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In this paper, we have investigated the molecular dynamics of the associating polymer, poly(mercaptopropyl)methylsiloxane (PMMS), at high pressure (up to p ∼ 505 MPa) by means of broadband dielectric spectroscopy. Previous studies revealed that PMMS exhibits two dielectric relaxation processes observed above the glass transition temperature related, most likely, to either the mobility within self-assemblies or the sub-Rouse mode (α′-slower process) and segmental (α-faster process) dynamics, whereas mechanical measurements revealed only the presence of terminal and segmental relaxations [Tarnacka et al. Macromolecules 2020, 53 (22), 10225−10233]. In order to determine the origin of the dielectric α′-process, further high-pressure experiments were performed. It was found that the timescale separation between relaxation times of segmental (α) and α′-processes is invariant to the compression, and activation volume calculated for both kinds of motions is comparable. These dynamical features are characteristic of the chain relaxation (called usually normal mode) found in type-A polymers. However, because mechanical data excluded identification of the slow dielectric relaxation as normal mode, we assigned it as the sub-Rouse process. This assignment is in the line with previous studies on poly(methylphenyl)siloxane. Further density functional theory computations revealed that the detection of the relatively strong sub-Rouse process is most likely possible due to the presence of a highly polar side group (thiol, −SH, moiety) that gives a strong contribution to dipole moment along the main polymer backbone. Additionally, we demonstrated that the pressure coefficient of the glass transition temperature, dTg/dp, in PMMS is one of the smallest among those reported to date for various polymers (dTg/dp = 156 K/GPa). This quite surprising finding was assigned to the specific interactions formed by the thiol group. Finally, it should be emphasized that high-pressure experiments turned out to be the key element to identify the sub- Rouse mode in dielectric spectraa process that might provide important information about the chain dynamics in polysiloxanes. However, to finally prove this hypothesis, further studies are required to discard the eventual possibility that the slow mode is somehow related to the nanoscopic organization in PMMS.

In this paper, several experimental techniques [X-ray diffraction, differential scanning calorimetry (DSC), thermogravimetry, Fourier transform infrared spectroscopy, and broad-band dielectric spectroscopy] have been applied to characterize the structural and thermal properties, H-bonding pattern, and molecular dynamics of amorphous bosentan (BOS) obtained by vitrification and cryomilling of the monohydrate crystalline form of this drug. Samples prepared by these two methods were found to be similar with regard to their internal structure, H-bonding scheme, and structural (α) dynamics in the supercooled liquid state. However, based on the analysis of α-relaxation times (dielectric measurements) predicted for temperatures below the glass-transition temperature (Tg), as well as DSC thermograms, it was concluded that the cryoground sample is more aged (and probably more physically stable) compared to the vitrified one. Interestingly, such differences in physical properties turned out to be reflected in the lower intrinsic dissolution rate of BOS obtained by cryomilling (in the first 15 min of dissolution test) in comparison to the vitrified drug. Furthermore, we showed that cryogrinding of the crystalline BOS monohydrate leads to the formation of a nearly anhydrous amorphous sample. This finding, different from that reported by Megarry et al. [Carbohydr. Res.2011, 346, 1061−106421492830] for trehalose (TRE), was revealed on the basis of infrared and thermal measurements. Finally, two various hypotheses explaining water removal upon cryomilling have been discussed in the manuscript.

In this work, we employed broad-band dielectric spectroscopy to determine the solubility limits of nimesulide in the Kollidon VA64 matrix at ambient and elevated pressure conditions. Our studies confirmed that the solubility of the drug in the polymer matrix decreases with increasing pressure, and molecular dynamics controls the process of recrystallization of the excess of amorphous nimesulide from the supersaturated drug–polymer solution. More precisely, recrystallization initiated at a certain structural relaxation time of the sample stops when a molecular mobility different from the initial one is reached, regardless of the temperature and pressure conditions. Finally, based on the presented results, one can conclude that by transposing vertically the results obtained at elevated pressures, one can obtain the solubility limit values corresponding to low temperatures. This approach was validated by the comparison of the experimentally determined points with the theoretically obtained values based on the Flory–Huggins theory.

