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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 kinetics of polymerization of Bisphenol-A diglycidyl ether (DGEBA), a well-known epoxy resin, with two ionic amines 1-(3-aminopropyl)-3-butylimidazolium bis(trifluoromethylsulfonyl)imide ([apbim][NTf2]) and the tetrabutylammonium leucine ([N4444][Leu]) have been studied with the use of differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS) at various temperatures. We found many fundamental differences between the progress of this reaction with respect to the classical system (curing of epoxy resin with ordinary nonconducting hardeners). One of the most significant differences is related to the mechanism of polymerization. It is worthwhile to mention that usually the autocatalytic model is used to describe the curing of DGEBA with ordinary amines. However, herein, the kinetic curves followed a clearly exponential shape characteristic of first-order kinetics. We claim that the change in mechanism of polymerization is related to the presence of a conducting amine that acts as...

We examined the behavior of poly(mercaptopropyl)methylsiloxane (PMMS), characterized by a polymer chain backbone of alternate silicon and oxygen atoms substituted by a polar pendant group able to form hydrogen bonds (−SH moiety), by means of infrared (FTIR) and dielectric (BDS) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and rheology. We observed that the examined PMMS forms relatively efficient hydrogen bonds leading to the association of chains in the form of ordered lamellar-like hydrogen-bonded nanodomains. Moreover, the recorded mechanical and dielectric spectra revealed the presence of two relaxation processes. A direct comparison of collected data and relaxation times extracted from two experimental techniques, BDS and rheology, indicates that they monitor different types of the mobility of PMMS macromolecules. Our mechanical measurements revealed the presence of Rouse modes connected to the chain dynamics (slow process) and segmental relaxation (a faster process), whereas in the dielectric loss spectra we observed two relaxation processes related most likely to either the association–dissociation phenomenon within lamellar-like self-assemblies or the sub-Rouse mode (α′-slower process) and segmental (α-faster process) dynamics. Data presented herein allow a better understanding of the peculiar dynamical properties of polysiloxanes and associating polymers having strongly polar pendant moieties.

Herein, we explored thermal properties, dynamics, wettability, and Hbonding pattern in various poly(propylene glycols) (PPG) of Mn = 400 g/mol confined into two types of nanoporous templates: silica (d = 4 nm) and alumina (d = 18 nm). Unexpectedly, it was found that the mobility of the interfacial layer and the depression of the glass transition temperature weakly depend on the pore size, surface functionalization, and wettability. However, interestingly, we have reported strengthening of the hydrogen bonds in samples confined in silica pores. Further, the unique annealing experiments on PPG-OH with the use of Fourier transform infrared spectroscopy revealed the reorganization of oligomers close to the interface and the formation of three distinct fractions, interfacial, intermediate, and bulk-like, in the infiltrated samples. These experiments might shed new light on the variation of the segmental/structural relaxation times due to annealing of materials of different molecular weights infiltrated into pores or deposited in the form of a thin layer.

In this work, we developed a fast, highly efficient, and environmentally friendly catalytic system for classical free-radical polymerization (FRP) utilizing a high-pressure (HP) approach. The application of HP for thermally-induced, bulk FRP of 1-vinyl-2-pyrrolidone (VP) allowed to eliminate the current limitation of ambient-pressure polymerization of ‘less-activated’ monomer (LAM), characterized by the lack of temporal control yielding polymers of unacceptably large disperisites and poor result reproducibility. By a simple manipulation of thermodynamic conditions (p = 125–500 MPa, T = 323–333 K) and reaction composition (two-component system: monomer and low content of thermoinitiator) well-defined poly(1-vinyl-2-pyrrolidone)s (PVP) in a wide range of molecular weights and low/moderate dispersities (Mn = 16.2–280.5 kg mol−1, Đ = 1.27–1.45) have been produced. We have found that HP can act as an ‘external’ controlling factor that warrants the first-order polymerization kinetics for classical FRP, something that was possible so far only for reversible deactivation radical polymerization (RDRP) systems. Importantly, our synthetic strategy adopted for VP FRP enabled us to obtain polymers of very high Mn in a very short time-frame (0.5 h). It has also been confirmed that VP bulk polymerization yields polymers with significantly lower glass transition temperatures (Tg) and different solubility properties in comparison to macromolecules obtained during the solvent-assisted reaction.

In this paper, the molecular dynamics, H-bonding pattern and wettability of the primary and secondary monohydroxyalcohols, 2-ethyl-1-hexanol (2E1H), 2-ethyl-1-butanol (2E1B) and 5-methyl-3-heptanol (5M3H) infiltrated into native and functionalized silica and alumina pores having pore diameters, d = 4 nm and d = 10 nm, have been studied with the use of Broadband Dielectric (BDS) and Fourier Transform InfraRed (FTIR) spectroscopies, as well as contact angle measurements. We found significant differences in the behavior of alcohols forming chain- (2E1H, 2E1B) or micelle-like (5M3H) supramolecular structures despite of their similarities in the wettability and interfacial energy. It turned out that nanoassociates as well as H-bonds are more or less affected by the confinement dependently on the chemical structure and alcohol order. Moreover, a peculiar behavior of the self-assemblies at the interface was noted in the latter material (5M3H). Finally, it was found that irrespectively to the sample, type of pores, functionalization, the temperature evolution of Debye relaxation times, τD, of the confined systems deviates from the bulk behavior always at similar τD due to vitrification of the interfacial layer. This finding is a clear indication that unexpectedly dynamics (mobility) of the supramolecular structures close to the hydrophilic and hydrophobic surfaces is similar in each system.

The vitrification process is usually preceded by a significant change (around 6–8 decades) in the viscosity, structural relaxation times, or diffusion that occurs in a relatively small range of temperatures in fragile liquids. Along with this phenomenon, conformations of the molecules vary as well. In fact, this process is studied in bulk polymers and high molecular weight materials deposited in the form of thin films. On the other hand, spatial rearrangement of small glass formers in the supercooled liquid state has not been intensively investigated, so far. Herein, data obtained from measurements carried out using various experimental techniques on supercooled 1,2,3,4,6-penta-O-(trimethylsilyl)-D-glucopyranose (S-GLU) have revealed that rotations of silyl moieties along with the deformation in the saccharide ring are significantly slowed down in the vicinity of the glass transition temperature (Tg). These intramolecular reorganizations affect the structural relaxation time, atomic pair distribution function, integrated intensity, as well as a number of bands and signals observed, respectively, in the Raman and NMR spectra. Data reported herein offer a better understanding of the conformational variation and time scale of this process in the complex and flexible molecules around the Tg.

