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This article investigated the effect of shear strain on the nematic itraconazole (ITR) from both elastic and plastic deformation regions. The rheo-dielectric technique was used for this purpose. It has been demonstrated that shear strain can change the sample color, liquid crystal alignment as well as its dielectric and thermal properties. The observed modifications depend on the shear strain value. One can distinguish four regions regarding the slope of ITR stress–strain dependence and caused changes. Proper alignment changes (obtained after the shearing procedure) can additionally affect the further recrystallization of ITR to other than the initial, i.e., second polymorphic form. [Display omitted] [ABSTRACT FROM AUTHOR]

The conduction mechanism of polymer nano-composite electrolytes are studied using broadband dielectric spectroscopy over a wide range of frequency and temperature. The polymer nano-composites consisting of polyethylene oxide as polymer host, lithium trifluoromethanesulfonate as salt, and nano-crystalline zirconia as filler are prepared using solution casting method. Formation of polymer salt complex and nano-composites are confirmed from x-ray diffraction studies. The electrical conductivity and relaxation phenomena of the polymer salt complex as well as the composites are studied using broadband dielectric spectroscopy. At room temperature, the dc conductivity of the polymer nano-composites are found higher by two orders of magnitude than that of corresponding polymer salt complex. Temperature dependence of dc conductivity is following Vogel-Tamman-Fulcher trend, suggesting strong coupling between ionic conductivity and segmental relaxation in polymer electrolytes. Relaxation phenomena are studied with dielectric and modulus formalism. Frequency dependent ac conductivity show universal dielectric response and nearly constant loss features at high and low temperature regions respectively. The origin of universal dielectric response and nearly constant loss are analysed and discussed using different approaches. Kramer - Krönig approach suggests the origin of nearly constant loss is due to caged ion dynamics feature. [ABSTRACT FROM AUTHOR]

In recent years, there is a growing interest in improving the physicochemical stability of amorphous pharmaceutical solids due to their very promising applications to manufacture medicines characterized by a better water solubility, and consequently by a higher dissolution rate than those of their crystalline counterparts. In this review article, we show that the molecular mobility investigated both in the supercooled liquid and glassy states is the crucial factor required to understand molecular mechanisms that govern the physical stability of amorphous drugs. We demonstrate that pharmaceuticals can be thoroughly examined by means of the broadband dielectric spectroscopy, which is a very useful experimental technique to explore different relaxation processes and crystallization kinetics as well. Such studies conducted in the wide temperature and pressure ranges provide data needed in searching correlations between properties of molecular dynamics and crystallization process, which are aimed at developing effective and efficient methods for stabilizing amorphous drugs. [ABSTRACT FROM AUTHOR]

In this paper, we studied for the first time the impact of the molecular weight, M n , and the topology on the molecular dynamics of a series of grafted poly(poly(dimethylsiloxane methacrylate)) (polyPDMSMA). The behavior of grafted (molecular brushes) polyPDMSMA and their three-armed counterparts of tailor-made properties prepared by Atom Transfer Radical Polymerization (ATRP) was monitored by means of broadband dielectric spectroscopy (BDS), differential scanning calorimetry (DSC) and comprehensive rheology analysis. Surprisingly, the dielectric loss spectra of all studied polyPDMSMA exhibit the presence of two dielectric relaxation processes above their glass transition temperature, T g. A comparison of dielectric, calorimetric and mechanical data indicated that the faster and slower relaxation processes identified in loss spectra can be related to the segmental and chain dynamics, respectively. Interestingly, we observed that the "local" segmental dynamics of studied polyPDMSMA, involving the mobility of few repeatable units creating a segment, is almost unaffected by neither the length of polymer chain, number of grafts nor its topology. This is also reflected in a weak molecular weight-dependences of T g of studied polyPDMSMA independently to their topology. On the other hand, the time-scale separation between segmental and the chain modes as well as the amplitude of the latter process increase with growing M n of all examined polyPDMSMA. Additionally, it should be mentioned that the mechanical data collected for samples characterized by high molecular weight (of M n > 280 kg/mol) reveal the emergence of additional process (most likely related to the grafts and/or the star arm relaxation) at the intermediate regime, independently to their topology. Interestingly, this mode was observed to be much slower for the star-shaped macromolecules when compared to the grafted polymers, despite their lower M n. This implies that the observed differences are not a result of different molecular weights, but rather originate from a various molecular mechanism due to the different topology of the studied samples. In this context, one can assume that in the case of high-molecular-weight macromolecules, the backbone architecture has a significant influence on the behavior of polymers, including their molecular dynamics. [Display omitted] • Increase of the glass transition of studied polyPDMSMA with their molecular weight. • Loss spectra of polyPDMSMA exhibit multiple dielectric relaxation processes. • Observed dielectric processes were assigned as the chain and segmental modes. • Presence of grafts/arms relaxation (or entanglement segments) in mechanical data. [ABSTRACT FROM AUTHOR]

