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Acta Pharmaceutica, Vol. 64 No. 1, 2014.

Original scientific paper

https://doi.org/10.2478/acph-2014-0009

Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

TOMISLAV JEDNAČAK ; Department of Chemistry, Faculty of Natural Science, University of Zagreb, HR-10000 Zagreb, Croatia
ADEN HODZIC ; Research Center Pharmaceutical Engineering GmbH, A-8010 Graz, Austria
OTTO SCHEIBELHOFER ; Research Center Pharmaceutical Engineering GmbH, A-8010 Graz, Austria
MARIJAN MARIJAN ; Department of Chemistry, Faculty of Natural Science, University of Zagreb, HR-10000 Zagreb, Croatia
JOHANNES G. KHINAST ; Research Center Pharmaceutical Engineering GmbH, A-8010 Graz, Austria; Institute for Particle and Process Technology, A-8010 Graz, Austria
PREDRAG NOVAK ; Department of Chemistry, Faculty of Natural Science, University of Zagreb, HR-10000 Zagreb, Croatia

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Abstract

Crystallization of the drug entacapone from binary solvent mixtures was monitored in situ using Raman optical probe. The recorded Raman spectra and statistical analysis, which included the principal components method and indirect hard modeling made it possible to estimate the starting point of crystallization, to assess crystallization temperatures and to provide information on the polymorphic content in the mixture. It was established that the crystallization temperatures were proportional to the volume content of the solvent in the mixtures. The samples were also evaluated off-line via Raman spectroscopy and SWAXS. The collected data showed the presence of forms β and γ in all solvent mixtures. In toluene/methanol 30:70 mixture, in addition to forms β and γ at least one of the forms A, D or α was also indicated by SWAXS. The results have shown that the presence of a particular polymorph is strongly dependent on the nature and portion of the solvent in the binary solvent mixture.

Keywords

entacapone; in-line crystallization monitoring; multivariate analysis; polymorphism; Raman spectroscopy; SWAXS

Hrčak ID:

113592

URI

https://hrcak.srce.hr/113592

Publication date:

31.3.2014.

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