We report, for the first time, the metal-free green synthesis of linear poly(vinyl pyrrolidone) (PVP) homopolymers of molecular weight higher than 100 kg mol and narrow dispersities via thermal and photo-induced free radical polymerisation carried out within alumina nanoporous membranes acting as >nanoreactors>., K. K. and M. T. are thankful for financial support from the Polish National Science Centre within SONATA Bis project (Dec. no. 2015/18/E/ST4/00320). M. T. is thankful for financial support from the Foundation for Polish Science (FNP). L. L.-B. and C. M. acknowledge MINECO for financial support (MAT2017-83014-C2-2-P).

Poly(1-vinyl-2-pyrrolidone) (Povidone, PVP) is one of the most interesting and versatile synthetic polymers utilised in the pharmaceutical and cosmetic industries. Its large-scale commercial production offers an assortment of products in a wide range of molecular weights but poorly-controlled (macro)structural parameters (i.e., dispersity, functionality) limiting the efficiency of PVP-based drug delivery systems (DDS). In this work, synthesised linear and star-shaped PVPs with a strictly defined structure and functionality were compared with the linear, commercially-supplied product and explored as potential vehicles for physical entrapment of metronidazole (MTZ). Here, a question is addressed how differences in their macromolecular properties affect the amorphisation of MTZ, drug encapsulation, the stability of drug-loaded micellar structures and their in vitro release from the carrier. The X-ray diffraction studies and calorimetric measurements revealed that MTZ crystallises in all investigated herein systems reducing the glass transition temperature of the binary mixture significantly. Transmission electron microscopy and dynamic light scattering analysis revealed that MTZ-loaded DDS are able to form ultrasmall regular nanocarriers with an increasing effect of regularity and sphericity from star-shaped DDS to linear-based ones. We founded that synthesised linear-based DDS is the most effective for MTZ entrapment (PVP:MTZ = 1:1 weight ratio) due to their smallest hydrodynamic radius dh = 14.7 nm, the highest stability of micellar structures −2.37 mV, and the highest values of loaded drug 76.5%. Moreover, all applied PVP-based DDS revealed an initial burst release effect of MTZ (pH = 7.4) reaching up to 60% of drug released within the first 5 h (the first-order release model fits). The marked efficiency of MTZ-loaded DDS of strictly defined structural parameters indicates the great importance of polymer preparation strategy in the targeted therapy.

The synthesis of well-defined imidazolium-based poly(ionic liquid)s (PILs) by reversible addition–fragmentation chain transfer (RAFT) polymerization is demonstrated. Two specially designed monomeric ionic liquids (MILs), such as 1-methyl-3-vinylimidazolium bis(trifluoromethanesulfonyl)imide [MVIM][NTf2] and 1-ethyl-3-vinylimidazolium bis(trifluoromethanesulfonyl)imide [EVIM][NTf2] were polymerized with the 2,2′-azobisisobutyronitrile (AIBN) initiator in the presence of a trithiocarbonate RAFT agent. Depending on the varied ratios of the monomer to CTA ([monomer]/[CTA] = 100/1; 400/1; 1000/1) we obtained P[MVIM][NTf2] and P[EVIM][NTf2] homopolymers with the number-average molecular weights (Mn) in a broad range Mn = 2.5–340.0 kDa and Mn = 2.1–450.0 kDa, respectively. The controlled character of the polymerization of each ionic monomer was confirmed by the pseudo-first order kinetic, a linear increase in the Mn with conversion and relatively narrow dispersity indices (Đ = 1.09–1.37 for P[MVIM][NTf2] and Đ = 1.10–1.41 for P[EVIM][NTf2]). Additionally, the obtained macromolecules are characterized by the enhanced/or comparable conductivity in comparison with those reported in the literature [Wojnarowska et al., Macromolecules, 2014, 47, 4056–4065 and Fan et al., Macromolecules, 2016, 49, 4557–4570], indicating that we are able to produce polymers of high molecular weights characterized by relatively high conductivity (σdc ∼ 10−9 at Tg). Finally, we found quite unexpected evolution of Tgvs. Mn of the produced polymers in the limit of low molecular weight, which seems to correspond to those observed in the case of van der Waals polymers such as polystyrene or polyisobutylene.

Comprehensive FTIR studies on the progress of mutarotation in D-fructose mixed with maltitol have been carried out over a wide range of temperatures, both above and below the glass transition temperature Tg. In addition to the analysis of single bands, we have developed a completely new approach considering the full spectral range to follow the overall progress of the reaction. We have found that at the calorimetric Tg, there is a clear change in the temperature dependence of constant rates. The activation barrier for mutarotation changes from around 59 kJ mol−1 (the supercooled state) to around 249 kJ mol−1 (the glassy state). This dramatic variation in the activation barrier is consistent with the change in the mechanism of this specific chemical conversion, as theoretically considered by Wlodarczyk et al. [Phys. Chem. Chem. Phys., 2014, 16, 4694–4698]. Alternatively, it can also be connected to the change in the viscosity of the sample. Additionally, we investigated the relationship between constant rates (k) of mutarotation, structural relaxation times (τα), and dc conductivity (σdc) above and below the glass transition temperature. It was found that there was a linear correlation between all these quantities; they scale with various exponents changing at Tg. Our results also indicate that a single activation barrier might not be sufficient to describe the mutarotation process.

The development of a green e-caprolactone (CL) polymerization method is the most important challenge in modern polymer chemistry. Herein, we propose a novel method to produce polyesters of a well-defined chemical structure, and narrow molecular weight distributions by using a combination of high pressure, temperature and water. We found two competitive phenomena: polymerization and crystallization occurring at high compression. Once the latter process is avoided, the control over the reaction is reached. By varying the thermodynamic conditions and concentration of water molecules, polymers of moderate molecular weights (Mn = 1.6–19.0 kg mol−1) and dispersities (Đ ≈ 1.07–1.50) could be produced. Additional NMR experiments supported by further MALDI TOF analysis enabled us to determine telechelic hydroxyl and carboxylic/acidic moieties as terminal groups of produced PCLs. Finally, the latter measurements also indicated that generally an increase in dispersity above 1.3 is strongly related to the competitive reactions leading to the production of cyclic polyesters. The presented results open up alternative routes to produce PCLs of enhanced biocompatibility and biodegradability using the greenest method reported to date.

In this work, we examine in detail the crystallization tendency of the model glass-forming liquid indomethacin at varying thermodynamic conditions. To do that, we combine experimental results with predictions of the classical theories of nucleation and growth. We have considered changes in the crystallization rate k along iso-invariant curves located differently in the T–p phase diagram of the studied supercooled liquid. We include for the first time temperature and pressure conditions along which the thermodynamic driving force toward crystallization, commonly discussed as the difference in the chemical potential of the liquid/crystalline phases, Δμ, is expected to remain constant. Although the increase in pressure fosters crystallization (due to an increasing overlap of the nucleation and growth rates maxima), we show that when moving along certain thermodynamic paths the crystallization rate remains unchanged, or it is only slightly affected by the density increase. Therefore, by studying the kinetics ...

