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J Pharm Pharmacol. 2009 Aug;61(8):971-88. doi: 10.1211/jpp/61.08.0001.

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

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School of Pharmacy, University of Otago, New Zealand.



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.


Vibrational spectroscopic techniques such as infrared, near-infrared, Raman and, most recently, terahertz pulsed spectroscopy have become popular for solid-state 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.


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.

[Indexed for MEDLINE]

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