Thermal behavior and molecular mobility studies in the supercooled liquid and glassy states of carvedilol and loratadine.

The thermal behavior of carvedilol and loratadine was studied by differential scanning calorimetry (DSC). The glass-forming ability, as well as the the tendency for crystallization from the glass (glass stability) and from the metastable and equilibrium melt were also investigated by DSC. In addition this technique was also used to characterize the glass transition of carvedilol and loratadine by determining the activation energy of the structural relaxation, the dynamic fragility, and the heat capacity jump associated with the glass transformation. Different aspects of the molecular mobility in carvedilol and loratadine were analyzed by Thermally Stimulated Depolarization Currents (TSDC), while in carvedilol the Dielectric Relaxation Spectroscopy (DRS) technique was also used. Carvedilol stands out for its high values of specific heat jump and dynamic fragility, which has been attributed to the particular mobility of this glass-former in the glass transformation region, a consequence of specific characteristics of its molecular structure. These molecular features are also at the origin of a relaxation above Tg that has been detected and characterized by TSDC; the DRS investigation allowed to better understand the molecular dynamics in carvedilol in the amorphous solid, in the metastable liquid state and in the glass transformation region. Finally, the secondary relaxations in loratadine were studied by TSDC, while those in carvedilol were studied by the two dielectric techniques and the results were compared and discussed.

Thermal Behavior and Slow Relaxation Dynamics in Amorphous Efavirenz: A Study by DSC, XRPD, TSDC, and DRS.

The analysis of the thermal behavior of efavirenz showed a high glass-forming ability and good glass stability of this glass-forming liquid at room temperature. No polymorphic forms were formed either by cold crystallization or by recrystallization from solvent acetone. The determination of the dynamic fragility by the differential scanning calorimetry, thermally stimulated depolarization currents (TSDC), and dielectric relaxation spectroscopy (DRS) techniques is unanimous in suggesting efavirenz as a moderately fragile liquid. With DRS, secondary relaxations were detected, however, with weak intensities that did not allow the respective kinetic analysis; in contrast, TSDC allows clearly resolving the components of the secondary ß-relaxation below Tg, with activation energies distributed between about 75 and 90 kJ mol-1 and Arrhenius prefactors of the order of 10-13 s. In this regard, the TSDC technique proved to be more effective compared to DRS in characterizing the secondary relaxation. The glass forming ability and glass stability found for efavirenz have been discussed in terms of various thermodynamic and kinetic parameters such as the reduced glass transition temperature, Tgred, the dynamic fragility, m, the stretching exponent, ßKWW, the melting entropy, ΔSfus, and the molecular stiffness. The exceptionally low value of efavirenz fusion entropy was highlighted as a key feature of the thermal behavior of this glass-forming liquid.

The Slow Relaxation Dynamics in the Amorphous Pharmaceutical Drugs Cimetidine, Nizatidine, and Famotidine.

The slow molecular mobility in the amorphous solid state of 3 active pharmaceutical drugs (cimetidine, nizatidine, and famotidine) has been studied using differential scanning calorimetry and the 2 dielectric-related techniques of dielectric relaxation spectroscopy and thermally stimulated depolarization currents. The glass-forming ability, the glass stability, and the tendency for crystallization from the equilibrium melt were investigated by differential scanning calorimetry, which also provided the characterization of the main relaxation of the 3 glass formers. The chemical instability of famotidine at the melting temperature and above it prevented the preparation of the amorphous for dielectric studies. In contrast, for cimetidine and nizatidine, the dielectric study yielded the main kinetic features of the α relaxation and of the secondary relaxations. According to the obtained results, nizatidine displays the higher fragility index of the 3 studied glass-forming drugs. The thermally stimulated depolarization current technique has proved useful to identify the Johari-Goldstein relaxation and to measure τßJG in the amorphous solid state, that is, in a frequency range which is not easily accessible by dielectric relaxation spectroscopy.

A stable amorphous statin: solid-state NMR and dielectric studies on dynamic heterogeneity of simvastatin.

Statins have been widely used as cholesterol-lowering agents. However, low aqueous solubility of crystalline statins and, consequently, reduced biovailability require seeking for alternative forms and formulations to ensure an accurate therapeutic window. The objective of the present study was to evaluate the stability of amorphous simvastatin by probing molecular dynamics using two nondestructive techniques: solid-state NMR and dielectric relaxation spectroscopy. Glassy simvastatin was obtained by the melt quench technique. (13)C cross-polarization/magic-angle-spinning (CP/MAS) NMR spectra and (1)H MAS NMR spectra were obtained from 293 K up to 333 K (Tg ≈ 302 K). The (13)C spin-lattice relaxation times in the rotating frame, T1ρ, were measured as a function of temperature, and the correlation time and activation energy data obtained for local motions in different frequency scales revealed strong dynamic heterogeneity, which appears to be essential for the stability of the amorphous form of simvastatin. In addition, the (1)H MAS measurements presented evidence for mobility of the hydrogen atoms in hydroxyl groups which was assigned to noncooperative secondary relaxations. The complex dielectric permittivity of simvastatin was monitored in isochronal mode at five frequencies (from 0.1 to 1000 kHz), by carrying out a heating/cooling cycle allowing to obtain simvastatin in the supercooled and glassy states. The results showed that no dipolar moment was lost due to immobilization, thus confirming that no crystallization had taken place. Complementarily, the present study focused on the thermal stability of simvastatin using thermogravimetric analysis while the thermal events were followed up by differential scanning calorimetry and dielectric relaxation spectroscopy. Overall, the results confirm that the simvastatin in the glass form reveals a potential use in the solid phase formulation on the pharmaceutical industry.