Controlling crystallization and glass-forming tendencies of molecular liquids is of great scientific and practical importance. In the present work, we show that a lot can be learned regarding this process by introducing temperature and pressure as thermodynamic control variables. For the glass-forming liquid ketoprofen and its non-hydrogen bonded analogue, we have investigated changes in the crystallization rate along different isolines located in the two-dimensional T–p phase space. This has included isobaric (p = const), isothermal (T = const), and isochronal (τα = const) data. Our results reveal that the crystallization tendency of the investigated liquids can be tuned by moving along specific thermodynamic pathways. In particular, we highlight that among considered isolines the overall crystallization rate is the least affected by the density increase for the isochronal (T, p) state points. Interestingly, for various thermodynamic conditions with the same τα the estimated value of the thermodynamic dr...

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...

In this paper, thermal and structural properties, as well as molecular dynamics of co-amorphous binary mixtures composed of itraconazole (ITZ) and four other active pharmaceutical ingredients (APIs) with antifungal activity (posaconazole (POS), ketoconazole (KET), fluconazole (FLU), and voriconazole (VOR)), have been investigated. Calorimetric measurements indicated that with increasing concentration of each excipient (EXC), the glass transition temperature and phase transition temperatures, related to the formation of nematic and smectic order, are affected in the binary systems. Comprehensive analysis of the enthalpy of isotropic-nematic transition and the temperature dependence of the order parameter, calculated from infrared data for selected mixtures, supported by the results of X-ray diffraction , enabled us to confirm the suppression of liquid crystalline (LC) ordering in ITZ by KET, FLU, and VOR. On the other hand, ITZ enforced the nematic-like molecular arrangement of POS. Further dielectric measurements revealed that the type of EXC and its content in the mixture have no impact on the ratio of α- and δ-relaxation times (τα and τδ, respectively) in ITZ. Moreover, it was shown that δ-process is more sensitive to the isotropic-nematic phase transition than the α-one, and the formation of the nematic phase in this API occurs at different τα and τδ, dependently on the type of EXC and its concentration in the mixture. Summarizing, the results of our studies are much different with respect to those reported previously by Kozyra et al. [Mol. Pharm. 15 (2018) 5192–5206] and by some of us [Kaminska et al. Eur. J. Pharm. Biopharm. 88 (2014) 1094–1104] for ITZ mixed with various polymers and acetylated maltose, respectively. This finding clearly indicates that there is a different impact of the low and high molecular weight excipients on the ability in the formation of LC phases in ITZ, which may have important implications for the further development of the formulations of this pharmaceutical.

In this paper, we have studied the effect of both hard confinement (nanoporous membranes treated as nanoreactors) and high pressure (compression of system) on the progress of free-radical (FRP) and reversible addition-fragmentation chain transfer (RAFT) polymerizations of selected hardly polymerizable, sterically hindered imidazolium-based ionic monomer 1-octyl-3-vinylimidazolium bis(trifluoromethanesulfonyl)imide ([OVIM][NTf2]). These two innovative approaches, affecting (in a different way) the free volume of the polymerizing system, allows the reduction of the number of toxic substrates/catalysts, satisfying the requirement of green chemistry. It was found that at both conditions (high compression and confinement) the polymerizability of monomer, as well as the control over the reaction and the properties of the produced polyelectrolytes, have increased significantly. However, it should be added that there were noticeable differences between FRP carried out under confinement and at high pressures. Interestingly, by appropriate variation in thermodynamic conditions, it was possible to synthesize polymers of moderate molecular weight (Mn ∼ 58 kg mol−1) and relatively low dispersity (Đ ∼ 1.7); while for the reaction performed within AAO pores of varying diameter (d = 35 nm and d = 150 nm), macromolecules of higher Mn but slightly broader dispersity indices (Đ ∼ 2.2–2.7) were recovered. On the other hand, RAFT polymerization carried out under confinement and at elevated pressures yielded polymers with well-defined properties. Noteworthy is also the fact that nanopolymerization leads to polymers of comparable Mn to those obtained at high-pressure studies but at significantly shorter reaction time (t ∼ 2 hours). We believe that the presented data clearly demonstrated that both examined approaches (the compression and application of alumina templates, treated as nanoreactors) could be successfully used as additional driving forces to polymerize sterically hindered monomers and produce well-defined polymers in relatively short times. At the same time, it should be mentioned that both proposed polymerization methods enabled us to omit the addition of metal-based initiators/catalysts, which seem to be a crucial step towards further development of the alternative green synthesis of polyelectrolytes in the future.

In this paper, we present facile synthetic strategies enabling production of well-defined poly(ionic liquids) PILs based on 1-vinyl-4-benzyl-3-methylimidazolium- (VBIm) and 1-vinyl-4-benzyl-3-methylpyrrolidium (VBPy) ionic liquids (IL) possessing different counterions (chloride Cl− vs. bis(trifluoromethanesulfonyl)imide NTf2-) (VBIm/NTf2,VBIm/Cl, VBPy/NTf2,VBPy/Cl). The reaction routes have been selected to design two types of polyelectrolytes i) linear homopolymers showing solid-like behavior and ii) grafted copolymers composing of poly(siloxane) segments extended with analogous ionic domains that shows gel-like behavior. The former one has been produced via controlled radical polymerization methods (CRP) such as atom transfer radical polymerization (ATRP) or reversible addition fragmentation chain-transfer polymerization (RAFT), whereas the second one using thiol-ene coupling photo-polymerization. It was found that the glass transition temperature, Tg, of the synthesized herein linear homopolymer-based systems (both VBIm/NTf2 and VBPy/NTf2- -based) increases with their molecular weight, Mn, similarly as reported for its N-conjugated analogs described in our previous study [Maksym et al.,Polym. Chem., 2017, 8, 5433]. However, they are characterized by markedly lower conductivity, σdc (σdc~10−15 S/cm vs.σdc~10−16S/cm for PVBIm/NTf2 vs. PVBPy/NTf2- at Tg determined from calorimetric experiments) when compared to N-conjugated one (σdc~10−9 S/cm for poly(N-vinyl-imidazole)/NTf2). Interestingly, the ionic conductivity value at Tg of grafted is similar to its corresponding linear analogs. Nevertheless, at T = 293K both anhydrous linear and grafted imidazolium-based PILs are characterized by high σdc, reaching values σdc~10−4S/cm and σdc~10−7S/cm, respectively.