Herein, broadband dielectric (BDS) and Fourier transform infrared spectroscopy (FTIR), together with differential scanning calorimetry (DSC) and X-ray diffraction (XRD), were applied to study the molecular dynamics, molecular interactions as well as physical stability of an amorphous Active Pharmaceutical Ingredient (API)-probucol (PRO)-infiltrated into anodic aluminum oxide (AAO) membranes of pore size, d ~ 10-160 nm. Interestingly, the behavior of examined substance strongly depends on the applied thermal protocol. Remarkably, for the first time, we observed that the structural dynamics of the slowly cooled PRO under confinement is significantly enhanced when compared to thatofthe quenched material. This unusual behavior was interpreted as a result of surface-induced effects (including the formation of well-resolved interfacial H-bonded layer and adsorption-desorption processes near the interface) that are magnified by the extremely high sensitivity to density fluctuation of studied PRO, reflected in the enormous pressure coefficient of the glass transition temperature dTg/dp = 427 K/GPa. In fact, FTIR investigations revealed that PRO tends to self-associate under confinement and forms a strongly bonded interfacial layer, which controls the variation in the structural dynamics of core molecules. Finally, we observed that the tendency to crystallize of confined API is reduced with respect to the bulk, even though the critical size of PRO nuclei (rc ~ 3 nm) is significantly lower than the smallest examined pore size. Nevertheless, after few weeks of storage, the investigated substance crystallized in larger pores, while it remained stable in the nanochannels of d = 10 nm. A combination of XRD and DSC measurements indicated that the infiltrated PRO forms two polymorphs, the stable form I (dominating in bulk) and unstable form II (prevailing under confinement). That means that porous matrices might be used to obtain and maintain prolonged stability of unstable polymorphic forms of API.

The impact of the chain length or dispersity of polymers in controlling the crystallization of amorphous active pharmaceutical ingredients (APIs) has been discussed for a long time. However, because of the weak control of these parameters in the majority of macromolecules used in pharmaceutical formulations, the abovementioned topic is poorly understood. Herein, four acetylated oligosaccharides, maltose (acMAL), raffinose (acRAF), stachyose (acSTA), and α-cyclodextrin (ac-α-CD) of growing chain lengths and different topologies (linear vs cyclic), mimicking the growing backbone of the polymer, were selected to probe the influence of these structural factors on the crystallization of naproxen (NAP)an API that does not vitrify regardless of the cooling rate applied in our experiment. It was found that in equimolar systems composed of NAP and linear acetylated oligosaccharides, the progress and activation barrier for crystallization are dependent on the molecular weight of the excipient despite the fact that results of Fourier transform infrared studies indicated that there is no difference in the interaction pattern between measured samples. On the other hand, complementary dielectric, calorimetric, and X-ray diffraction data clearly demonstrated that NAP mixed with ac-α-CD (cyclic saccharide) does not tend to crystallize even in the system with a much higher content of APIs. To explain this interesting finding, we have carried out further density functional theory computations, which revealed that incorporation of NAP into the cavity of ac- α-CD is hardly possible because this state is of much higher energy (up to 80 kJ/mol) with respect to the one where the API is located outside of the saccharide torus. Hence, although at the moment, it is very difficult to explain the much stronger impact of the cyclic saccharide on the suppression of crystallization and enhanced stability of NAP with respect to the linear carbohydrates, our studies clearly showed that the chain length and the topology of the excipient play a significant role in controlling the crystallization of this API.

Dielectric studies under various temperature (T) and pressure (p) conditions on five active pharmaceutical ingredients (APIs) with antifungal properties-itraconazole (ITZ), posaconazole (POS), terconazole (TER), ketoconazole (KET), and fluconazole (FLU)-were carried out. We have thoroughly studied the connection between the pressure coefficient of the glass transition temperature (dTg/dp) and the activation volume of both relaxation modes (ΔVα, ΔVδ/α') with respect to the molecular weight (Mw) or molar volume (Vm) in these systems. Besides, high pressure data revealed that the time scale separation between α- and δ- or α'-processes increases with pressure in ITZ and TER. What is more, the activation entropy, which is a measure of cooperativity, calculated from the Eyring model for the secondary (β)-relaxation in ITZ and POS, increased and decreased, respectively, in the compressed samples. To understand these peculiar results, we have carried out X-ray diffraction (XRD) measurements on the pressure-densified glasses and found that pressure may induce frustration in molecular organization and destroy the medium-range order while enhancing the short-range correlations between molecules. This finding allowed us to conclude that varying molecular spatial arrangement is responsible for the extraordinary dynamical behavior of ITZ, POS, and TER at high pressure.

