Pharmaceutical compounds, SSNMR

The solid-state characterization of novel pharmaceutical compounds remains an important issue. Solid-state NMR is one of the techniques of choice to gain information when other techniques are not available. Knowledge of the molecular structure in the solid state can lead to better design and control the behaviour of the drug as it affects important properties such as solubility in aqueous medium. Many different NMR experiments can be performed to obtain either structural or dynamic information on very broad space and time ranges, respectively. Contrary to others techniques, not only crystalline material but also amorphous materials can be studied by SSNMR. These and other... 

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... 

The implementation of SSNMR techniques in pharmaceutical compounds rehes not only in the developments of new pulse sequences but also in technological improvements such as probes and high power sources. 

In the past 10 years, an important number of publications [6,36] have shown the use of SSNMR together with other spectroscopic techniques, to obtain the complete characterization of recendy developed pharmaceutical compounds. As an example, Bruno etal. [36] reported the appHcation of CP/MAS to tizoxanide. The CP/MAS spectra and the NQS spectra of the compounds allowed Bruno and co-workers to determine changes in the hydrogen bonds of the drug under study. They could identify the replacement of intramolecular H-bonding by intermolecular H-bonding. 

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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