Use of in situ FT-Raman spectroscopy to study the kinetics of the transformation of carbamazepine polymorphs

O’Brien, Laura E.; Timmins, Peter; Williams, Adrian C.; York, Peter

doi:10.1016/j.jpba.2004.06.024

Cited by 80 publications

(63 citation statements)

References 26 publications

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“…Combining both the XRPD and DSC results, it is reasonable to infer that more than one CBZ crystalline forms coexisted in the treated samples with the predominant polymorph being Form III. Such co-existence of different CBZ crystalline forms after SAS CO 2 treatment is very much in agreement with previous reports (20,26,28). The recrystallisation process prevents direct measurement of the enthalpy and quantification of low levels of different forms, especially the higher melting Form I in mixtures of the CBZ crystals is not possible (24).…”

Section: Differential Scanning Calorimetrysupporting

confidence: 93%

“…According to the literature, CBZ is known to have at least four anhydrous polymorphic forms: triclinic form (Form I), trigonal form (Form II), monoclinic form (Form III), and C-centered monoclinic form (Form IV) (21,23,25). O'Brien et al gave a detailed analysis of the four anhydrate polymorphic forms (26). Figure 3 (untreated), represents the XRPD pattern of untreated CBZ.…”

Section: Sas Co 2 System Operation Proceduresmentioning

confidence: 99%

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Self-built Supercritical CO2 Anti-solvent Unit Design, Construction and Operation using Carbamazepine

et al. 2008

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Abstract. The purpose of this study was to design and build a supercritical CO 2 anti-solvent (SAS) unit and use it to produce microparticles of the class II drug carbamazepine. The operation conditions of the constructed unit affected the carbamazepine yield. Optimal conditions were: organic solution flow rate of 0.15 mL/min, CO 2 flow rate of 7.5 mL/min, pressure of 4,200 psi, over 3,000 s and at 33°C. The drug solidstate characteristics, morphology and size distribution were examined before and after processing using X-ray powder diffraction and differential scanning calorimetry, scanning electron microscopy and laser diffraction particle size analysis, respectively. The in vitro dissolution of the treated particles was investigated and compared to that of untreated particles. Results revealed a change in the crystalline structure of carbamazepine with different polymorphs co-existing under various operation conditions. Scanning electron micrographs showed a change in the crystalline habit from the prismatic into bundled whiskers, fibers and filaments. The volume weighted diameter was reduced from 209 to 29 μm. Furthermore, the SAS CO 2 process yielded particles with significantly improved in vitro dissolution. Further research is needed to optimize the operation conditions of the self-built unit to maximize the production yield and produce a uniform polymorphic form of carbamazepine.

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Section: Differential Scanning Calorimetrysupporting

confidence: 93%

Section: Sas Co 2 System Operation Proceduresmentioning

confidence: 99%

Self-built Supercritical CO2 Anti-solvent Unit Design, Construction and Operation using Carbamazepine

et al. 2008

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“…In-situ Raman spectroscopy Carbamazepine [93] Solid-gas-solid polymorphic transformation of carbamazepine form III to form I Isothermal conversion monitored in an environmental chamber…”

Section: Crystallisation Experimentsmentioning

confidence: 99%

Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

et al. 2009

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Objectives Solid-state transformations may occur during any stage of pharmaceutical processing and upon storage of a solid dosage form. Early detection and quantification of these transformations during the manufacture of solid dosage forms is important since the physical form of an active pharmaceutical ingredient can significantly influence its processing behaviour, including powder flow and compressibility, and biopharmaceutical properties such as solubility, dissolution rate and bioavailability. Key findings Vibrational spectroscopic techniques such as infrared, near-infrared, Raman and, most recently, terahertz pulsed spectroscopy have become popular for solidstate analysis since they are fast and non-destructive and allow solid-state changes to be probed at the molecular level. In particular, Raman and near-infrared spectroscopy, which require no sample preparation, are now commonly used coupled to fibreoptic probes and are able to characterise solid-state conversions in-line. Traditionally, uni-or bivariate approaches have been used to analyse spectroscopic data sets; however, recently the simultaneous detection of several solid-state forms has been increasingly performed using multivariate approaches where even overlapping spectral bands can be analysed. Summary This review discusses the applications of different vibrational spectroscopic techniques to detect and monitor solid-state transformations possible for crystalline polymorphs, hydrates and amorphous forms of pharmaceutical compounds. In this context, the theoretical basis of solid-state transformations and vibrational spectroscopy and common experimental approaches are described, including recent methods of data analysis.

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“…8 Since the FT-Raman and micro-Raman techniques have begun to be used in the study of pharmaceutics only recently, a limited number of studies currently exist in the literature. [28][29][30][31][32][33][34] Before now, mapping has been used in only 1 study of solid dispersion systems. 22 The preparation and storage conditions of the solid dispersions play a critical role, as changes may alter the dissolution characteristics of the active ingredients over time.…”

Section: Characterization Of Solid Dispersionsmentioning

confidence: 99%

Characterization of the distribution, polymorphism, and stability of nimodipine in its solid dispersions in polyethylene glycol by micro-Raman spectroscopy and powder x-ray diffraction

Docoslis

Huszarik

Papageorgiou

et al. 2007

AAPS J

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In the present study, a series of solid dispersions of the drug nimodipine using polyethylene glycol as carrier were prepared following the hot-melt method. Micro-Raman spectroscopy in conjunction with X-ray powder diffractometry was used for the characterization of the solid structure, including spatial distribution, physical state, and presence of polymorphs, as well as storage stability of nimodipine in its solid formulations. The effect of storage time on drug stability was investigated by examination of the samples 6 months and 18 months after preparation. Confocal microRaman mapping performed on the samples showed that the drug was not uniformly distributed on a microscopic level. The presence of crystals of nimodipine with sizes varying between one and several micrometers was detected, and the crystal size seemed to increase with overall drug content. In samples examined 6 months after preparation it was found that the crystals existed mainly as the racemic compound, whereas after 18 months of storage mainly crystal conglomerates were observed.

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Use of in situ FT-Raman spectroscopy to study the kinetics of the transformation of carbamazepine polymorphs

Cited by 80 publications

References 26 publications

Self-built Supercritical CO2 Anti-solvent Unit Design, Construction and Operation using Carbamazepine

Self-built Supercritical CO2 Anti-solvent Unit Design, Construction and Operation using Carbamazepine

Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

Characterization of the distribution, polymorphism, and stability of nimodipine in its solid dispersions in polyethylene glycol by micro-Raman spectroscopy and powder x-ray diffraction

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