Differential Scanning Calorimetry (DSC), X-ray diffraction (XRD), Fourier Transform Infrared (FTIR) and Broadband Dielectric (BD) spectroscopies were applied to investigate the thermal, structural, photochemical and dynamical properties of a fulgide-type photochromic compound, Aberchrome 670 (Ab670). In the original crystals, characterized by a pale yellow color, molecules take the E conformation. However, upon UV irradiation of either the crystalline or glassy compound, it isomerizes to the closed (C) form, characterized by the intense red tone. Although, we have found that such conversion is not complete (far below 100%). It was shown that due to UV irradiation as well as heating of the studied fulgide to high temperature (above the melting point), the Z isomer is formed. Further FTIR measurements performed on the UV irradiated and molten compound indicated that upon annealing of the sample in the vicinity of the glass transition temperature the Z isomer reverts back to the original E form. The final confirmation of this supposition has come from BDS studies, where the strong shift of the structural relaxation process during time-dependent isothermal measurements was noticed. One can add that a similar pattern of behavior has been observed previously by some of us in the case of tautomerism or mutarotation [Z. Wojnarowska et al., J. Chem. Phys., 2010, 133, 094507; W. Kossack et al., J. Chem. Phys., 2014, 140, 215101; P. Wlodarczyk et al., J. Phys. Chem. B, 2009, 113, 4379-4383; P. Wlodarczyk et al., J. Non-Cryst. Solids, 2010, 356, 738-742]. From the analysis of the time variation of the structural relaxation times, the activation barrier, EA = 18 kJ mol-1, for Z to E isomerization in Ab670 was calculated. Interestingly, it agrees well with the one determined for a similar kind of transformation in stilbenes. Therefore, we found that dielectric spectroscopy can be a very useful technique to track Z to E interconversion in the highly viscous supercooled state. Consequently, a unique opportunity to follow this kind of isomerism at high pressures, high electric fields and under nanometric spatial confinement in pure supercooled compounds appeared.

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...

The mutarotation kinetics of pure molten D-fructose and its binary mixture with alcohols (i.e., sorbitol and maltitol) have been reported using Fourier Transform Infrared (FTIR), Broadband Dielectric Spectroscopy (BDS) and Density Functional Theory (DFT) calculations. The time evolution of the integrated intensity and structural relaxation time acts as a suitable dynamical observable to monitor the progress of the reaction in FTIR and BDS, respectively, leading to the construction of kinetic curves for the process. The bands at 776 cm−1 (νβ) and 990 cm−1 (να) indicate the respective vibrations originating from the β and α-isomers of D-fructose. The rate constants estimated from FTIR, (kIR) are shorter than those obtained from BDS, (kBDS) studies and the activation energies determined from both spectroscopies differ by more than 30 kJ mol−1. This is interpreted in the context of specific reaction pathways that contribute to the rate constants and drive mutarotation. Additionally, it is found that the rate of mutarotation depends on the system studied i.e., in binary mixtures consisting of sorbitol and D-fructose it becomes faster, while in solid dispersion with maltitol it gets slower. This fact can be explained by taking into account the viscosity of the system. In addition, natural bond orbital (NBO) calculations and an electrostatic potential surface (EPS) analysis were carried out to gain insight into the atomic charge distribution and description of the possible interactions between D-fructose and alcohol molecules. We note that there are some differences between both systems under examination in the strength of H-bonds. However, the impact of these interactions on the progress on mutarotation is not as significant as viscosity.

The molecular dynamics of three saccharides: D-glucose, 1,6-anhydro-D-glucose (levoglucosan) and 1,6:2,3-dianhydro-β-D-mannopyranose of various degrees of freedom, number of hydroxyl groups and internal structures was investigated over a wide range of temperatures and frequencies by means of Broadband Dielectric Spectroscopy (BDS). Despite the pronounced variety in the physicochemical properties of the carbohydrates, no change in the shape of the structural relaxation process was observed in the vicinity of the glass transition temperature (β(KWW) = 0.5). On the other hand further studies of the Debye-Stokes-Einstein relationship between dc conductivity and structural dynamics revealed some significant changes connected with the ability to form strong H-bonded structures. Moreover the presence of nearly constant loss (NCL) at moderate frequencies and just below the T(g) in the glassy state of levoglucosan and 1,6:2,3-dianhydro-β-D-mannopyranose was noticeable. We followed the temperature evolution of ε'' located at frequencies f = 0.1 kHz and f = 1 kHz, where the NCL is detected. Interestingly, a clear change in the dynamics far below the glass transition was observed in both compounds. This crossover (T(c)), found in different materials, and studied by various experimental techniques, is usually interpreted as being caused by the freezing of the Johari-Goldstein (JG) relaxation process. Alternatively it can also be due to the increasing anharmonicity in the density of vibrational states. Interestingly, it was shown that the slope of ε''(T) measured above the T(c) slightly changes while below the T(c) stays constant after physical aging. This is related to the densification of the sample that might result in steric hindrance and suppression of some kind of motion occurring in the glassy state, involving the larger parts of the molecules.

The aim of this work is to analyze in detail the effect of small hydrogen bonding (HB) structures and enantiomeric composition on the dynamics of glass-forming liquid ketoprofen. For that purpose dielectric relaxation, rheological and NMR studies were performed. Investigated samples are racemic ketoprofen, a single enantiomer of ketoprofen and a racemic ketoprofen methyl ester with no tendency to form HB dimers. The combination of complementary experimental techniques enables us to show that macroscopic viscosity η and α-relaxation time τα have nearly the same temperature dependencies, whereas the relation between the viscosity (or molecular reorientation) and the translational self-diffusion coefficient violates Stokes-Einstein law already at high temperature. Additionally, based on dielectric relaxation studies performed on increased pressure we were able to identify similarities and key differences in the supercooled liquid dynamics of investigated materials affected by their tendency to form intermolecular hydrogen bonds. This includes the effect of pressure on the glass transition temperature Tg, changes in the fragility parameter m and activation volume ΔV, the role of thermal energy and density fluctuations in governing the viscous liquid dynamics (Ev/Ep ratio). Finally, we have also demonstrated that the dynamic behaviour of a single enantiomer and the racemic mixture of the same compound are very much alike. Nevertheless, some slight differences were observed, particularly in the τα(T) dependencies measured in the vicinity of glass transition both at ambient and elevated pressure.

In this paper, we combine Broadband Dielectric Spectroscopy (BDS) at ambient and high pressure, and positron annihilation lifetime spectroscopy (PALS) data of 2-ethylhexanol in the bulk state and when infiltrated in native silica nanopores to elucidate the relative role of surface effects on the Debye and structural relaxation processes under 2D spatial constraints. We show that the two processes have different sensitivities to (i) the changes in density as quantified by the EV/Hp ratio and (ii) the degree of confinement. Significant enhancement of the dynamics of the confined molecules at low temperatures is related to the vitrification of the interfacial molecules (Tg,int) affecting the packing density of the core molecules. This is corroborated by the PALS measurements, which demonstrated that the effective volume for the confined samples is slightly higher and seems to be temperature invariant below Tg,int. Consequently, negative pressure systematically develops with lowering temperature reaching values of -100 and -110 MPa (depending on the pore size) at the glass transition temperature. This result offers a better understanding of the counterbalance between surface and finite size effects as well as the role of negative pressure in controlling the dynamics and the glass transition of liquids under 2D spatial restrictions.

