Redetermination and H-atom refinement of (<i>S</i>)-(+)-ibuprofen. Corrigendum.

Hansen, Lars Kr.; Perlovich, German L.; Bauer‐Brandl, Annette

doi:10.1107/s1600536806020575

Cited by 7 publications

(5 citation statements)

References 3 publications

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“…This result is consistent with the reported structures of racemic and nonracemic crystalline ibuprofen in which the molecules form hydrogen-bonded cyclic dimers. 37,53,54 Moreover, these cyclic structures are found to be extremely stable compared to the linear ones. Indeed, the survival probability of the intermolecular HBs structures formed between the different ibuprofen molecules has been estimated from the time decay of the intermittent correlation function C n (t) ) 〈h n (t) • h n (0)〉 where h n (t) is unity if a given multimer composed of n molecules formed at time 0 remains intact at time tseven if it has broken in betweensand is zero otherwise.…”

Section: Resultsmentioning

confidence: 98%

“…This result is consistent with the estimation of a weak dipole moment from the ab initio calculations 40 of the isolated racemic (0.00 D) and nonracemic (0.54 D) cyclic dimers as found in crystalline ibuprofen. 37,53,54 However, the values of the dipole moment of the cyclic dimers obtained in the disordered phase (50:50 mixture of racemic/ nonracemic) are significantly higher than that for crystalline one since the structures might have distorted geometries.…”

Section: Table 2: Estimated Parameters Of the Arrhenius Fit τ(T) ) τ ...mentioning

confidence: 96%

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Molecular Motions in Amorphous Ibuprofen As Studied by Broadband Dielectric Spectroscopy

et al. 2008

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The molecular mobility of amorphous ibuprofen has been investigated by broadband dielectric relaxation spectroscopy (DRS) covering a temperature range of more than 200 K. Four different relaxation processes, labeled as alpha, beta, gamma, and D, were detected and characterized, and a complete relaxation map was given for the first time. The gamma-process has activation energy E a = 31 kJ.mol (-1), typical for local mobility. The weak beta-relaxation, observed in the glassy state as well as in the supercooled state was identified as the genuine Johari-Goldstein process. The temperature dependence of the relaxation time of the alpha-process (dynamic glass transition) does not obey a single VFTH law. Instead two VFTH regimes are observed separated by a crossover temperature, T B = 265 K. From the low temperature VFTH regime, a T g (diel) (tau =100 s) = 226 K was estimated, and a fragility or steepness index m = 93, was calculated showing that ibuprofen is a fragile glass former. The D-process has a Debye-like relaxation function but the temperature dependence of relaxation time also follows the VFTH behavior, with a Vogel temperature and a pre-exponential factor which seem to indicate that its dynamics is governed by the alpha-process. It has similar features as the Debye-type process observed in a variety of associating liquids, related to hydrogen bonding dynamics. The strong tendency of ibuprofen to form hydrogen bonded aggregates such as dimers and trimers either cyclic or linear which seems to control in particular the molecular mobility of ibuprofen was confirmed by IR spectroscopy, electrospray ionization mass spectrometry, and MD simulations.

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Section: Resultsmentioning

confidence: 98%

Section: Table 2: Estimated Parameters Of the Arrhenius Fit τ(T) ) τ ...mentioning

confidence: 96%

Molecular Motions in Amorphous Ibuprofen As Studied by Broadband Dielectric Spectroscopy

et al. 2008

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“…The chiral behavior of the ibuprofen free acid has been the subject of numerous studies, − and it has been reported that the racemic compound or “true racemate” (“any homogeneous solid composed of equimolar amounts of enantiomeric molecules”, following the IUPAC rule) is much more stable than the corresponding racemic conglomerate (or racemic mixture, that is, “a mixture of equimolar amounts of enantiomeric molecules present as separate solid phases”, following the IUPAC rule). In particular, the true racemate form is the only stable solid form, and, as a consequence, ( R , S )-ibuprofen has a dimorphic (true racemate/conglomerate) behavior of the monotropic type …”

Section: Introductionmentioning

confidence: 99%

Solid–Solid Transition between Hydrated Racemic Compound and Anhydrous Conglomerate in Na-Ibuprofen: A Combined X-ray Diffraction, Solid-State NMR, Calorimetric, and Computational Study

Rossi

Macedi

Paoli

et al. 2014

Crystal Growth & Design

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A combined X-ray diffraction (XRD), solid state nuclear magnetic resonance (SSNMR), differential scanning calorimetry (DSC), and modeling approach has been applied to study the solid−solid transition of ibuprofen sodium salt between the hydrated racemic compound (RS-H) and the anhydrous conglomerate (RS-A). For comparison, the dihydrate → anhydrous transformation of the sodium salt of the pure S-enantiomer of ibuprofen was also investigated by means of SSNMR and DSC. All the solid state studies indicate that the RS-H → RS-A transition is fully reversible under different experimental conditions [temperature, pressure (ambient and vacuum), and type of atmosphere (N 2 , air, and static dry by P 2 O 5 )]. The static and dynamic disorder affecting the isobutyl fragment in RS-H, already observed by SSNMR, has been further investigated by single crystal XRD and computational techniques. On these grounds, a model for the dihydrate → anhydrous solid−solid transformations is proposed.

