Micro-Raman spectroscopy of caffeine polymorphs in tablets: comparison between low and high frequency investigations
S. Huberta, T. Manakula, D. De Lignyb, A. Hedouxc, Y. Guinetc, B. Champagnonb, S. Briancona, F. Puela
a Université de Lyon, F-69622 Lyon, France. Université Lyon 1, Villeurbanne, CNRS, UMR5007, Laboratoire d’Automatique et de Génie des Procédés (LAGEP), CPE-Lyon, 43 bd du 11
... [Show full abstract] Novembre 1918, 69100 Villeurbanne, France
b Université de Lyon, F-69622 Lyon, France. Université Lyon 1, Villeurbanne, CNRS, UMR5620, Laboratoire Physico-Chimie des Matériaux Luminescents (LPCML), 43 bd du 11 Novembre 1918, 69100 Villeurbanne, France
c Univ Lille Nord de France, F-59000 Lille, France. USTL, UMET, UMR 8207, F-59650 Villeneuve d’Ascq, France
During the compression process, API and excipients are stressed and it is not uncommon to observe phase transition during this manufacturing step1,2,3 and during the tablet storage4. Many parameters in the process itself could have an impact on the average transformation in final tablets like pressure, temperature and mechanical stress5. This work is focused on the method elaborated for probing caffeine polymorphs from Raman mapping of tablets carried out in internal and external mode regions.
Two quantitative methods for determining the degree of transition between caffeine polymorphs at the surface of tablets were set up, depending on the spectral domain analyzed.
The transition degree ρlow of Form I toward Form II estimated in the low frequency range is determined from integration between 32 and 76 cm-1 of the growing shoulder, distinctive of the emerging Form II. All analyzed areas are characterized by the presence of Form I of caffeine more or less transformed into Form II. No pure polymorphic Forms were detected in tablets. Given the data processing used in this method, only small areas of the surface tablet can be analyzed. As a consequence, the estimate of ρlow is not really representative of the average value of the transition degree in the whole tablet.
The mapping of pharmaceutical ingredients, micro-crystalline cellulose, magnesium stearate and caffeine was performed in the high frequency range, where internal modes are active, by fitting a characteristic peak position for each compound. In that case, the transition degree ρhigh was estimated as the area ratio between two peaks fitted in the asymmetric band in the 1327-1330 cm-1 range. Larger areas of tablets can be analyzed by this method, leading to an evaluation of the transition degree representative of the tablet surface and section. Micro-Raman spectroscopy at high frequency also revealed that caffeine Form I particles were partially transformed in all parts of the tablets at a microscopic scale.
The contribution of both methods, ρlow and ρhigh, will be discussed and their results compared.
References
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5 Morris, K.R., et al., 2001. Adv. Drug Deliv. Rev. 48, 91–114.