In this paper, the kinetics of the radical polymerization of two monomeric ionic liquids: 1-ethyl- and 1-butyl-3-vinylimidazolium bis(trifluoromethanesulfonyl)imide ([evim][NTf2] and [bvim][NTf2], respectively) as well as the molecular dynamics of the obtained polymers were investigated by means of Broadband Dielectric Spectroscopy (BDS), Fourier Transform Infra-Red (FTIR) spectroscopy and Differential Scanning Calorimetry (DSC). We propose a novel method of dielectric data analysis, to extract information on the progress of polymerization in highly conductive materials. It was found that the progress of reaction can be easily monitored by measuring the time evolution of dc conductivity, which correlates very well with the monomer conversion estimated from calorimetric or FTIR investigations. Additionally, it is clearly shown that even a small modification in the chemical structure, i.e. the length of the alkyl substituent, of monomeric ionic liquids leads to a dramatic change in the properties of the produced polymers. The obtained results are discussed in light of recent studies indicating a completely different tendency to nanostructure ordering in the investigated monomeric ionic liquids.

Some molecular glass-formers can crystallize in the glassy state, some of which are van der Waals molecules and some are pharmaceuticals. The molecular mechanism responsible for this glass-to-crystal mode of crystallization is of interest to the glass transition research community as well as to the pharmaceutical industry because the effect is detrimental to stability of amorphous form of the drugs stored below the glass transition temperature. Two prominent models have been proposed for the molecular mechanism. In the homogeneous nucleation-based crystallization model, the molecular mechanism is the secondary relaxation, and the other model assumes that the molecular process responsible for crystal growth in the glassy state is from the local molecular motions. Crystal growth requires motion of the entire molecule, and in the glassy state the only such local molecular motion is engendered by the secondary relaxation of the Johari-Goldstein (JG) kind. While the JG secondary relaxation is the crux in the two models of glass-to-crystal growth, it has not been found in the glassy state of the pharmaceuticals studied so far. The examples include 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY), indomethacin (IMC) and nifedipine (NIF). In the absence of any evidence of the JG secondary relaxation, the conundrum is that the two models of glass-to-crystal growth cannot be validated. It turns out these pharmaceuticals all have structural α-relaxations with narrow frequency dispersion. Empirically, glass-formers with narrow α-dispersion have JG secondary relaxation with weak relaxation strength, not well separated from the α-relaxation, and hence cannot be resolved. Theoretically, the narrow width of the α-dispersion is due to weak intermolecular coupling. In this article we enhance the intermolecular coupling of NIF by mixing with octaacetylmaltose to enhance the intermolecular coupling of NIF. In this way we have successfully resolved the JG secondary relaxation in the dielectric loss spectra of the NIF component in the glassy state, and validated the two models of glass-to-crystal growth.

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...

Fourier Transform Infrared and Broadband Dielectric Spectroscopies were applied to follow kinetics as well as molecular dynamics upon step-growth polymerization of bisphenol-A diglycidyl ether (DGEBA) with aniline both in bulk and in anodic aluminum oxide (AAO) membranes. For the first time the dynamics and kinetics of a curing epoxy system under confinement were analyzed and compared with the reaction in the bulk. As it turned out, polymerization is faster under confinement, compared to the analogous reaction carried out in the bulk system at the same temperature conditions. Additionally, the reaction speeds up with the degree of confinement. Furthermore, it was found that the initial step of the polymerization is significantly reduced or even suppressed in nanochannels; this is evident from the observation that kinetic curves do not follow sigmoidal shape that is characteristic for the autocatalytic type of chemical reactions. FTIR data showed unquestionably that the rate of reaction is slower at the surface of the pores with respect to the polymerization at the core of nanochannels. This finding is in tandem with Monte Carlo simulation reporting lower reactivity of the functional units close to the pore walls. Moreover, we found out that the activation barrier for the polymerization remains unchanged under confinement. Finally, dielectric measurements revealed that there is a characteristic change in the slope of segmental relaxation times plotted as a function of the time of reaction under confinement, a phenomenon whose comprehension demands further investigation.

Kinetics and dynamics of the curing of bisphenol-A diglycidyl ether (DGEBA) with various agents i.e. cyclohexylamine, aniline and 2-ethylhexylamine, were investigated by means of Broadband Dielectric Spectroscopy (BDS) over a wide range of thermodynamic conditions. We proposed a novel method of dielectric data analysis to extract information on the progress of the curing reaction. This approach was validated by complementary calorimetry measurements. High pressure studies indicated that compression significantly reduces the time of the reaction. At the same time, a decrease in monomer conversion and the glass transition temperature of the recovered product was observed. This was due to vitrification of the system that occurs in a relatively short time. We found a linear correspondence between the time of the polymerization after which the investigated system undergoes glass transition and the degree of monomer conversion. Additionally, activation volumes for the investigated reactions were determined and found to lie in the range −18 and −38 cm3 mol−1. The calculated values are lower than ΔV estimated for the ring opening reaction provided in the literature. However our data unquestionably showed that this quantity depends strongly on both the chemical structure of the substrates as well as thermodynamic conditions.

In this paper, Broadband Dielectric Spectroscopy (BDS) has been applied to study the molecular dynamics of the two active pharmaceutical ingredients (APIs), probucol (PRO) and droperidol (DRO), above and below the glass transition temperature, at varying thermodynamic conditions. We found that the structural (α)-relaxation process in both compounds is sensitive to compression. It was reflected in the high pressure coefficients of the glass transition temperature, dTg/dp = 227 K/GPa and dTg/dp = 427 K/GPa for DRO and PRO, respectively. In this context, it is worthwhile to emphasize that dTg/dp calculated for the latter API is the highest reported to date for the low molecular weight glass formers. Furthermore, the data collected upon squeezing samples revealed that the pressure dependence of the relaxation times of the Johari Goldstein (JG) β-process in PRO is weaker with respect to that of structural relaxation. Thus, a breakdown of exact superposition of both modes has been noted. A slightly different scenario was observed in DRO, where relaxation times of the secondary non-JG γ-process, obtained at different T and p, plotted versus Tg/T, collapsed forming a single curve. A breakdown of exact isochronal superpositioning of α- and JG β-relaxation times at varying thermodynamic conditions in PRO, that is weakly H-bonded low molecular weight glass former, is in accordance with the data reported for the strongly associating compounds (e.g., sorbitol). Moreover, recently a similar scenario has been observed for some polymers, i.e., 1,4-polybutadiene (PBD) (Ransom et al., 2018), poly(methyl methacrylate) (PMMA) (Casalini and Roland, 2013) and polyisoprene (PI) (Kolodziej et al., 2018). This phenomenon, which is consistent with the approximate invariance of the ratio of these two relaxation times to change of thermodynamics conditions (as predicted by the Coupling Model), was assigned to the increasing torsional rigidity of the macromolecule backbone or alternatively to the non-uniform responses to variations of temperature and pressure of the distributed modes composing the JG β-process, resulting in changes of the spectral shape and different fβ(p,T) obtained from the fitting procedure. One can suppose that due to the variation in the population of weak H-bonds at elevated pressure in PRO, the latter effect might be enhanced, contributing to the observed experimental finding. Finally, the data reported herein emphasize the impact of molecular aspects related to specific interactions on the correlation between α- and JG β-relaxation at varying T and p conditions.

