Chapter 2. Solid‐State NMR in Drug Discovery and Development

35Cl dynamic nuclear polarization solid-state NMR of active pharmaceutical ingredients

“…Solid APIs are commonly characterized using X-ray diffraction (powder or single-crystal), 1 H and 13 C solid-state NMR (SSNMR), thermogravimetric methods, and other spectroscopic techniques. [12][13][14][15][16][17][18] In many cases, these techniques provide adequate characterization of the bulk forms of APIs; however, they are often of limited use for dosage forms (especially those with low weight percentages, wt%, of the API). In particular, both pXRD patterns and 13 C SSNMR spectra of dosage forms often display interfering signals from the excipient (e.g., binding ingredients and fillers), which obscure signals arising from the API.…”

Structural and Dynamic Properties of Amorphous Solid Dispersions: The Role of Solid-State Nuclear Magnetic Resonance Spectroscopy and Relaxometry

“…In this review, the use of the term “spectroscopy” will be used to the measurements intended to yield the spectral properties (experimental observables that can be determined from spectra), whereas “relaxometry” will be referred to all the techniques concerning the measurement of nuclear relaxation times. These techniques have been proven as one of the supreme tools for elucidating the physical structure of ASD with the maximum details among the existing techniques . Expeditious application of SS‐NMR techniques for the identification, characterization, and quantification of various solid forms of drug candidates (polymorphs, hydrate, solvate, salt, cocrystal, amorphous, mesomorphous, etc.)…”

“…For example, it has been shown that T 1 relaxations originate from the local dynamics of side chains, whereas T 1ρ comes from the backbone motions of amorphous polymers such as lyophilized methylcellulose and polyvinylpyrrolidone (PVP) . Variable‐temperature nuclear relaxation time measurements overall can probe the molecular mobility whose onset is possibly well below the calorimetric glass transition and that is possible perpetrator for the long‐term stability problem of ASD …”

Ultrafast 1H MAS NMR Crystallography for Natural Abundance Pharmaceutical Compounds

“…Solid state nuclear magnetic resonance (SSNMR) spectroscopy is ubiquitously employed for the characterization of solid-phase pharmaceuticals, both pure molecules and complex formulations [1][2][3] . The span of SSNMR applications of pharmaceuticals varies from the identification of polymorphs and phase transitions to the assessment of formulation stability and homogeneity [4][5][6][7] .…”

“…Solid state nuclear magnetic resonance (SSNMR) spectroscopy is ubiquitously employed for the characterization of solid-phase pharmaceuticals, both pure molecules and complex formulations. − The span of SSNMR applications of pharmaceuticals varies from the identification of polymorphs and phase transitions to the assessment of formulation stability and homogeneity. − One of the greatest strengths of SSNMR for the analysis of pharmaceutical products is that long-range order, such as present in crystals, is not required.…”