Investigating the influence of morphology in the dynamical behavior of semicrystalline Triton X-100: insights in the detection/nondetection of the α'-process.

The paper investigates the influence of the crystalline structure in the dynamical behavior of semicrystalline Triton X-100 allowing enlightening the reason for the detection/nondetection of the α'-process. The work was preceded by the study of the full amorphous material for which dielectric relaxation spectroscopy (DRS) identified multiple relaxations: the α-process associated with the dynamical glass transition and two secondary relaxations (ß- and γ- processes). To evaluate how crystallinity affects the detected relaxation processes, different crystallizations were induced under high and low undercooling conditions. While the secondary relaxations are unaffected by crystallization, the mobility of the cooperative bulk α-process is sensitive to the distinct morphologies. The distinct semicrystalline states were structurally characterized by X-ray diffraction and polarized optical microscopy (POM). Differential scanning calorimetry (DSC) was used as a complementary tool. Depending on the extension of undercooling, large and well-defined shperulites or grainy-like structure emerge, respectively, for low and high undercooling degrees, as monitored by POM. In the two crystalline structures, X-ray diffraction patterns detected the amorphous halo meaning that both are semicrystalline. However, no differences between the amorphous regions are indentified by this technique; the distinction was done by means of dielectric measurements probing different mobilities in each of those regions. When the large spherulites evolve, the bulk-like α-process never goes to extinction and slightly shifts to low frequencies increasing the associated glass transition by 2-3 K, as confirmed by DSC; the slight change is an indication that the dimensions of the persisting amorphous regions become comparable to the length scale inherent to the cooperative motion that determines the glass transition in the full amorphous material. For the grainy-like structure, the α-process becomes extinct and an α'-process evolves as revealed by isochronal plots of dielectric measurements, with the features of a glass transition as confirmed by temperature modulated differential scanning calorimetry; both techniques indicate a 10-12 K displacement of the associated hindered glass transition toward higher temperatures relative to the amorphous glass transition. It is concluded that the detection of the α'-process in Triton X-100 is greatly determined by the high degree of constraining of the amorphous regions imposed by the grainy crystalline structure disabling the occurrence of a bulk-like α-process. Triton X-100 can be taken as a model for understanding low molecular weight materials crystallization, allowing correlating the observed dynamical behavior with the achieved crystalline morphology.

Phase transformations undergone by Triton X-100 probed by differential scanning calorimetry and dielectric relaxation spectroscopy.

The phase transformations of the surfactant Triton X-100 were investigated by differential scanning calorimetry (DSC), polarized optical microscopy (POM), and dielectric relaxation spectroscopy (DRS). In particular, crystallization was induced at different cooling rates comprised between 13 and 0.5 K min(-1). Vitrification was detected by both DSC and DRS techniques with a glass transition temperature of ∼212 K (measured on heating by DSC) allowing classifying Triton X-100 as a glass former. A fully amorphous material was obtained by cooling at a rate ≥10 K min(-1), while crystallization was observed for lower cooling rates. The temperature of the onset of melt-crystallization was found to be dependent on the cooling scan rate, being higher the lower was the scan rate. In subsequent heating scans, the material undergoes cold-crystallization except if cooled previously at a rate ≤1 K min(-1). None of the different thermal histories led to a 100% crystalline material because always the jump typical of the glass transformation in both heat flux (DSC) and real permittivity (DRS) is observed. It was also observed that the extent/morphology of the crystalline phase depends on the degree of undercooling, with higher spherulites developing for lower undercooling degree (24 K ≤ T(m) - T(cr) ≤ 44 K) in melt-crystallization and a grain-like morphology emerging for T(m) - T(cr) ≈ 57 K either in melt- or cold-crystallization. The isothermal cold- and melt-crystallizations were monitored near above the calorimetric glass transition temperature by POM (221 K) and real-time DRS (T(cr) = 219, 220, and 221 K) to evaluate the phase transformation from an amorphous to a semicrystalline material. By DRS, the α-relaxation associated with the dynamic glass transition was followed, with the observation that it depletes upon both type of crystallizations with no significant changes either in shape or in location. Kinetic parameters were obtained from the time evolution of the normalized permittivity according to a modified Avrami model taking in account the induction time. The reason the isothermal crystallization occurs to a great extent in the vicinity of the glass transition was rationalized as the simultaneous effect of (i) a high dynamic fragile behavior and (ii) the occurrence of catastrophic nucleation/crystal growth probably enabled by a preordering tendency of the surfactant molecules. This is compatible with the estimated low Avrami exponent (1.12 ≤ n ≤ 1.6), suggesting that relative short length scale motions govern the crystal growth in Triton X-100 coherent with the observation of a grainy crystallization by POM.

Changes in molecular dynamics upon formation of a polymer dispersed liquid crystal.

The molecular dynamics during the formation of a polymer dispersed liquid crystal (PDLC) was followed by dielectric relaxation spectroscopy in the frequency range from 10(-1) to 2 x 10(6) Hz and over the temperature range from 158 to 273 K. The composite was produced by thermal polymerization induced phase separation of a mixture of triethyleneglycol dimethacrylate and the nematic liquid crystal, E7, in the proportion of 60:40 w/w. Both monomer and liquid crystal vitrify upon cooling having glass transition relaxation processes already characterized by some of us; yet E7 was previously studied in a narrower frequency range, so the present work updates its dielectric behavior. The starting mixture exhibits a rather complex dielectric spectrum due to the detection of multiple processes occurring simultaneously in the monomer and liquid crystal constituents. The PDLC formation occurs by mobility changes essentially in the liquid crystal tumbling motion, while the main relaxation of the monomer depletes upon polymerization. A low intense secondary process of E7 hardly detected in the bulk material is enhanced in both starting mixture and final composite allowing its characterization.