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“…A sodium salt of a well-known racemic active pharmaceutical ingredient (API), (R,S)-(()-ibuprofen ((R,S)-(()-2-(4-isobutylphenyl)propionic acid) was chosen as a model system because of its parent acid (R,S)-(()-ibuprofen's worldwide commercial values in analgesic, anti-inflammatory, and antipyretic therapy 20 and (2) its abundant information in the literature. [21][22][23][24][25][26][27][28][29][30][31][32][33] It is known that (S)-(+)-ibuprofen is the active agent and (R)-(-)-ibuprofen is partially converted into (S)-(+)-ibuprofen in humans. Therefore, ibuprofen is marketed as a racemic compound.…”

Section: Introductionmentioning

confidence: 99%

Effects of Homochiral Molecules of (S)-(+)-Ibuprofen and (S)-(−)-Sodium Ibuprofen Dihydrate on the Crystallization Kinetics of Racemic (R,S)-(±)-Sodium Ibuprofen Dihydrate

Lee

Chen

Wang

2007

Crystal Growth & Design

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The aim of this paper is to identify the effects of homochiral molecules such as (S)-(+)-ibuprofen and (S)-(−)-sodium ibuprofen dihydrate on the crystallization kinetics: the induction period, the crystal growth rate, and the end point of the racemic compound of (R,S)-(±)-sodium ibuprofen dihydrate. Crystallization kinetics of racemic species of sodium ibuprofen dihydrate in the presence of small amounts of homochiral parent molecules of (S)-(+)-ibuprofen and its constituent enantiomers (S)-(−)-sodium ibuprofen dihydrate were studied by electrical conductance, optical microscopy, differential scanning calorimetry, and wide-angle powder X-ray diffraction. Racemic (R,S)-(±)-sodium ibuprofen dihydrate with self-association property was sensitive to processing history and deserved a tight control for reproducibility on scale-up. Crystals grown from a racemic water−acetone solution of sodium ibuprofen dihydrate and vaccuum-dried at 90 °C for 4 h produced racemic species of α-form racemic compounds and γ-form racemic conglomerates having a R:S w/w ratio of about 45:55 (enantiomeric excess of the solids, ee = 10% in S) by the addition of no additives, and 0.02 g of (S)-(+)-ibuprofen or 0.02 g of (S)-(−)-sodium ibuprofen, respectively. Fundamental parameters of the crystallization kinetics of racemic species of sodium ibuprofen dihydrate such as the induction time, τ; the interfacial energy, γ; the Gibbs energetic barrier, ΔG cr; the nucleation rate, J; the critical size of stable nuclei, rc ; the crystal mass growth rate, R G; the power number, g; and the end point were evaluated with different initial supersaturation ratios, S 0, and compared. In general, τ, ΔG cr, and r c decreased and J increased when S 0 increased or homochiral additives were added. γ decreased in the presence of homochiral additives. R G increased as S 0 increased in the presence of (S)-(+)-ibuprofen. g ranged from 0.5 to 1.7. The end point decreased in the presence of additives or with the increase in S 0. At high S 0, the effects of homochiral additives on the induction period, the crystal growth rate and the end point became to diminish. Adoption of such inexpensive, simple, and robust methods as electrical conductance, optical microscopy, and differential scanning calorimetry in common research laboratories offers the opportunity to the pharmaceutical industry to lower manufacturing cycle times and end product variability in a crystallization process that would result in shorter time to market and a reduced likelihood of drug product failures. The addition of configurationally similar homochiral molecules such as the parent acid or the same constituent enantiomer to the racemic solution may have opened a new doorway for the generation of racemic species that cannot be obtained by the addition of other impurities.

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Redetermination and H-atom refinement of (S)-(+)-ibuprofen. Corrigendum.

Abstract: Key indicatorsSingle-crystal X-ray study T = 298 K Mean (C-C) = 0.005 Å R factor = 0.038 wR factor = 0.104 Data-to-parameter ratio = 7.0 For details of how these key indicators were automatically derived from the article, see

Cited by 7 publications

References 3 publications

Molecular Motions in Amorphous Ibuprofen As Studied by Broadband Dielectric Spectroscopy

Molecular Motions in Amorphous Ibuprofen As Studied by Broadband Dielectric Spectroscopy

Solid–Solid Transition between Hydrated Racemic Compound and Anhydrous Conglomerate in Na-Ibuprofen: A Combined X-ray Diffraction, Solid-State NMR, Calorimetric, and Computational Study

Effects of Homochiral Molecules of (S)-(+)-Ibuprofen and (S)-(−)-Sodium Ibuprofen Dihydrate on the Crystallization Kinetics of Racemic (R,S)-(±)-Sodium Ibuprofen Dihydrate

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