Different experimental techniques were applied to study thermal and structural properties, strength of H-bonds, possible keto - enol tautomerism and molecular dynamics at various thermodynamic conditions in the H-bonded active substance, curcumin (CRM). Dielectric measurements revealed dynamical features of examined compound that are uncharacteristic for the associated systems. This includes enormously large pressure coefficient of the glass transition temperature and prominent drop of the fragility with compression. Simultaneously, the shape of α -process slightly broadened at elevated pressures. Infrared investigations demonstrated that this effect is related to the variation in the population of H-bonds. Moreover, we studied the changes in the structural and dynamical properties of the glasses prepared upon cooling of the melt (ordinary glass, OG) and the one obtained after compression of CRM in the liquid phase and decompression at T = 293 K (dense glass, DG). Interestingly, during the aging of the latter sample, a clear shift of the β -relaxation towards higher frequencies was noted. This unexpected result indicated that the density of DG is probably getting smaller with time. Complementary X-ray diffraction experiments confirmed this supposition. Additionally, they showed that in DG there are traces of polymorph II of CRM that has a higher density than initial crystals (polymorph I). Finally, infrared studies demonstrated that H-bond pattern in DG is slightly different with respect to OG. Furthermore, Raman investigations suggested that probably keto - enol tautomerism might be shifted towards diketo form in the glass obtained at high compression. Our investigations are very interesting in the context of better understanding of the behavior of associated systems at high compression as well as provide a better insight into dynamics of higher density glasses produced at elevated pressures. Unlabelled Image [ABSTRACT FROM AUTHOR]

In this paper, the high-pressure calorimetry was used to monitor the heat of the polymerization of bisphenol-A diglycidyl ether (DGEBA) mixed with a stoichiometric amount of aniline over a wide range of pressure (p = 0.1–350 MPa at T = 298.15 K). To the best of our knowledge, this is the first high-pressure calorimetric study of the reaction kinetics of the epoxy resin curing processes. The collected novel experimental data were analysed with two models: the original Kamal and its modified version taking into account the real monomer conversion, which provides insight into the progress of two subsequent non-catalyzed and catalyzed reactions occurring during the step growth polymerization. It was found that the determined rate constants are sensitive to pressure and model dependent, resulting in different activation volumes, which fall within the range from −16 cm3/mol to −26 cm3/mol. Interestingly, these values are similar to those reported for the epoxide ring-opening polymerization reaction, which changes in the range between −15 cm3/mol to −20 cm3/mol. In addition, the analysis of the high-pressure data revealed that the original Kamal model fails to describe kinetic curves obtained for the polymerization reaction, where the monomer conversion is far below 100%. Interestingly, such effects are considered to be due to the change in the mechanism of the reaction from mass to the diffusion-controlled regime. Here, we explicitly have shown that it has nothing to do with this phenomenon since after considering solely the real monomer conversion in the Kamal model fits, quality has been significantly improved. As a consequence, estimated rate constants are more reliable. Results presented herein clearly indicated that high-pressure experiments provide a new perspective to understand the progress of the classical reactions, as step-growth polymerization that has mainly been studied as a function of the chemical composition and temperature. Image 1 - High-pressure calorimetric data for step-growth polymerization (SGP) are presented - Original Kamal and modified version considering the monomer conversion were tested - Original model fails if the real monomer conversion is far below 100% - Rate constants are sensitive to pressure and model dependent - Activation volumes of catalyzed and non-catalyzed reactions in SGP are different [ABSTRACT FROM AUTHOR]

