Article

Relaxation and crystallization of amorphous carbamazepine studied by terahertz pulsed spectroscopy

School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand.
Journal of Pharmaceutical Sciences (Impact Factor: 3.01). 10/2007; 96(10):2703-9. DOI: 10.1002/jps.20908
Source: PubMed

ABSTRACT At the example of carbamazepine the crystallization of a small organic molecule from its amorphous phase was studied using in situ variable temperature terahertz pulsed spectroscopy (TPS). Even though terahertz spectra of disordered materials in the glassy state exhibit no distinct spectral features we demonstrate subtle changes in the spectra with increasing temperature and discuss the findings in respect to the density of vibrational states. The crystallization leads to distinct spectral features allowing the crystallization and subsequent polymorphic phase transition at higher temperatures to be studied in detail. It is possible to study both relaxation and crystallization processes by variable temperature TPS.

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Available from: J. Axel Zeitler, Apr 29, 2014
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    • "diation . Thus , they cause no or little interference when investigating crystalline drugs . Recently , amorphous material was characterised using TPS while heating the sample . Structural relaxation and increase in molecular mobility for the amorphous sample were visible in the absorbance spectra when transforming to the glassy or rubbery state ( Zeitler et al . 2007c ) ."
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    ABSTRACT: In order to improve and continuously develop the quality of pharmaceutical products, the process analytical technology (PAT) framework has been adopted by the US Food and Drug Administration. One of the aims of PAT is to identify critical process parameters and their effect on the quality of the final product. Real time analysis of the process data enables better control of the processes to obtain a high quality product. The main purpose of this work was to monitor crucial pharmaceutical unit operations (from blending to coating) and to examine the effect of processing on solid-state transformations and physical properties. The tools used were near-infrared (NIR) and Raman spectroscopy combined with multivariate data analysis, as well as X-ray powder diffraction (XRPD) and terahertz pulsed imaging (TPI). To detect process-induced transformations in active pharmaceutical ingredients (APIs), samples were taken after blending, granulation, extrusion, spheronisation, and drying. These samples were monitored by XRPD, Raman, and NIR spectroscopy showing hydrate formation in the case of theophylline and nitrofurantoin. For erythromycin dihydrate formation of the isomorphic dehydrate was critical. Thus, the main focus was on the drying process. NIR spectroscopy was applied in-line during a fluid-bed drying process. Multivariate data analysis (principal component analysis) enabled detection of the dehydrate formation at temperatures above 45°C. Furthermore, a small-scale rotating plate device was tested to provide an insight into film coating. The process was monitored using NIR spectroscopy. A calibration model, using partial least squares regression, was set up and applied to data obtained by in-line NIR measurements of a coating drum process. The predicted coating thickness agreed with the measured coating thickness. For investigating the quality of film coatings TPI was used to create a 3-D image of a coated tablet. With this technique it was possible to determine coating layer thickness, distribution, reproducibility, and uniformity. In addition, it was possible to localise defects of either the coating or the tablet. It can be concluded from this work that the applied techniques increased the understanding of physico-chemical properties of drugs and drug products during and after processing. They additionally provided useful information to improve and verify the quality of pharmaceutical dosage forms
    Division of Pharmaceutical Technology, University of Helsinki, 08/2008, Degree: PhD Pharm, Supervisor: Jouko Yliruusi
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    • "diation . Thus , they cause no or little interference when investigating crystalline drugs . Recently , amorphous material was characterised using TPS while heating the sample . Structural relaxation and increase in molecular mobility for the amorphous sample were visible in the absorbance spectra when transforming to the glassy or rubbery state ( Zeitler et al . 2007c ) ."
    [Show abstract] [Hide abstract]
    ABSTRACT: In order to improve and continuously develop the quality of pharmaceutical products, the process analytical technology (PAT) framework has been adopted by the US Food and Drug Administration. One of the aims of PAT is to identify critical process parameters and their effect on the quality of the final product. Real time analysis of the process data enables better control of the processes to obtain a high quality product. The main purpose of this work was to monitor crucial pharmaceutical unit operations (from blending to coating) and to examine the effect of processing on solid-state transformations and physical properties. The tools used were near-infrared (NIR) and Raman spectroscopy combined with multivariate data analysis, as well as X-ray powder diffraction (XRPD) and terahertz pulsed imaging (TPI). To detect process-induced transformations in active pharmaceutical ingredients (APIs), samples were taken after blending, granulation, extrusion, spheronisation, and drying. These samples were monitored by XRPD, Raman, and NIR spectroscopy showing hydrate formation in the case of theophylline and nitrofurantoin. For erythromycin dihydrate formation of the isomorphic dehydrate was critical. Thus, the main focus was on the drying process. NIR spectroscopy was applied in-line during a fluid-bed drying process. Multivariate data analysis (principal component analysis) enabled detection of the dehydrate formation at temperatures above 45°C. Furthermore, a small-scale rotating plate device was tested to provide an insight into film coating. The process was monitored using NIR spectroscopy. A calibration model, using partial least squares regression, was set up and applied to data obtained by in-line NIR measurements of a coating drum process. The predicted coating thickness agreed with the measured coating thickness. For investigating the quality of film coatings TPI was used to create a 3-D image of a coated tablet. With this technique it was possible to determine coating layer thickness, distribution, reproducibility, and uniformity. In addition, it was possible to localise defects of either the coating or the tablet. It can be concluded from this work that the applied techniques increased the understanding of physico-chemical properties of drugs and drug products during and after processing. They additionally provided useful information to improve and verify the quality of pharmaceutical dosage forms Lääketeollisuudessa on tänä päivänä yhä kasvava kiinnostus siirtää laadunvarmistuksen painopistettä lopputuotteiden analysoinnista eri valmistusvaiheiden aikaiseen testaukseen. Tästä johtuen tässä työssä käytettiin erilaisia menetelmiä lääkevalmistuksen prosessivaiheiden kuten lääkeaineen ja apuaineen sekoittamisen, kostearakeistuksen, rakeiden kuivaamisen, tablettien puristamisen sekä päällystyksen tutkimiseen. Tutkimuksessa käytetyt prosessianalyysitekniikat olivat pääasiallisesti spektroskooppisia tekniikoita kuten lähialueen infrapunaspektroskopia. Näitä tekniikoita sovellettiin esimerkiksi lääkeaineen kiderakenteessa tapahtuvien muutosten selvittämiseen sekä tablettien kalvopäällysteen muodostumisen seuraamiseen päällystyksen aikana. Lisäksi käytettiin kalvopäällysteen laadunvarmistukseen uutta terahertsiteknologiaan perustuvaa kuvantamismenetelmää, joka mahdollistaa lääketablettien tutkimisen niitä vaurioittamatta.
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