Crystal face identification by Raman microscopy for assessment of crystal habit of a drug

Visualization of Primary Particles in a Tablet Based on Raman Crystal Orientation Mapping

“…Using an antiepileptic agent, phenytoin, as a model API, we have revealed that the peak area of the Raman spectrum changes depending upon the angle of the crystallographic axes and polarization direction of the excitation laser [10]. In our report, we showed that the crystal face of the API can be identified according to the combination of Raman spectra where the polarization direction was horizontal and vertical to the morphological long axis of a target face.…”

“…The structural data have been deposited with The Cambridge Crystallographic Data Centre (CCDC: 1433396). Being different from the structure of the phenytoin crystal [10], the unit cell of metformin hydrochloride was not a rectangular solid and was settled with a tilt against morphologically xyz axes ( Figure 1D). Thus, it was necessary to perform matrix calculations to resolve the abc component as shown in Materials and Method.…”

Vapor Phase Alkyne Coating of Pharmaceutical Excipients: Discrimination Enhancement of Raman Chemical Imaging for Tablets

“…The structure of the coating component in the vapor phase reaction of propargyl bromide and triethylamine was determined as triethylpropargylammonium bromide (Scheme 1) by NMR and MS after the overnight exposure of silica gel to this combination and the elution of the coating component by dimethylsulfoxide. 1 13 C HMBC) were also carried out to support this structure (Supporting Information, pages S1-S5). A nucleophilic attack of triethylamine on the propargyl halide in the vapor phase resulted in the formation of a quaternary ammonium salt, and this compound adhered on the surface of silica gel (Scheme 1).…”

“…Of these methods, Raman chemical imaging appears to be superior in many aspects. The advantages of Raman imaging are that the Raman spectrum usually consists of clear signals, which help to discriminate not only the chemical structure, but also the crystal form or crystal face, of APIs, and that high‐resolution images can be obtained at a single‐micrometer resolution. There have been many reports regarding the use of Raman imaging to analyze particle size and the dispersion of APIs in tablet cross‐sections …”

Kinetics Study of Cocrystal Formation Between Indomethacin and Saccharin Using High-Shear Granulation With In Situ Raman Spectroscopy

“…33 Many authors used Raman to selectively distinguish between the crystal structures of an API. 34,35 The obtained multivariable spectra data during pharmaceutical processes are required for quantitative analysis using chemometrics, for instance, multivariate curve resolution (MCR), 36,37 partial least squares regression, 38 or 2-dimensional correlation spectroscopy. 39 The reasons why chemometrics has been used are for noise reduction, prevention of multicollinearity, characterization, and statistical control.…”