Highlights • There are marked differences in dynamics of modified linear and cyclic carbohydrates. • A variation in the distribution of τ α between linear and cyclic compounds is observed. • The evolutions of the T g and m versus M w in both groups of materials are different. • The shape of the α -process in saccharides of the same topology doesn't change with M w. Abstract In this paper, the molecular dynamics and thermal properties of representative acetylated linear and cyclic oligosaccharides: acTRE, acRAF, acSTA, ac-α-CD, ac-β-CD, ac-γ-CD, have been investigated by using broadband dielectric spectroscopy and differential scanning calorimetry. We found that there are marked differences in the dynamics of the structural and secondary relaxation processes in both groups of materials. Just to mention a variation in the distribution of the structural relaxation times as well as different evolutions of the glass transition temperature (T g) and fragility (m) versus molecular weight (M w), which seem to be affected by the shape of the molecule, strain in the carbohydrate ring and mobility of side acetyl moieties. [ABSTRACT FROM AUTHOR]

The anticancer drug bicalutamide was co-milled with either Macrogol 6000 or Poloxamer 407, and the physicochemical parameters that drive the phase transition of binary systems and influence the dissolution modification of bicalutamide were studied. Milled binary systems with reduced particle size were assessed by scanning electron microscopy and laser diffraction measurements. The results of thermal analysis supported by X-ray diffractometry confirmed the reduction of the crystallinity of bicalutamide co-milled with Macrogol 6000. Infrared spectroscopy was used to determine the molecular structure of the samples and indicated weak interactions between drug and polymer molecules. Two mechanisms were identified and were involved in up to 11-fold enhanced dissolution. The first one was based on improved wettability due to a decreased contact angle in samples containing Macrogol 6000. The second one relied on the solubilization of bicalutamide within nanoaggregates formed by Poloxamer 407 that resulted from its surface activity. This finding was confirmed with fluorescence spectroscopy, dynamic light scattering and cryogenic transmission electron microscopy assays. Given the dissolution rate-limited absorption combined with the reduced bioavailability of bicalutamide as a BCS class II drug, the assessment of the mechanisms driving the increase in drug dissolution is of particular importance in drug development. [ABSTRACT FROM AUTHOR]

The synthesis of poly(ionic liquid)s (PILs), a new class of polymers with numerous possible applications and tailored thermorheological properties, is quite a challenging task. To achieve that goal, different strategies have been proposed and developed. However, in the majority of cases macromolecules with relatively low molecular weights and high dispersities were produced, probably due to the strong intermolecular coulombic interactions that determine the behavior of monomeric ionic liquids. In this paper, we proposed a completely new approach that relies on the pressure-induced reversible addition fragmentation chain transfer polymerization (RAFT) to produce PILs of desired properties. For this purpose, a series of model imidazolium-based ionic monomers, with different lengths of aliphatic side chains as additional steric hindrances, have been successfully polymerized under high pressure (p = 250, 500 and 800 MPa). In contrast to results obtained at ambient pressure, all monomers yielded high molecular weight polymers (degrees of polymerization DP n  ≤ 10 000) with narrow dispersities (Ð∼1.10). From the kinetic data obtained at various thermodynamic conditions, the rate of polymerization, R p , and overall activation volumes, ΔV, were estimated, which in the limit of low pressures varied as follows −16.7, −18.1, −32.6 and −35.6 cm mol −1 for [MVIM][NTf 2 ], [EVIM][NTf 2 ], [BVIM][NTf 2 ] and [OVIM][NTf 2 ], respectively. An unexpected significant jump in ΔV can be correlated with the nanostructure organization that, accordingly to the literature, starts to dominate in the latter two monomers. It was also demonstrated that below p = 500 MPa, the termination reaction is almost completely suppressed, independently on the sample. On the other hand, above that pressure both the polymerization rate and the control over the reaction decreased due to the high viscosity preventing diffusion of the monomers. Moreover, taking advantage of the high pressure polymerization, we had a unique opportunity of exploring and better understanding a correlation among molecular weight, M n , the glass transition temperature, T g , and the dc conductivity, σ dc , for a very wide range of M n (up to 430 kg/mol) polymers of various backbone rigidity. We observed that the evolution of T g with M n follows a typical Fox-Flory relation. Nevertheless, T g decreases with an increase in the size of the monomer. Additionally, a similar chemical structure dependence was observed for the dc conductivity, which seems to strongly depend on the rigidity of the produced polymers. It can be seen that the higher rigidity of the polymer (longer alkyl chain of side group), the higher σ dc . We believe the results reported herein offer an easy alternative way to synthesis of well-defined polyelectrolytes of moderate/high conductivity in shorter reaction times, and expand our knowledge of their properties and the correlations among them. [ABSTRACT FROM AUTHOR]