In this paper, we studied the impact of saccharides having a similar backbone but differing in the degree of freedom, local molecular mobility, flexibility of the ring and intermolecular interactions on the glass-forming ability (GFA) of naproxen (NAP) in binary mixtures. For this purpose, a series of methyl and acetyl derivatives of glucose (GLS) and anhydroglucose (anhGLS), as well as neat anhGLS have been used to produce homogeneous solid dispersions (SDs) of varying molar concentration of examined active pharmaceutical ingredient (API). Systematic measurements with the use of Differential Scanning Calorimetry (DSC) and Broadband Dielectric Spectroscopy (BDS) enabled us to determine the phase transitions, homogeneity and molecular mobility of the investigated binary mixtures as well as the impact of excipient on the crystallization tendency of NAP. It turned out that acetylated glucose (acGLS), one of the most mobile and flexible saccharides of all examined herein materials, is the best excipient enhancing the GFA of studied API. Although, it should be noted that upon storage at room temperature, we observed the recrystallization of NAP from binary mixtures. Interestingly, API always crystallized to the initial polymorphic form, as shown by X-ray diffraction (XRD) investigations. Finally, since additional measurements with the use of Fourier Transform Infrared (FTIR) Spectroscopy clearly indicated that there are no significant differences in the intermolecular interactions in the systems composed of NAP and all examined saccharides, one can postulate that the mobility and ring flexibility of the matrix have, , the most important impact on the crystallization tendency of NAP upon cooling. Consequently, it seems that in some cases, more mobile/flexible matrices can be a much better choice to enhance the glass-forming ability of studied pharmaceutical.

Currently, a great effort is put on the understanding of the effect of the nanometrical constraint on the dynamics of the soft materials. Recent studies by Alexandris et al. [Macromolecules, 2016, 49, 7400–7414] and some of us [J. Phys. Chem. C, 2019, 123, 5549–5556] revealed that the enhancement of the molecular mobility and depression in the glass transition of various low and high molecular weight glass formers infiltrated into Anodic Aluminum Oxide (AAO) templates strongly correlates with the strength of the interfacial interactions between the materials and the porous medium. However, in those investigations, one very important and fundamental aspect related to the variation in the wettability, the surface tension as well as the interfacial energy due to surface curvature has been completely overlooked. Herein, we have performed systematic and unique Atomic Force Microscopy (AFM) measurements on the model glass-forming liquid, glycerol (GLY), incorporated into porous AAO membranes of varying pore diameter. It was found that with increasing degree of confinement, the adhesion force between GLY and AFM tip decreases significantly. It seems that as indicated by the Tolman relation, the interfacial tension of the confined GLY drops leading to a better wetting of polyalcohol within the smallest pores. Interestingly, for this particular system (confined within templates of d = 10 nm), a complementary Differential Scanning Calorimetry (DSC) investigations revealed the presence of the two glass transition temperatures upon heating runs. This indicated that the enhancement of the interactions between alumina and alcohol leads to the formation of the interfacial layer that vitrifies at higher temperature (Tg,interfacial) than the bulk material. Interestingly, the observed double Tgs appeared only on heating. Moreover, different thermal protocols revealed the variation of the heat capacity jump corresponding to the glass transition temperature of the interfacial layer upon the annealing experiments, indicating the ongoing desorption process. In addition, it was also found that the structural dynamics of GLY incorporated within d = 10 nm starts to deviate below Tg,interfacial from the behavior of the non-confined sample. Reported data are the first experimental evidence on the correlation between variation of the surface interactions with the substrate's curvature and enhancement of the dynamics of the confined liquids. Thus, a better understanding of the dynamics of confined soft matter, especially the relation between the finite size and surface interactions can be gained.

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.

Broadband dielectric and Fourier transform infrared spectroscopies were applied to study dynamics and kinetics upon polymerization of bisphenol A diglycidyl ether (DGEBA) and 2-ethylhexylamine under different thermodynamic conditions. We found out that polymerization constant rates as well as activation barriers determined from both methods are almost the same (within the experimental uncertainty). High pressure studies have enabled to calculate the activation volume which was found ΔV = −38 cm3/mol and −46 cm3/mol in the limit of low pressure for two independent isothermal experiments. This finding shows that the activation volume is not constant, but varies with thermodynamic conditions. As a result, polymerization reaction cannot be described with the use of only one given activation volume, as it is usually reported in literature. It should be also noted that ΔV increases with compression and tends to be positive above P = 430 and 370 MPa for the reaction carried out at T = 293 K and T = 313 K, respec...

High pressure polymerization of glycidol was carried out at four different pressures ranging from p = 0.1 MPa up to p = 800 MPa at room temperature ( T = 298 K). To monitor polymerization kinetics at high pressure dielectric spectroscopy was employed. Constant rates of polymerization at given thermodynamic conditions were determined form the analysis of dc conductivity as well as variation of the static dielectric permittivity. To be sure that both quantities can be used to monitor progress of the polymerization reaction, complementary FTIR studies were carried out at ambient pressure. The vibration of the C–O–C epoxy rings assigned to the band in the 760–880 cm −1 range was chosen to follow progress of the monomer conversion. The rate constant “ k ” determined from the Fourier Transform Infrared data analysis, was found to be in good correlation with dielectric data. Furthermore, having rate constant obtained for polymerization carried out at different pressures and constant temperature the activation volume was determined ΔV = −3 cm 3 /mol. Finally, analysis with the use of MALDI-TOF 2 MS 2 equipment showed that high pressure favors formation of polymers of greater molecular weight. Moreover, it was found that mechanism of polymerization at high pressure is quite different with respect to the reaction carried out at ambient pressure. It turned out that side reaction occurring upon polymerization of glycidol are completely eliminated at high compression.

The uniform thin films with variable thicknesses (d = 49, 120, 220 nm) of active pharmaceutical ingredient (API) glibenclamide (GCM) was spin-coated and investigated using broadband dielectric, grazing incident FTIR spectroscopies, atomic force microscopy, and ellipsometry. Data analysis revealed that nanoconfined systems consist of a mixture of amide and imidic acid forms of this pharmaceutical, wherein the ratios of both tautomeric forms in the thin films were different with respect to the molten supercooled bulk system. Moreover, changes in the populations of glibenclamide tautomers, i.e. higher amide to imides ratio in the spatially restricted API with respect to the bulk sample, had a strong impact on the character of the proton transfer reaction. In this context, the kinetic curves constructed on the base of infrared data for the bulk system follow the sigmoidal shape, characteristic for the autocatalytic reaction, while results obtained for the confined samples provide exponential character and indicate first-order transformation. This allows hypothesizing that the autocatalytic nature of the tautomerism in the bulk sample is most likely related to the formation of the amide tautomers which further catalyze the progress of imide-amide transformation. Our results are the first studies showing that the change in the thickness of the film may affect the properties and isomerization kinetics in a pharmaceutical systems. Finally, our data open a new perspective for developing new drug delivery systems.

