Polymorph Discrimination Using Low Wavenumber Raman Spectroscopy

Roy, Saikat; Chamberlin, Brianna L.; Matzger, Adam J.

doi:10.1021/op400102e

Cited by 62 publications

(59 citation statements)

References 28 publications

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“…Additionally, we focus on correlations within the 0-900cm −1 region only. The fol- [44] and [54]. The shaded areas around the anharmonic spectra indicate the uncertainty derived from the statistical error of the different trajectories.…”

Section: Mode Couplingmentioning

confidence: 99%

Anharmonic effects in the low-frequency vibrational modes of aspirin and paracetamol crystals

Raimbault

Athavale

Rossi

2019

Phys. Rev. Materials

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The low-frequency range of vibrational spectra is sensitive to collective vibrations of the lattice. In molecular crystals, it can be decisive to identify the structure of different polymorphs, and in addition, it plays an important role on the magnitude of the temperature-dependent component of vibrational free energy differences between these crystals. In this work we study the vibrational Raman spectra and vibrational density of states of different polymorphs of the flexible Aspirin and Paracetamol crystals based on dispersion-corrected density-functional theory, density-functional perturbation theory, and ab initio molecular dynamics. We examine the effect of quasi-harmonic lattice expansion and compare the results of harmonic theory and the time correlation formalism for vibrational spectra. Lattice expansion strongly affects the collective vibrations below 300 cm −1 , but it is significantly less important at higher frequencies, while thermal nuclear motion can be important in the full vibrational range. We also observe that the inclusion or neglect of many-body van der Waals dispersion interactions do not cause large differences in the low-frequency range of Raman spectra or vibrational density of states, provided the lattice constants are fixed. We obtain quantitative agreement with experimental room-temperature Raman spectra below 300 cm −1 for all polymorphs studied. Examining the two-dimensional correlations between different vibrations, we find which modes show a larger degree of anharmonic coupling to others, providing a possible route to assess the accuracy of harmonic free energy evaluations in different cases.

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Section: Mode Couplingmentioning

confidence: 99%

Anharmonic effects in the low-frequency vibrational modes of aspirin and paracetamol crystals

Raimbault

Athavale

Rossi

2019

Phys. Rev. Materials

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“…Matzger's group compared the utility of LFRS and conventional Raman spectroscopy for the discrimination of the different phases of ten polymorphic pharmaceuticals including the widely studied model polymorphic API paracetamol [69]. The discriminating power of the LF range was found to be clearly superior to that of the conventional Raman range and to present a fingerprint region for polymorphs.…”

Section: Low-frequency Raman Spectroscopymentioning

confidence: 99%

“…On the other hand, in the case of carbamazepine two of the five known polymorphs, form I and II, have very similar lattice structures and this is reflected in the similarity of their LF Raman spectra. Matzger and coworkers suggested that the LF range could be used to assess packing similarities in the absence of crystallographic data [69]. Very often the combined analysis of the phonon and intramolecular vibrations prove to provide useful complementary information on phase transformations.…”

Section: Low-frequency Raman Spectroscopymentioning

confidence: 99%

Application of Vibrational Spectroscopy to Study Solid-state Transformations of Pharmaceuticals

Erxleben

2016

CPD

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Understanding the properties, stability and transformations of the solid-state forms of an active pharmaceutical ingredient (API) in the development pipeline is of crucial importance for process-development, formulation development and FDA approval. Investigation of the polymorphism and polymorphic stability is a routine part of the preformulation studies. Vibrational spectroscopy allows the real-time in situ monitoring of phase transformations and probes intermolecular interactions between API molecules, between API and polymer in amorphous solid dispersions or between API and coformer in cocrystals or coamorphous systems and thus plays a major role in efforts to gain a predictive understanding of the relative stability of solid-state forms and formulations. Infrared (IR), near-infrared (NIR) and Raman spectroscopies, alone or in combination with other analytical methods, are important tools for studying transformations between different crystalline forms, between the crystalline and amorphous form, between hydrate and anhydrous form and for investigating solid-state cocrystal formation. The development of simple-to-use and cost-effective instruments on the one hand and recent technological advances such as access to the low-frequency Raman range down to 5 cm-1, on the other, have led to an exponential growth of the literature in the field. This review discusses the application of IR, NIR and Raman spectroscopies in the study of solid-state transformations with a focus on the literature published over the last eight years.

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“…Based on this notion, low wavenumber Raman spectroscopy and terahertz (THz) spectroscopy has been used for polymorphs discrimination. [13][14][15] Much less work has been conducted in pharmaceuticals with infrared spectroscopy in this low wavenumber region, in spite of the fact that FT-IR is the most common of all vibrational spectroscopies. This apparent paradox can be traced to the typical configuration of mid-IR spectrophotometers which are equipped with window materials that absorb far-IR radiation.…”

Section: Introductionmentioning

confidence: 99%

Far-Infrared Spectroscopy as a Probe for Polymorph Discrimination

Suresh

Ashe

Matzger

2019

Journal of Pharmaceutical Sciences

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Pharmaceutical crystalline polymorph and amorphous form detection and quantification is a standard requirement in the pharmaceutical industry. Infrared (IR) spectroscopy provides an important probe for the characterization of polymorphs. Nonetheless, characterization and discrimination among polymorphs using mid-IR spectroscopy is not always possible in part because the technique mainly probes vibrational modes arising from functional groups in the sample. In the present work, far-infrared (far-IR) spectroscopy is demonstrated for the discrimination of polymorphs. This region is influenced by delocalized lattice vibrational modes derived from intermolecular forces and packing arrangements in the crystal structure. A total of ten polymorphic pharmaceuticals were prepared to conduct a critical evaluation of the question does this far-IR region add value for polymorph differentiation? It is demonstrated that the far-IR region offers high discriminating power for polymorphs compared to the mid-infrared spectral region. In addition, structural similarity and dissimilarity in polymorphic packing arrangements can be derived from this analysis.

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Polymorph Discrimination Using Low Wavenumber Raman Spectroscopy

Cited by 62 publications

References 28 publications

Anharmonic effects in the low-frequency vibrational modes of aspirin and paracetamol crystals

Anharmonic effects in the low-frequency vibrational modes of aspirin and paracetamol crystals

Application of Vibrational Spectroscopy to Study Solid-state Transformations of Pharmaceuticals

Far-Infrared Spectroscopy as a Probe for Polymorph Discrimination

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