Herein we show that the nanostructured interface obtained via modulation of the pore size has a strong impact on the segmental and chain dynamics of two poly(propylene glycol) (PPG) derivatives with various molecular weights (Mn = 4000 g/mol and Mn = 2000 g/mol). In fact, a significant acceleration of the dynamics was observed for PPG infiltrated into ordinary alumina templates (Dp = 36 nm), while bulklike behavior was found for samples incorporated into membranes of modulated diameter (19 nm < Dp < 28 nm). We demostrated that the modulation-induced roughness reduces surface interactions of polymer chains near the interface with respect to the ones adsorbed to the ordinary nanochannels. Interestingly, this effect is noted despite the enhanced wettability of PPG in the latter system. Consequently, as a result of weaker H-bonding surface interactions, the conformation of segments seems to locally mimic the bulk arrangement, leading to bulklike dynamics, highlighting the crucial impact of the interface on the overall behavior of confined materials.

In this paper, broadband dielectric spectroscopy (BDS) has been applied to study the molecular dynamics and crystallization kinetics of the antihyperlipidemic active pharmaceutical ingredient (API), gemfibrozil (GEM), as well as its deuterated (dGEM) and methylated (metGEM) derivatives, characterized by different types and strengths of intermolecular interactions. Moreover, calorimetric and infrared measurements have been carried out to characterize the thermal properties of examined samples and to probe a change in the H-bonding pattern in GEM, respectively. We found that the dielectric spectra of all examined compounds, collected below the glass transition temperature (Tg), reveal the presence of two secondary relaxations (β, γ). According to the coupling model (CM) predictions, it was assumed that the slower process (β) is of JG type, whereas the faster one (γ) has an intramolecular origin. Interestingly, the extensive crystallization kinetics measurements performed after applying two paths, i.e., the standard procedure (cooling and subsequently heating up to the appropriate temperature, Tc), as well as annealing at two temperatures in the vicinity of Tg and further heating up to Tc, showed that the annealing increases the crystallization rate in the case of native API, while the thermal history of the sample has no significant impact on the pace of this process in the two derivatives of GEM. Analysis of the dielectric strength (Δe) of the α-process during annealing, together with the results of Fourier transform infrared spectroscopy (FTIR) measurements, suggested that the reorganization within dimeric structures formed between the GEM molecules is responsible for the observed behavior. Importantly, our results differ from those obtained by Tominaka et al. (Tominaka, S.; Kawakami, K.; Fukushima, M.; Miyazaki, A.Physical Stabilization of Pharmaceutical Glasses Based on Hydrogen Bond Reorganization under Sub-Tg Temperature Mol. Pharm. 2017 14 264 273 10.1021/acs.molpharmaceut.6b00866.), who demonstrated that the sub-Tg annealing of ritonavir (RTV), which is able to form extensive supramolecular hydrogen bonds, protects this active substance against crystallization. Therefore, based on these contradictory reports, one can hypothesize that materials forming H-bonded structures, characterized by varying architecture, may behave differently after annealing in the vicinity of the glass transition temperature.

Infrared and dielectric spectroscopy, X-ray diffraction, and density functional theory computations have been used to study the hydrogen-bonding pattern, molecular dynamics, internal structure, and dipole moment distribution in 2-ethyl-1-hexanol, 2-ethyl-1-hexylamine, 2-ethyl-1-hexanethiol, and 1-phenyl-2-butanol. Dielectric investigations revealed that Kirkwood–Frohlich correlation factor is much larger or lower than the unity in the vicinity of the glass transition, dependent on the compound. It indicates that change in the functionality of the H-bonding moiety influences the architecture of the supramolecular nanoassemblies. Further thorough experimental and theoretical considerations confirmed this hypothesis. Moreover, it was found that not the strength of hydrogen bonds itself, but the diverse population of nanoassociates, their size, and the spatial organization of the molecules in clusters have a strong influence on the appearance/absence as well as the intensity of the Debye relaxation. The resul...

In this paper, we report comprehensive studies on the molecular dynamics of a series of poly(propylene glycol) (PPG) derivatives characterized by three different terminal groups and various molecul...