Broadband Dielectric Spectroscopy (BDS) is used to study the molecular dynamics of thin layers of itraconazole – an active pharmaceutical ingredient with rod-like structure and whose Differential Scanning Calorimetry (DSC) scans reveal liquid crystalline-like phase transitions. It is found that (i) the structural relaxation process remains bulk like, within the limits of experimental accuracy, in its mean relaxation rate, while (ii) its shape is governed by two competing events: interfacial interactions, and crystalline ordering. Additionally, (iii) the dynamics of the d-relaxation - assigned to the flip-flop rotation of the molecule about its short axis - deviates from bulk behaviour as the glass transition is approached for the confined material. These observations are rationalized within the framework of molecular dynamics as currently understood.

This paper presents comprehensive studies on the molecular dynamics of a pharmaceutically important substance, posaconazole. In order to characterize relaxation dynamics in the supercooled liquid and glassy states, dielectric and mechanical spectroscopies were applied. Dielectric data have indicated multiple relaxation processes that appear above and below the glass transition temperature Tg (τα=100 s) of posaconazole. From the curvature of the dielectric log10(τα) versus inverse of temperature dependence, we determine so-called "fragility", being a very popular parameter for classifying the structural dynamics of supercooled liquids and polymers. From the calculations, we get m=150, which means that is one of the most fragile glass-forming liquids. In this paper, the relaxation dynamics of supercooled posaconazole extracted from the dielectric response function was also confronted with shear-mechanical relaxation. Finally, we have also presented a direct comparison of the fragility and the number of dynamically correlated molecules Nc determined from dynamic calorimetry curves and dielectric and mechanical spectroscopies, showing a clear deviation in the picture of glass-transition dynamics generated by calorimetric and spectroscopic techniques.

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).

In this letter, we reported thorough the structural and molecular dynamics studies on 1,6-anhydro-β-D-glucose, the second compound reported so far that is capable to form rotator and supercooled liquid phases. In contrast to the data presented for ethanol, temperature dependences of structural dynamics in both phases are very comparable. On the other hand, X ray measurements revealed unusually long range ordering/correlations between molecules in the ODIC (d ≈ 95 Å) and supercooled phases (d ≈ 30–40 Å) of this carbohydrate. Our consideration clearly demonstrated that the interplay between length scales of static range ordering and dynamical heterogeneities as well as internal molecular arrangement seem to be the key to understanding the molecular dynamics of different materials characterized by varying degree of disorder in the vicinity of the glass transition temperature.

The properties of a molecular liquid confined at the nanometer length scale can be very distinct from the bulk. For that reason, the macro- and the nanoscopic behaviors of glass-forming liquids are regarded as two nonconnected realms, governed by their own rules. Here, we show that the glassy dynamics in molecular liquids confined to nanometer pores might obey the density scaling relation, ργ/T, just like in bulk fluids. Even more surprisingly, the same value of the scaling exponent γ superposes the α-relaxation time measured at different state points in nanoscale confinement and upon increased pressure. We report this remarkable finding for van der Waals liquids tetramethyl-tetraphenyl-trisiloxane (DC704) and polyphenyl ether (5PPE), considered as simple, single-parameter liquids. Demonstrating that the density scaling idea can be fulfilled in both environments opens an exciting possibility to predict the dynamic features of the nanoconfined system close to its glass-transition temperature from the high-...

Broadband dielectric spectroscopy (BDS) and differential scanning calorimetry (DSC) have been employed to probe dynamics and charge transport of 1-butyl-3-vinylimidazolium bis(trifluoromethanesulfonyl)imide ([bvim][NTf2]) confined in native uniaxial AAO pores as well as to study kinetics of radical polymerization of the examined compound as a function of the degree of confinement. Subsequently, the electronic conductivity of the produced polymers was investigated. As observed, polymerization carried out at T = 363 K proceeds faster under confinement with some saturation effect observed for the sample in pores of smaller diameter. Obtained results were discussed in the context of the very recent reports showing that the free volume of the confined material is higher with respect to the bulk one. It was also noted that conductivity of poly[bvim][NTf2] is significantly higher with respect to the macromolecules obtained upon bulk polymerization. Moreover, charge transport of the confined macromolecules is eve...

Broadband dielectric spectroscopy (BDS) and differential scanning calorimetry (DSC) were applied to investigate the molecular dynamics and phase transitions in binary mixtures composed of naproxen (NAP) and acetylated saccharides: maltose (acMAL) and sucrose (acSUC). Moreover, the application of BDS method and optical microscopy enabled us to study both crystallization kinetics and crystal growth of naproxen from the solid dispersions with the highest content of modified carbohydrates (1:5wt ratio). It was found that the activation barriers of crystallization estimated from dielectric measurements are completely different for both studied herein mixtures. Much higher Ea (=205kJ/mol) was obtained for NAP-acMAL solid dispersion. It is probably due to simultaneous crystallization of both components of the mixture. On the other hand, lower value of Ea in the case of NAP-acSUC solid dispersion (81kJ/mol) indicated, that naproxen is the only crystallizing compound. This hypothesis was confirmed by X-ray diffraction studies. We also suggested that specific intermolecular dipole-dipole interactions between active substance and excipient may be an alternative explanation for the difference between activation barrier obtained for NAP-acMAL and NAP-acSUC binary mixtures. Furthermore, optical measurements showed that the activation energy for crystal growth of naproxen increases in binary mixtures. They also revealed that both excipients: acMAL and acSUC move the temperature of the maximum of crystal growth towards lower temperatures. Interestingly, this maximum occurs for nearly the same structural relaxation time, which is a good approximation of viscosity, for all samples. Finally, it was also noticed that although naproxen crystallizes to the same polymorphic form in both systems, there are some differences in morphology of obtained crystals. Thus, the observed behavior may have a significant impact on the bioavailability and dissolution rate of API produced in that way.

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.

Antibiotics are chemical compounds of extremely important medical role. Their history can be traced back more than one hundred years. Despite the passing time and significant progress made in pharmacy and medicine, treatment of many bacterial infections without antibiotics would be completely impossible. This makes them particularly unique substances and explains the unflagging popularity of antibiotics within the medical community. Herein, using dielectric spectroscopy we have studied the molecular mobility in the supercooled liquid and glassy states of three well-known antibiotic agents: azithromycin, clarithromycin and roxithromycin. Dielectric studies revealed a number of relaxation processes of different molecular origin. Besides the primary α-relaxation, observed above the respective glass transition temperatures of antibiotics, two secondary relaxations in the glassy state were identified. Interestingly, the fragility index as well as activation energies of the secondary processes turned out to be practically the same for all three compounds, indicating probably much the same molecular dynamics. Long-term stability of amorphous antibiotics at room temperature was confirmed by X-ray diffraction technique, and calorimetric studies were performed to evaluate the basic thermodynamic parameters. Finally, we have also checked the experimental solubility advantages given by the amorphous form of the examined antibiotics.

