Pharmaceutical compounds, SSNMR polymorphism

We will discuss the SSNMR most common experiments used to investigate pharmaceutical compounds, including one- and two-dimensional experiments and relaxation time measurements. Additionally, we will mention some aspects of first principle calculation. Also we highlight the importance of NMR as a multinuclear technique. We will focus on SSNMR applied for charaaerization of new developed active pharmaceutical compounds and formulated drugs. We will pay attention to some particular topics as polymorphism, complexes with cyclodextrin and an emerging issue in pharmaceutical industry as it is the development of cocrystals. NMR crystallography is also discussed. 

Keywords SSNMR, Pharmaceutical compounds. Characterization, NMR crystallography. Polymorphism, Complexes... 

In that regard, several reviews have been published showing the advances of SSNMR techniques appHed to polymers, zeolites, proteins, etc. [91,92]. In this section, we summarize the advances achieved in the past decade in SSNMR applied to polymorphism on pharmaceutical compounds. 

Indeed, when CP/MAS has become routinely employed in SSNMR characterization of pharmaceutical compounds, there are other nuclei, less used than the former, that can bring important and unique information when studding drugs in sohd form. One of these nuclei is Cl. The nuclear quadrupole resonance (NQR) has been widely used for polymorphism analysis [101,102], and in the past years, the use chlorine nuclei also started to be used in SSNMR experiments for polymorphism investigation. The NMR is an excellent probe of the Cl ion-binding envi-... 

Many pharmaceuticals are prepared as hydrochloride salts for reasons of solubility, crystallinity and/or stability. Schurko and coworkers describe the potential of Cl SSNMR spectroscopy as a tool for pharmaceutical hydrochloride polymorph fingerprinting and recognition [12,34]. By examining a large series of samples, it is shown that the chlorine EFG and CS tensors are generally distinct for each pharmaceutical compound, and for each polymorph. The authors also correlate the quadrupolar coupling parameters to the local hydrogen bond environment of the chloride ions and report several trends, some of which corroborate those reported previously [31,35]. 

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