In this paper, we explored the influence of both the variation in the molecular weight (Mn = ∼400, 2000, 4000 g/mol) and the terminal groups (hydroxyl, amino, and methoxy) on the molecular dynamics of poly(propylene glycols) confined within anodic aluminum oxide membranes of different pore diameters. All confined samples revealed the presence of two glass transition temperatures related to the vitrification of two, core and interfacial, fractions of polymers. As found, the glass transition temperature of PPG adsorbed on the pore walls increases with a decrease in polymer Mn and scales with the H-bonding ability of a given material. Surprisingly, the glass transition temperature of the core macromolecules decreases with respect to the bulk sample with increasing Mn. To gain insight into the observed quite unexpected anti-correlated behavior of both Tg values, we performed the additional contact angle and surface tension measurements together with the annealing experiments. As shown, there were no differenc...

The behavior of the low- and high-molecular weight glass formers confined in nanoporous templates remains an unsolved puzzle despite the intensive long-term studies in this matter. Special effort is taken to understand the enhancement of segmental or structural dynamics and the depression of the glass-transition temperatures, Tgs in materials infiltrated in pores of the nanometric size. In this paper, we have analyzed dielectric, calorimetric, and contact angle data collected for various systems to determine which factors are responsible for these effects. It turned out that with increasing interfacial energy, molecules attached to the pore walls (interfacial layer) vitrify at higher temperatures. Moreover, the dynamics of core molecules starts to deviate from bulk-like behavior. Therefore, a greater depression of the glass-transition temperature, Tg, of this fraction of molecules is noted. Also, it was found that the sensitivity of structural dynamics to the density fluctuations, quantified by the pressu...

Herein, we tested the validity of the thermodynamic scaling of two (α and δ) relaxation processes observed in the isotropic and nematic phases of itraconazole, that is classified as a liquid crysta...

In this paper, the crystal growth of three active pharmaceutical ingredients (APIs), griseofulvin, nifedipine, and naproxen, from the single component systems and the solid dispersions composed of APIs and acetylated maltose, has been investigated in a wide temperature range using optical microscopy. Additionally, complementary calorimetric and dielectric measurements have been carried out to characterize thermal properties and molecular dynamics of prepared samples. We found that close to the glass transition temperature (Tg), there is a sharp change in the T-dependence of the crystal growth rates (μcg) of APIs in four studied systems. Consequently, the activation barrier for the crystal growth (Ecg) calculated above and below this temperature differs significantly, indicating a change in the kinetics of this stage of crystallization. Furthermore, it was demonstrated that at T ≈ 1.25–1.3Tg, which may correspond to the crossover temperature (TB) related to the variation in molecular dynamics, a maximum in...

In this paper, we have investigated the molecular dynamics above and below the glass-transition temperature of bisphenol-A diglycidyl ether (known as DGEBA, Mn = 340 g/mol) infiltrated in nanoporous alumina (AAO) templates of various pore sizes by means of dielectric and Raman spectroscopies. It was found that the temperature dependence of the structural relaxation times is different under confinement with respect to the bulk sample even in the high-temperature regime. Interestingly, below the glass-transition temperature, the slow secondary process (β) was not detected in dielectric loss spectra of confined DGEBA, while the relaxation times of the faster secondary process (γ) were unaffected by the pore size. To explain this phenomenon, two different scenarios, considering either suppression of the motions related to this mobility or enhancement of its dynamics, were taken into account. Additional annealing experiments, which lead to density perturbation, enabled us to recover bulk-like temperature depen...

In this article, thermal properties, molecular dynamics, crystallization kinetics, and intermolecular interactions in pure naproxen (NAP), its amide (NH2–NAP), and four esters (methyl, Met-NAP; iso...

The effect of the chemical modification of poly(propylene glycol) (PPG) end groups on the molecular dynamics under 2D confinement and the polymer/matrix interactions (including interfacial energies) was investigated by a combination of differential scanning calorimetry (DSC), broadband dielectric spectroscopy (BDS), surface tension and contact angle measurements. The replacement of −OH groups in native PPG allowed to modify the interactions with the hydroxyl groups attached to the pore walls of nanoporous aluminum oxide (AAO) membranes of various pore diameter. It was found that the observed reduction in the glass transition temperature (Tg) of the core polymers correlates well with a general trend (the higher the solid–liquid interfacial tension, γSL, the lower Tg,confined) reported earlier. Moreover, we demonstrated that although the interfacial solid–liquid energy seems to be almost the same for each studied herein material, a clear change in the crossover temperature (Tc), related to the vitrification...

