Collective relaxation dynamics and crystallization kinetics of the amorphous Biclotymol antiseptic

Abstract

We employ dielectric spectroscopy to monitor the relaxation dynamics and crystallization kinetics of the Biclotymol antiseptic in its amorphous phase. The glass transition temperature of the material as determined by dielectric spectroscopy is T g = 290±1 K. The primary (α) relaxation dynamics is observed to follow a Vogel-Fulcher-Tammann temperature dependence, with a kinetic fragility index m = 86±13, which classifies Biclotymol as a relatively fragile glass former. A secondary relaxation is also observed, corresponding to an intramolecular dynamic process of the non-rigid Biclotymol molecule. The crystallization kinetics, measured at four different temperatures above the glass transition temperature, follows an Avrami behavior with exponent virtually equal to n = 2, indicating one-dimensional crystallization into needle-like crystallites, as experimentally observed, with a time-constant nucleation rate. The activation barrier for crystallization is found to be E a = 115±22 kJ mol -1 .

Monitoring the recrystallisation of amorphous xylitol using Raman spectroscopy and wide-angle X-ray scattering

“…y is the amount of crystalline substance, k describes the rate of conversion, t is time, t is the lag time before onset of crystallization and n describes the dimensionality of crystal growth (Tripathi et al, 2015;Çelikbilek et al, 2012). As the crystallization curves showed signs of a two-phased growth mechanism, only the initial phase of rapid growth was investigated.…”

Transformation of an active pharmaceutical ingredient upon high-energy milling: A process-induced disorder in Biclotymol

“…More recently, a metastable crystalline form has been highlighted through thermal analyses starting from amorphous Biclotymol and the relative stability of these two polymorphs as a function of pressure and temperature was reported (Ceolin et al, 2008). Moreover, a recent study (Tripathi et al, 2015) employed employ broadband dielectric spectroscopy to monitor relaxation dynamics of Biclotymol in its amorphous phase. Biclotymol exhibits a glass transition temperature at T g = 20°C which gives the opportunity to perform high-energy milling operations above and below T g .…”

Enhancement of the Physical and Chemical Stability of Amorphous Drug–Polymer Mixtures via Cryogenic Comilling

“…The relaxation visible at high frequency in the spectra at lower temperature (panel (a)) matches the spectral position of the secondary relaxation (s b , where the subscript "b" stands for Biclotymol) reported in the pure drug. 19 We observed that the intensity of this feature was higher the larger the Biclotymol content in the mixture. Only this drug-related relaxation was observed in the isothermal spectra at low temperature, while no water-related signal was detected (both the w 1 and w 2 relaxations were absent).…”

“…The fact that this relaxation is observed in the mixtures but not in pure PVP might be partially due to the fact that the Biclotymol molecules act as dipolar "markers" runs, despite the fact that the samples were heated up to 455 K, that is, more than 100 K higher than the onset of the recrystallization process of pure supercooled Biclotymol. 19 While the structural relaxation time and thus the viscosity of the sample decrease significantly with increasing Biclotymol content, the γ relaxation time appears to be only slightly affected by this change in the macroscopic properties of the mixture and by the enhancement of the cooperative segmental motions (see Figure 5). This entails that the frequency separation between the α and γ decreases with increasing drug loading.…”

“…A VFT behavior is typical of cooperative structural relaxations in glass forming systems, and it is obeyed for example by the structural relaxation of pure supercooled Biclotymol. 19 The non- �. The dielectric T g values, listed in Table 1, are in agreement with the calorimetric glass transition temperatures, and both shift to lower values with increasing drug content.…”