Dissolution of bicalutamide processed with polyvinylpyrrolidone by either supercritical carbon dioxide or ball milling has been investigated. Various compositions as well as process parameters were used to obtain binary systems of the drug with the carrier. Thermal analysis and powder X-ray diffractometry confirmed amorphization of bicalutamide mechanically activated by ball milling and the decrease in crystallinity of the supercritical carbon dioxide-treated drug. Both methods led to reduction of particles size what was confirmed by scanning electron microscopy and laser diffraction measurements. Moreover, the effect of micronisation was found to depend on the parameters of applied process. Fourier transform infrared spectroscopy revealed the appearance of intermolecular interactions between drug and carrier molecules that play an important role in the stabilization of amorphous form of the active compound. Changes in crystal structure combined with reduced size of particles of bicalutamide dispersed within polymer matrix were found to improve dissolution of bicalutamide by 4 to 10-fold in comparison to untreated drug. It is of particular importance as poor dissolution profiles are considered to be the major limitation in bioavailability of the drug. [ABSTRACT FROM AUTHOR]

Three dimensional printing technology is gaining in importance because of its increasing availability and wide applications. One of the three dimensional printing techniques is Fused Deposition Modelling (FDM) which works on the basis of hot melt extrusion–well known in the pharmaceutical technology. Combination of fused deposition modelling with preparation of the orodispersible film with poorly water soluble substance such as aripiprazole seems to be extra advantageous in terms of dissolution rate. 3D printed as well as casted films were compared in terms of physicochemical and mechanical properties. Moreover, drug-free films were prepared to evaluate the impact of the extrusion process and aripiprazole presence on the film properties. X-ray diffractometry and thermal analyses confirmed transition of aripiprazole into amorphous state during film preparation using 3D printing technique. Amorphization of the aripiprazole and porous structure of printed film led to increased dissolution rate in comparison to casted films, which, however have slightly better mechanical properties due to their continuous structure. It can be concluded that fused deposition modelling is suitable technique and polyvinyl alcohol is applicable polymer for orodispersible films preparation. [ABSTRACT FROM AUTHOR]

In this paper, we have investigated dielectric response at ambient and elevated pressure of poly(mercaptopropyl)methylsiloxane (PMMS) based oligomeric brushes, where the thiol moiety was substituted by various butyl acrylate isomers (n -butyl acrylate (nBA), iso -butyl acrylate (isoBA), tert -butyl acrylate (tertBA)). It was found that the glass transition temperature, T g , of PMMS is much lower with respect to the other systems despite its ability to form weak hydrogen (H) bonds. What is more, the length scale of cooperativity was the highest in homopolymer and scaled with the steric hindrance of the graft. We also demonstrated that in the examined grafted copolymers, there is one broad relaxation process in dielectric spectra which is wider than that recorded in mechanical response. That probably means that similarly to PMMS, there are two relaxation processes above T g in grafted copolymers. However, due to similar timescale, they cannot be separated. Further, high-pressure experiments revealed that pressure coefficient of the glass transition temperature, d T g / d p , as well as the activation volume, Δ V , calculated for the segmental process surprisingly does not scale with either the size of monomer nor steric hindrance. This unexpected result must be related to the specific structure adopted by the studied grafted oligomers. Presented herein data expand our understanding on the impact of topology on the dynamics of polymers at ambient and high pressure. [Display omitted] • The glass transition temperature is strongly affected by a graft structure. • All grafted materials revealed the broad segmental relaxation process. • The shape of the α -process remains constant with pressure for all materials. • The pressure coefficient of the glass transition changes with graft structures. [ABSTRACT FROM AUTHOR]