In this paper the crystal growth of nifedipine from pure system and from binary mixtures composed of active substance (API) and two acetylated disaccharides, maltose and sucrose (NIF-acMAL, NIF-acSUC, 5:1 weight ratio), was investigated. Optical snapshots supported by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) measurements showed that mainly β and α forms of nifedipine grow up in all investigated samples. They also revealed that the morphology of growing crystals strongly depends on the presence of modified carbohydrates and temperature conditions. Interestingly, it was found that the activation barrier for the crystal growth of the β polymorph is not affected by acetylated saccharides while the one estimated for the α form changes significantly from 48.5 kJ/mol (pure API) up to 122 kJ/mol (NIF-acMAL system). Moreover, the relationship between the crystal growth rate and structural relaxation times for pure NIF and solid dispersions were analyzed. It turned out that there is a clear decoupling between the crystal growth rate and structural dynamics in both NIF-acMAL and NIF-acSUC binary mixtures. This is in line with recent reports indicating the decoupling phenomenon to be a universal feature of soft matter in the close vicinity of the glass transition temperature.

The effect of 2D confinement on the dynamics of the normal mode (chain mobility) and segmental relaxation in poly(propylene glycol) (PPG) has been studied with the use of broadband dielectric spectroscopy (BDS) and differential scanning calorimetry (DSC). It is shown that both processes become faster with increasing degree of confinement. Interestingly, the crossover from VFT to the Arrhenius-like behavior of chain and segmental dynamics, observed in the examined system, is strictly related to the vitrification of the adsorbed polymers. We also report that the mean relaxation times of the normal, τNM, and segmental modes, τα, depend on the thermal history of confined PPG and can be significantly modified using different thermal treatments. It is demonstrated that annealing of the samples below the crossover temperature, Tc, leads to a systematic shift of the segmental relaxation and normal mode toward lower frequencies, resulting in an increase in the glass transition temperature of the spatially restrict...

The dynamics and thermodynamics of confined triphenyl phosphite (TPP) were studied using broadband dielectric spectroscopy (BDS) and differential scanning calorimetry (DSC). Geometric confinement in channels having length scales commensurate with the molecular size of TPP causes bifurcation of the dynamics: two populations are observed, distinguished by their reorientational mobilities and glass transition temperatures. Upon cooling, significant changes in the relaxation process and temperature dependence occur due to the slow vitrification of the molecules in close proximity to the interface. Such a kinetic aspect of glass formation is unusual. This surface interaction alleviates constraints on the molecules, allowing their glass transition to shift to lower temperatures. Simultaneously, it was observed that the structural relaxation process shifts to lower frequencies, and the distribution of the relaxation times becomes narrower upon annealing. This effect is especially visible at lower frequencies, in...

The crystallization and melting behavior of phenyl salicylate under confinement were studied by means of dielectric spectroscopy (BDS) and differential scanning calorimetry (DSC). From the analysis of the kinetics of crystallization we established that crystals formed in bulk and under confinement are characterized by varying the rate of growth, dimensionality, and crystal lattice. It was shown that depending on the degree of confinement the crystallization can be accelerated or suppressed completely. Interestingly, we also found that the activation barrier for the crystallization either increases or decreases with respect to the bulk conditions. Further investigation of the melting temperature of the formed crystals indicated unequivocally that it is connected to the formation of different polymorphic forms of salol. Additional FTIR measurements confirmed that thesis. Based on calorimetric data obtained for the confined samples, we concluded that at pores of higher diameter the unstable (monoclinic) form...

Dielectric spectroscopy and differential scanning calorimetry (DSC) were applied to study the molecular dynamics and thermal properties of a low-molecular-weight glass-forming liquid, salol (phenyl...

Differential scanning calorimetry (DSC), broadband dielectric (BDS), and Fourier transform infrared (FTIR) spectroscopies as well as theoretical computations were applied to investigate inter- and intramolecular interactions between the active pharmaceutical ingredient (API) indomethacin (IMC) and a series of acetylated saccharides. It was found that solid dispersions formed by modified glucose and IMC are the least physically stable of all studied samples. Dielectric measurements showed that this finding is related to neither the global nor local mobility, as the two were fairly similar. On the other hand, combined studies with the use of density functional theory (DFT) and FTIR methods indicated that, in contrast to acetylated glucose, modified disaccharides (maltose and sucrose) interact strongly with indomethacin. As a result, internal H-bonds between IMC molecules become very weak or are eventually broken. Simultaneously, strong H-bonds between the matrix and API are formed. This observation was used to explain the physical stability of the investigated solid dispersions. Finally, solubility measurements revealed that the solubility of IMC can be enhanced by the use of acetylated carbohydrates, although the observed improvement is marginal due to strong interactions.

