RAMAN SUPPLEMENT


there is no periodicity of atoms because of the orientational disorder, the crystalline lattice resulting only from the periodicity of the centers of mass. Form I is metastable below 153°C and its transformation toward the stable form II is hindered at room temperature. Despite more than 50 years of investigations, mainly by X-ray diffraction experiments, the structural description of the commercial form II remains unclear. The last few studies27,28 large unit cell (4454 Å3


report an unusual , Z = 20), inducing the


existence of a lot of Bragg peaks at small angles, not observed in the powder diffraction pattern. Raman spectroscopy gives the opportunity to bring out information on the molecular packing in form II. After I→II transformation at 90°C, the


FIGURE 6 Raman spectra of ground IMC recorded during isothermal aging at room temperature (20°C below Tg


)


a) In the low-frequency range b) In the C = O stretching region The arrows show the detection of the first traces of crystallisation in each region


MPa pressure range. In some cases, the application of such a pressurisation makes possible the transformation of a metastable form toward the stable crystalline form, as observed for caffeine22


. Form I of caffeine is


known as a highly disordered rotator phase23,24 characterised by slow rotation of molecules around the C3


contribution of librational motions25,26 molecular axis. As a consequence, the LFRS of form I is dominated by the and


characterised by a broad band, as shown in Figure 8, which mimics a density of librational states. No phonon peaks are detected, since


FIGURE 8 LFRS of forms I and II of caffeine; form II is obtained after isothermal aging at 90°C where the transformation is faster. The spectrum of form II is compared to that of theophylline in the inset


LFRS of form II is compared to that of form I. LFRS of form II can be distinguished from that of form I, by the presence of two bands, too broad to be considered as phonon peaks. This band shape of the LFRS indubitably reveals a high degree of disorder in form. The LFRS of form II of caffeine corresponds rigorously to the envelope of the phonon peaks of crystalline theophylline, belonging to the methyl xanthine family (see the inset of Figure 8). Consequently, form II of caffeine can be described from the molecular packing of theophylline with a persisting orientational disorder. By contrast to IMC, the identification of


FIGURE 7 Crystallisation kinetics at room temperature of ground IMC with and without PVP; the line corresponds to the fitting curve using an Avrami-like function


16


European Pharmaceutical Review Volume 16 | Issue 5 | 2011


the different phases is not possible in the molecular fingerprint region between 800 and


“Micro-structural information in solid dosage forms can also be obtained by


micro-Raman spectroscopy”


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