Solid‐State NMR Studies of Pharmaceutical Systems

Geppi, Marco; Mollica, Giulia; Borsacchi, Silvia; Veracini, Carlo Alberto

doi:10.1080/05704920801944338

Cited by 156 publications

(213 citation statements)

References 231 publications

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“…Similarly, sitespecific relaxation rates have been measured for the four inequivalent methyl carbon environments in solid L-valine [24]. More detailed information on the local dynamics has been provided by variable-temperature measurements of relaxation as shown for some pharmaceuticals [9], including ibuprofen [25,26], and for methyl α-L-fucopyranose [27] and C 60 [28].…”

Section: C Spin-lattice Relaxation Times In Solidsmentioning

confidence: 99%

“…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%

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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: C Spin-lattice Relaxation Times In Solidsmentioning

confidence: 99%

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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“…22,31,32 SSNMR has the advantage of providing localised chemical information on the crystalline or amorphous state, unlike bulk methods such as DSC or PXRD. SSNMR was successfully employed to characterize different polymorphic and amorphous forms of other sartans (candesartan, irbesartan and losartan).…”

mentioning

confidence: 99%

“…Solid-state NMR (SSNMR) has been widely used to study molecular dynamics in pharmaceutics. [22][23][24][25] For example, Luthra et al studied changes in molecular dynamics of model drug systems during annealing by Differential Scanning Calorimetry (DSC) 26 and 13 C NMR relaxation times. 27 They observed that in most cases annealing leads to longer T 1 and T 1ρ NMR relaxation times, indicating a slowing of the local dynamics.…”

mentioning

confidence: 99%

Characterization of Two Distinct Amorphous Forms of Valsartan by Solid-State NMR

et al. 2015

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Valsartan (VAL) is an antihypertensive drug marketed in an amorphous form. Amorphous materials can have different physicochemical properties depending on preparation method, thermal history, etc., but the nature of such materials is difficult to study by diffraction techniques. This study characterizes two different amorphous forms of valsartan (AR and AM) using solid-state NMR (SSNMR) as a primary investigation tool, supported by solution-state NMR, FT-IR, TMDSC, and dissolution tests. The two forms are found to be clearly distinct, with a significantly higher level of structural arrangement in the AR form, as observed in 13C, 15N, and 1H SSNMR. 13C and 15N NMR indicates that the fully amorphous material (AM) contains an approximately equal ratio of cis–trans conformers about the amide bond, whereas the AR form exists mainly as one conformer, with minor conformational “defects”. 1H ultrafast MAS NMR shows significant differences in the hydrogen bonding involving the tetrazole and acid hydrogens between the two materials, while 15N NMR shows that both forms exist as a 1,2,3,4-tetrazole tautomer. NMR relaxation times show subtle differences in local and bulk molecular mobility, which can be connected with the glass transition, the stability of the glassy material, and its response to aging. Counterintuitively the fully amorphous material is found to have a significantly lower dissolution rate than the apparently more ordered AR material.

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“…2 Thus solvates, hydrates and both stoichiometric and non-stoichiometric lattice inclusion compounds are included in this definition. 3 With respect to the pure polymorphism phenomenon, co-crystal formation provides much more in terms 30 of possibilities for modulating crystal packing and this is due to the choice of two parameters: the co-former and the type of weak interaction. 4 The use of inorganic salts as co-formers has already been explored, by our group, as an effective method for producing ionic co-crystals and salt co-crystals of barbituric 35 acid.…”

mentioning

confidence: 99%

Improvement of the water solubility of tolfenamic acid by new multiple-component crystals produced by mechanochemical methods

Gaglioti¹,

Chierotti²,

Grifasi³

et al. 2014

CrystEngComm

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Tolfenamic acid (HTA) is a drug characterized by very poor water solubility (13.6 nM under acidic\ud conditions) and moderate solubility in ethanol (0.17 M). A series of new multicomponent crystals have been\ud obtained by applying mechanochemical methods (i.e. kneading) to mixtures of HTA with sodium acetate,\ud sodium carbonate, sodium hydroxide and imidazole. These reactions resulted in two salts (NaTA·0.5H2O\ud and NaTA HT Form), a co-crystal of salts (NaTA·HTA·0.5NaAc·2H2O) and two salt co-crystals\ud (NaTA·HTA·H2O/NaHCO3 and IMH-TA·HTA). Due to the lack of suitable crystals for single-crystal X-ray\ud diffraction analysis, the structural features of the samples have been characterized by solid-state NMR\ud (1H MAS, 13C CPMAS, 1H-13C FSLG LG-CP HETCOR and 15N CPMAS), IR(ATR) and Raman spectroscopy,\ud VT-XRPD and elemental analysis. The evaluation of thermal stability and dissolution behavior was\ud performed using thermogravimetry, differential scanning calorimetry and dissolution kinetic tests. The new\ud solid-state forms show better thermal stability than pure HTA and an improved dissolution rate, which is\ud most pronounced in NaTA·HTA·H2O/NaHCO3, NaTA HT Form and NaTA·0.5H2O

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Solid‐State NMR Studies of Pharmaceutical Systems

Cited by 156 publications

References 231 publications

NMR characterisation of dynamics in solvates and desolvates of formoterol fumarate

NMR characterisation of dynamics in solvates and desolvates of formoterol fumarate

Characterization of Two Distinct Amorphous Forms of Valsartan by Solid-State NMR

Improvement of the water solubility of tolfenamic acid by new multiple-component crystals produced by mechanochemical methods

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