Recently it was reported that upon mechanical milling of pure furosemide significant chemical degradation occurs (Adrjanowicz et al. Pharm. Res.2011, 28, 3220-3236). In this paper, we present a novel way of chemical stabilization amorphous furosemide against decomposing that occur during mechanical treatment by preparing binary mixtures with acylated saccharides. To get some insight into the mechanism of chemical degradation of furosemide induced by cryomilling, experimental investigations supported by density functional theory (DFT) computations were carried out. This included detailed studies on molecular dynamics and physical properties of cryoground samples. The main thrust of our paper is that we have shown that furosemide cryomilled with acylated saccharides forms chemically and physically stable homogeneous mixtures with only one glass transition temperature, Tg. Finally, solubility measurements have demonstrated that furosemide cryomilled with acylated saccharides (glucose, maltose and sucrose) is much more soluble with respect to the crystalline form of this active pharmaceutical ingredient (API).

Broadband dielectric measurements were carried out in the supercooled as well as in the glassy state of two very important disaccharides: trehalose and sucrose. Multiple relaxation processes were observed. Above the glass transition temperatures of examined disaccharides structural relaxation of cooperative origin was detected, where in the glassy state more local motions (secondary modes) appeared. Our data were discussed in light of the findings reported by other groups. We pointed out that sample preparation might impact mobility and, thus, dielectric loss spectra in a significant way. Consequently, it may lead to misinterpretation of the dielectric relaxation processes. Moreover, impact of physical aging and pressure on dynamics of two secondary relaxation processes observed in the glassy state of trehalose and sucrose has been investigated. Additionally, we have demonstrated that, in contrast to the calorimetric measurements (DSC), activation energies of the β- and γ-relaxation processes observed in the glassy state of sucrose and trehalose do not change as a result of physical aging. Finally, we found out that the β-relaxation process slows down as pressure increases. We interpreted this fact in view of increasing rigidity of the structures of disaccharides.

The main goal of this paper is to identify the molecular origins of two secondary relaxations observed in mechanical as well as in dielectric spectra in polysaccharides, including cellulose, and starches, such as pullulan and dextran. This issue has been actively pursued by many research groups, but consensus has not been reached. By comparing experimental data of monosaccharides, disaccharides, and polysaccharides, we are able to make conclusions on the origins of two secondary relaxations in polysaccharides. The faster secondary relaxations of polysaccharides are similar to the faster secondary relaxations of mono-, di-, and oligosaccharides. These include comparable relaxation times and activation energies in the glassy states, and also all the faster secondary relaxations have larger dielectric strengths than the slower secondary relaxation. The similarities indicate that the faster secondary relaxations in the polysaccharides have the same origin as that in mono-, di-, and oligosaccharides. Furthermore, since the relaxation time of the faster secondary relaxation in several mono- and disaccharides was found to be insensitive to applied pressure, the faster secondary relaxations of the polysaccharides are identified as internal motions within their monomeric units. The slower secondary relaxations in polysaccharides also have similar characteristics to those of the slower secondary relaxations of the disaccharides (maltose, cellobiose, sucrose, and trehalose), which indicates the analogous motions govern the slower process in these two groups of carbohydrates. Earlier we have shown in disaccharides that the rotation of the monomeric units around the glycosidic bond is responsible for this process. The same motion can occur in polysaccharides in the form of a local chain rotation. These motions involve the whole molecule in disaccharides and a local segment in polysaccharides. It is intermolecular in nature (with relaxation time pressure dependent, as found before in a disaccharide), and hence, it is the precursor of the structural alpha-relaxation. These results lead us to identify the slower secondary relaxation of the polysaccharides as the Johari-Goldstein beta-relaxation, which is supposedly a universal and fundamental process in all glass-forming substances.

Broadband dielectric relaxation measurements of tris(dimethylsiloxy)phenylsilane were made at ambient pressure and at elevated pressures. The data show an anomalous behavior not previously seen in any other glass-formers; namely, the structural alpha-relaxation loss peak narrows with increasing pressure and temperature at constant peak frequency. Interpreted by the coupling model, the effect is due to reduction of intermolecular coupling at elevated pressures. This interpretation has support from the observed decrease of the separation between the alpha-relaxation and the Johari-Goldstein secondary relaxation, as well as the smaller steepness or "fragility" index m of the data obtained at 1.7 GPa than at ambient pressure.