisolone remaining following formulation. The polymorphic form present in each formulation was readily identifiable, and a form change was detected in one formulation batch. A method to suppress unwanted excipient peaks on the basis of cross polarization dynamics was also demonstrated. The nature of the mechanochromism of piroxicam has been investigated. Using 13C solid-state NMR spectroscopy, it was possible to determine that a small population of piroxicam molecules became zwitterionic when a mechanical stress was applied. Even though piroxicam was in a disordered state, the NMR spectra allowed quantitation of this structural transition that was the root cause of the mechanochromism. Changes in spin-lattice relaxation times of lactose, aspirin, and vitamin C were investigated as a function of pharmaceutical processing. Relaxation times were significantly reduced in processed samples, even when no amorphous material was formed in the process. This indicated the presence of many crystal defects, which in turn may act as relaxation sinks to account for faster relaxation throughout the material. Relaxation times were also shown to be an indicator of long-term stability in similarly processed samples, with shorter relaxation times indicating greater reactivity. Solid-state NMR relaxation measurements could show which formulation and processing variables result in the most stable dosage forms before long-term stability studies are performed.
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