Hyperbranched polymers are macromolecular systems of high branching density. They play a key role in the forefront of macromolecular synthesis for having features different from those of non-hyperbranched polymers and unique properties that make them amenable for use in a variety of applications. This paper presents the results from the synthesis of hyperbranched polymers of different molecular architecture, i.e., spherical and cylindrical. Also characterization of their thermal and dynamic properties is provided. Atom transfer radical polymerization from star and linear pre-former macroinitiators produced hyperbranched systems based on methyl methacrylate and lauryl methacrylate. Thermal characterizations by TGA and DSC allowed different types of interactions and degradation mechanisms as a function of the determined polymer architecture. NMR studies revealed the effect of molecular architecture on monomers tacticity along the molecular brushes. Spherical architecture yielded a higher isotactic percentage than cylindrical architecture did, thus indicating a specific stereochemistry as a function of the macro-initiator morphology. Broadband dielectric spectroscopy, one of the most powerful techniques to study the dynamics of molecular systems revealed not only different patterns of behavior of hyperbranched polymers of different architectures but also results in agreement with NMR on stereochemistry as a function of molecular architecture. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, dielectric and calorimetric studies of the small-molecule glass former allyl acetoacetate monomers as well as its newly synthetized homopolymer and copolymers with different styrene composition were performed in both the liquid and glassy states. The molecular dynamics studies by the broadband dielectric spectroscopy and the stochastic temperature modulated differential scanning calorimetry enabled us to explore relaxation processes of examined materials in the wide frequency range. We found that the copolymers reveal two co-existing glass transitions characterized by the glass transition temperatures, which are very close to those of the corresponding homopolymers. These results suggest that the copolymers exhibited some sequences of acetoacetate units with a microphase-separated morphology in agreement with the value of reactivity ratio previously determined. We investigated effects of copolymerization compositions on the glass transition temperature, the isobaric fragility index, the dielectric and calorimetric intensity, and the dynamic heterogeneity on the glass transitions of the materials. [Copyright &y& Elsevier]

In this article, the effect of mesoporous silica (MS) on the physical stability and molecular dynamics of the amorphous form of Celecoxib (CEL) is investigated. It has been proven that the recrystallization process of CEL slows down with increasing the MS content. Beside the elongation of stabilization time with the increase silica content leads to an increase in the amorphous drug fraction remaining after the finished crystallization. The conducted analyses show that the observed inhibition of CEL's recrystallization is associated with the formation of a monomolecular drug layer on the silica's surface. The performed non-isothermal dielectric studies of CEL + MS systems having both fully and partially amorphous CEL shows that the biggest impact of the drug's the temperature dependences of structural relaxation time τ α (T) has a crystalline fraction of the API. Silica, even in high concentration, does not modify the temperature dependence of structural relaxation of CEL. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Positron annihilation lifetime spectroscopy (PALS), a method well established for the study of polymers, is employed to characterize the temperature dependence of the free volume through T g in the amorphous pharmaceutical Verapamil hydrochloride. From the PALS spectra analyzed with the routine LifeTime9.0 the size (volume) distribution of local free volumes (subnanometre-size holes), its mean, , and mean dispersion, σ h, were calculated. A comparison with the macroscopic volume from PVT-experiments delivered the hole density and the hole free volume fraction and in that way a complete characterization of the free volume microstructure. These data are used in correlation with structural (α-) relaxation data from broad-band dielectric spectroscopy in terms of the Cohen–Turnbull free volume model. An extension of this model, distinctions in the free volume behaviour of the glassy and supercooled-liquid state and different ways of extrapolating the equilibrium part of the free volume into the temperature range of the glass are discussed. The potential of the PALS method for the study of pharmaceuticals is briefly reviewed and some recently developed applications (analysis of density fluctuations) are illuminated. [ABSTRACT FROM AUTHOR]

Abstract: Dielectric relaxation measurements were performed on two enantiomers, d- and l-arabinose and their equimolar mixture, and compared to dielectric data obtained for d-ribose. d-Arabinose differs from d-ribose by having the opposite configuration at C2. This study reveals that both d- and l- of arabinose exhibit α-relaxation peaks with the same shape for the same α-relaxation time τ α, and the same steepness index for the T g-scale T-dependence of τ α. However, the two isomers have slightly different glass transition temperatures T g’s, and their secondary γ-relaxation times also differ slightly from the previously observed γ-relaxation in d-ribose at the same temperature. However, when samples of both investigated monosaccharides are annealed at higher temperatures, their glass transition temperatures become nearly identical. This is an effect of the mutarotation process, which leads to the formation of pairs of the enantiomers and accordingly they should have the same physical properties. The width of the α-relaxation of d- and l-arabinose is broader than that of d-ribose, as reflected by the smaller stretch exponent in the Kohlrausch–Williams–Watts function used to fit the data of the former (β KWW =0.46±0.01) than the latter (β KWW =0.55±0.01). The width of the α-relaxation of racemic mixture of the d- and l-arabinose is slightly broader than that of the pure isomers. While the dielectric loss data of d-ribose in the glassy state at ambient and elevated pressures show an inflexion indicating the presence of the JG β-relaxation, the data of d- and l-arabinose show no such feature for identification of the supposedly universal JG β-relaxation. Nevertheless, on comparing the loss spectra of d-arabinose with that of d-ribose, the presence of the JG β-relaxation in d-arabinose has been rationalized. [Copyright &y& Elsevier]