In this paper, the molecular dynamics of a series of ester derivatives of ibuprofen (IBU), in which the hydrogen atom from the hydroxyl group was substituted by the methyl, isopropyl, hexyl, and benzyl moieties, has been investigated using Broadband dielectric (BD), Nuclear magnetic resonance (NMR), and Raman spectroscopies. We found that except for benzyl IBU (Ben-IBU), an additional process (slow mode, SM) appears in dielectric spectra in all examined compounds. It is worth noting that this relaxation process was observed for the first time in non-modified IBU (a Debye relaxation). According to suggestions by Affouard and Correia [J. Phys. Chem. B. 114, 11397 (2010)] as well as further studies by Adrjanowicz et al. [J. Chem. Phys. 139, 111103 (2013)] on Met-IBU, it was attributed to synperiplanar-antiperiplanar conformational changes within the molecule. Herein, we have shown that with an increasing molecular weight of the substituent, the relaxation times of the SM become longer and its activation energy significantly increases. Moreover, this new relaxation mode was found to be broader than a simple Debye relaxation in Iso-IBU and Hex-IBU. Additional complementary NMR studies indicated that either there is a significant slowdown of the rotation around the O=C-O-R moiety or this kind of movement is completely suppressed in the case of Ben-IBU. Therefore, the SM is not observed in the dielectric loss spectra of this compound. Finally, we carried out isothermal experiments on the samples which have a different thermal history. Interestingly, it turned out that the relaxation times of the structural processes are slightly shorter with respect to those obtained from temperature dependent measurements. This effect was the most prominent in the case of Hex-IBU, while for Ben-IBU, it was not observed at all. Additional time-dependent measurements revealed the ongoing equilibration manifested by the continuous shift of the structural process, until it finally reached its equilibrium position. Further Raman investigations showed that this effect may be related to the rotational/conformational equilibration of the long hexyl chains. Our results are the first ones demonstrating that the structural process is sensitive to the conformational equilibration occurring in the specific highly viscous systems.

Broadband Dielectric Spectroscopy was applied to investigate molecular dynamics of two anhydrosaccharides, i.e., 1,6-anhydro-β-D-mannopyranose, anhMAN (hydrogen-bonded system) and 2,3,4-tri-O-acetyl-1,6-anhydro-β-D-glucopyranose, ac-anhGLU (van der Waals material), at different thermodynamic conditions. Moreover, the reported data were compared with those recently published for two other H-bonded systems, i.e., 1,6-anhydro-β-D-glucopyranose (anhGLU) and D-glucose (D-GLU). A direct comparison of the dynamical behavior of the materials with a similar chemical structure but significantly differing by the degrees of freedom, complexity, and intermolecular interactions made it possible to probe the impact of compression on the fragility, Temperature-Pressure Superpositioning and pressure coefficient of the glassy crystal/glass transition temperatures (dTgc/dp ; dTg/dp). Moreover, the correlation between dTgc/dp determined experimentally from the high-pressure dielectric data and the Ehrenfest equation has been tested for the plastic crystals (anhGLU and anhMAN) for the first time. Interestingly, a satisfactory agreement was found between both approaches. It is a quite intriguing finding which can be rationalized by the fact that the studied materials are characterized by the low complexity (lower degrees of freedom with respect to the molecular mobility) as well as ordered internal structure. Therefore, one can speculate that in contrast to the ordinary glasses the dynamics of the plastic crystals might be described with the use of a single order parameter. However, to confirm this thesis further, pressure-volume-temperature (PVT) experiments enabling calculations of the Prigogine Defay ratio are required.

High pressure dielectric studies on the H-bonded liquid D-glucose and Orientationally Disordered Crystal (ODIC) 1,6-anhydro-D-glucose (levoglucosan) were carried out. It was shown that in both compounds, the structural relaxation is weakly sensitive to compression. It is well reflected in the low pressure coefficient of the glass transition and orientational glass transition temperatures which is equal to 60 K/GPa for both D-glucose and 1,6-anhydro-D-glucose. Although it should be noted that ∂Tg(0)/∂p evaluated for the latter compound seems to be enormously high with respect to other systems forming ODIC phase. We also found that the shape of the α-loss peak stays constant for the given relaxation time independently on the thermodynamic condition. Consequently, the Time Temperature Pressure (TTP) rule is satisfied. This experimental finding seems to be quite intriguing since the TTP rule was shown to work well in the van der Waals liquids, while in the strongly associating compounds, it is very often violated. We have also demonstrated that the sensitivity of the structural relaxation process to the temperature change measured by the steepness index (mp) drops with pressure. Interestingly, this change is much more significant in the case of D-glucose with respect to levoglucosan, where the fragility changes only slightly with compression. Finally, kinetics of ODIC-crystal phase transition was studied at high compression. It is worth mentioning that in the recent paper, Tombari and Johari [J. Chem. Phys. 142, 104501 (2015)] have shown that ODIC phase in 1,6-anhydro-D-glucose is stable in the wide range of temperatures and there is no tendency to form more ordered phase at ambient pressure. On the other hand, our isochronal measurements performed at varying thermodynamic conditions indicated unquestionably that the application of pressure favors solid (ODIC)-solid (crystal) transition in 1,6-anhydro-D-glucose. This result mimics the impact of pressure on the crystallization of fully disordered supercooled van der Waals liquids.

Molecular dynamics of pure nifedipine and its solid dispersions with modified carbohydrates as well as the crystallization kinetics of active pharmaceutical ingredient (API) above and below the glass transition temperature were studied in detail by means of broadband dielectric spectroscopy (BDS), differential scanning calorimetry (DSC), and X-ray diffraction method. It was found that the activation barrier of crystallization increases in molecular dispersions composed of acetylated disaccharides, whereas it slightly decreases in those consisting of modified monocarbohydrates for the experiments carried out above the glass transition temperature. As shown by molecular dynamics simulations it can be related to the strength, character, and structure of intermolecular interactions between API and saccharides, which vary dependently on the excipient. Long-term physical stability studies showed that, in solid dispersions consisting of acetylated maltose and acetylated sucrose, the crystallization of nifedipine is dramatically slowed down, although it is still observable for a low concentration of excipients. With increasing content of modified carbohydrates, the crystallization of API becomes completely suppressed. This is most likely due to additional barriers relating to the intermolecular interactions and diffusion of nifedipine that must be overcome to trigger the crystallization process.