Solid-State Nuclear Magnetic Resonance Spectroscopy-Pharmaceutical Applications

Tishmack, Patrick A.; Bugay, David E.; Byrn, Stephen R.

doi:10.1002/jps.10307

Cited by 195 publications

(162 citation statements)

References 220 publications

(250 reference statements)

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“…Solid-state NMR is a powerful tool for characterising structure and dynamics in molecular solids such as pharmaceuticals [6][7][8][9][10][11][12]. Figure 1 shows previously reported [13] 13 C spectra of the materials relevant to this work: (b) the CPMAS spectrum of diformoterol fumarate diethanolate, (c) and (d) the CPMAS and "direct excitation" (DE) MAS spectra respectively of form C obtained by desolvation of the ethanolate.…”

Section: Introductionmentioning

confidence: 99%

NMR characterisation of dynamics in solvates and desolvates of formoterol fumarate

Apperley

Markwell

Frantsuzov

et al. 2013

Phys. Chem. Chem. Phys.

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Publisher's copyright statement:Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. ABSTRACT Solid-state NMR is used to characterise dynamics in the ethanol solvate of the pharmaceutical material formoterol fumarate and its associated desolvate. Jump rates and activation barriers for dynamic processes such as phenyl ring rotation and methyl group rotational diffusion are derived from 1D-EXSY and 13 C spin-lattice relaxation times respectively. 2 H and 13 C spin-lattice relaxation times measured under magic-angle spinning conditions are used to show that the fumarate ion in the desolvate is undergoing smallamplitude motion on a frequency scale of 100s of MHz at ambient temperature with an activation parameter of about 32 kJ mol -1 . Exact calculations of relaxation times under MAS provide a simple and robust means to test motional models in cases where relaxation rate maxima are observed, including for systems where the crystal structure of the material is unknown.

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Section: Introductionmentioning

confidence: 99%

NMR characterisation of dynamics in solvates and desolvates of formoterol fumarate

Apperley

Markwell

Frantsuzov

et al. 2013

Phys. Chem. Chem. Phys.

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“…In amorphous (glassy) carbohydrates, molecular conformations are statically distributed, and the CPMAS spectra often display heterogeneous line broadening, the chemical shift distributions reflecting the underlying conformational distributions [8][9][10][11][12]. Those broad lines often exhibit discontinuities and asymmetric features, and therefore provide much more information to be confronted to structural models, than a single averaged chemical shift value as measured in solution.…”

Section: Introductionmentioning

confidence: 99%

Exploring the conformational energy landscape of glassy disaccharides by cross polarization magic angle spinning C13 nuclear magnetic resonance and numerical simulations. II. Enhanced molecular flexibility in amorphous trehalose

Lefort

Bordat

Cesàro

et al. 2007

The Journal of Chemical Physics

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“…For the characterization of organic substances, the remarkable sensitivity of the 13 C chemical shift to local modulations of electronic density has made this technique one of the best probes of conformational aspects. In particular, 13 C CPMAS (cross polarization magic angle spinning) appears to be well adapted for studying poly-(or poorly) crystalline solids, revealing qualitative and quantitative features such as identification of phases and structural changes in crystalline polymorphs of pharmaceutical molecules (92)(93)(94). Recently, the development of proper analysis methods to measure relative amorphous and crystalline fractions has raised considerable interest (90,95).…”

Section: Ss-nmrmentioning

confidence: 99%

Methods of amorphization and investigation of the amorphous state

Einfalt¹,

Planinšek²,

Hrovat³

2013

Acta Pharmaceutica

117

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.g., polymorphs) provides pharmaceutical scientists with an opportunity to select the preferred form of the material to be used in a formulation. This is very useful since critical properties, such as particle morphology and dissolution properties, are frequently different in the different physical forms of a material. The amorphous form of pharmacologically active materials has received considerable attention because, in theory, it represents the most energetic solid state of a material, and should thus provide the biggest advantages in terms of dissolution rate and bioavailability (1). However, the amorphous form also shows various disadvantages, such as lower physical stability compared to crystals.The structure of an amorphous solid is usually described as possessing a crystal--like short-range molecular arrangement, but lacking a long-range order. As illustrated by Fig. 1, the immediate environment of a molecule (m) in an amorphous solid may not differ significantly from that in a crystal (e.g., similar number of and distance to nearest neighbors), but an amorphous solid lacks any long-range transational-orientational symmetry that characterizes a crystal (1). However, this is only true when we are dealing The amorphous form of pharmaceutical materials represents the most energetic solid state of a material. It provides advantages in terms of dissolution rate and bioavailability. This review presents the methods of solid--state amorphization described in literature (supercooling of liquids, milling, lyophilization, spray drying, dehydration of crystalline hydrates), with the emphasis on milling. Furthermore, we describe how amorphous state of pharmaceuticals differ depending on the method of preparation and how these differences can be screened by a variety of spectroscopic (X-ray powder diffraction, solid state nuclear magnetic resonance, atomic pairwise distribution, infrared spectroscopy, terahertz spectroscopy) and calorimetry methods.

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Solid-State Nuclear Magnetic Resonance Spectroscopy-Pharmaceutical Applications

Cited by 195 publications

References 220 publications

NMR characterisation of dynamics in solvates and desolvates of formoterol fumarate

NMR characterisation of dynamics in solvates and desolvates of formoterol fumarate

Exploring the conformational energy landscape of glassy disaccharides by cross polarization magic angle spinning C13 nuclear magnetic resonance and numerical simulations. II. Enhanced molecular flexibility in amorphous trehalose

Methods of amorphization and investigation of the amorphous state

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