Ordering and disordering of molecular solids upon mechanical milling: the case of fananserine.

In this article, we study the physical transformations of the forms III and IV of fananserine upon mechanical milling. The investigations have been performed through X-Ray powder diffraction and differential scanning calorimetry experiments. The results indicate that both forms undergo a polymorphic transformation toward the metastable form I upon milling at room temperature (25 degrees C) while an amorphization is observed upon milling at 0 degrees C. It thus appears that the nature of the transformation induced by milling does not depend on the initial polymorphic state, but strongly depends on the milling temperature. Interestingly, the change in the nature of the transformation with the milling temperature occurs in a short temperature range around the glass transition temperature (T(g) = 19 degrees C). The implication of T(g) in the duality "amorphisation/polymorphic transformation" generally observed upon milling is thus discussed. The physical stability of the end products is also investigated and discussed with respect to the storage temperature of the material.

Molecular mobility in glass forming fananserine: a dielectric, NMR, and TMDSC investigation.

PURPOSE: This study was conducted to characterize the molecular mobility of supercooled fananserine and derive from this analysis the non-Arrhenius and nonexponential properties of the primary alpha-relaxation. METHODS: The use of three investigation techniques of the molecular mobility, namely, dielectric relaxation, modulated differential scanning calorimetry, and proton nuclear magnetic resonance, allowed us to describe the dynamic properties of supercooled fananserine on a wide range of frequencies and temperatures, ranging from the melting temperature T(m) = 372 K down to the glass transition temperature T(g) = 292 K. RESULTS: We emphasized the capacity of these three techniques to give a coherent set of information. We used the coupling-model theory to interpret the dielectric results. It allowed us to identify two relaxation processes (alpha and beta), corresponding to different molecular motions. The temperature evolution of the alpha-relaxation indicates that fananserine is a fragile glass former, as reflected by the steepness index value, m = 77. The temperature T(o) where the relaxation times diverge was also determined. CONCLUSIONS: The description of the dielectric relaxation data in terms of the Kohlrausch-Williams-Watt relaxation function has shown the existence of an additional low-amplitude relaxation process assigned to the so-called Johari-Goldstein process. Mainly concerned by the primary alpha-process directly involved in the glass formation, we derived from this analysis the characteristic features of this process and showed that supercooled fananserine is characterized by a strongly non-Arrhenius and nonexponential behavior.

Solid state NMR and DSC methods for quantifying the amorphous content in solid dosage forms: an application to ball-milling of trehalose.

The purpose of this study was to determine quantitatively the amorphous fraction in crystalline-amorphous powder mixtures of trehalose, in order to assess the ability of the (13)C NMR technique for quantitative amorphous characterization. The NMR method is described in detail and its accuracy is compared to that of the DSC technique. Amorphous trehalose was prepared by mechanical milling. Samples with different amorphous fractions were prepared by physical mixing of purely amorphous and purely crystalline powders. The results reveal a close correlation between the imposed compositions of the physical mixtures and those determined by NMR and DSC, indicating that both are useful and accurate methods for compositional characterization of powders. The NMR method is then used to determine the evolution of the amorphous fraction in a trehalose powder, during a milling procedure which ultimately leads to a fully amorphous state.