In this paper, we report 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) supported high-pressure approach enforcing Ring-Opening Polymerization (ROP) of γ-butyrolactone (GBL), that due to unfavorable thermodynamics and low ring strain, is considered as a hardly polymerizable monomer. Application of Broadband Dielectric Spectroscopy (BDS) allowed us to find optimal thermodynamic conditions to perform well-controlled and notably fast polymerization (even within 1 h!), avoiding undesired crystallization process. It was shown that by varying pressure and temperature conditions, we could control molecular weight, dispersity of recovered macromolecules, as well as rate and efficiency of the reaction that are significantly altered with respect to the reference process carried out at ambient conditions. Experiments performed at respectively very low temperature T = 233 K and low/moderate pressure (p = 75–250 MPa) and much higher temperatures (T = 248–268 K) and compressions (p = 1000 MPa) yielded poly(γ-butyrolactone) (PGBL) of tailored absolute molecular weight in moderate range M n = 2.8–15.0 (up to 30.3) kg/mol and narrow/moderate dispersity ranging from Đ = 1.12–1.89. What is more, the implementation of MALDI-TOF, GPC and DSC analyses, clearly indicated that as i) the time of reaction gets longer, ii) the amount of catalyst increases, iii) the temperature lowers, the content of cyclic products in produced polymers grows. This phenomenon influences the rheological properties (viscosity), foil formation ability (films) and cell culture proliferation features of the recovered macromolecules. Presented results open a highly effective and repeatable route to produce PGBL via pressure-assisted ROP and indicate the possibility of tuning properties of this polymer by varying concentration of cycles or eventual block copolymerization with other biorelevant monomers to meet the expectations of the biotechnological industry. [Display omitted] • Organocatalyzed high-pressure assisted γ-butyrolactone Ring-Opening Polymerization. • Well-defined macromolecules (M n up to 30.3 kg/mol; low to moderate Đ = 1.12–1.89). • External catalytic effect of high pressure: reduced reaction time; increased yield. • Monitoring the polymerization progress in situ using BDS technique. • Analysis: NMR, GPC, MALDI, DSC, SEM, rheology, cytotoxicity, cell proliferation. [ABSTRACT FROM AUTHOR]

In this paper, the molecular dynamics as well as inter- and intramolecular interactions in the homogenous solid dispersions (SDs) of active pharmaceutical ingredient - probucol (PRO) with acetylated glucose (acGLU), acetylated sucrose (acSUC), and sucrose acetoisobutyrate (aibSUC), prepared in 5:1 molar ratio, have been investigated using broadband dielectric (BD) and Fourier transform infrared (FTIR) spectroscopy. Importantly, high pressure dielectric measurements revealed that as for neat PRO, a breakdown of the isochronal structural (α) and JG- β exact superpositioning, due to increasing separation between both processes under compression, can also be detected in its mixtures with acetylated saccharides (acSACCHs). Furthermore, the analysis of temperature dependences of JG- β -relaxation times for PRO and PRO-acSACCH SDs at selected isobaric conditions indicated the increase in the cooperativity of the secondary process (reflected in the value of the activation entropy, Δ S β) at elevated pressure in all systems. The mere addition of the small amount of excipient to neat PRO (p = 0.1 MPa) resulted in a greater value of Δ S β (it was the most noticeable in the case of aibSUC). Further FTIR studies carried out on the pressure densified glasses of PRO, and binary mixtures suggested that the observed changes in the cooperativity of the JG- β -process, as well as the failure of the exact isochronal superpositioning of α - and JG- β relaxation times, are due to varying H-bond pattern in the examined single- and two-component systems at high compression/in the presence of saccharide. [Display omitted] [ABSTRACT FROM AUTHOR]

The article describes the preparation and characterization of binary mixtures of two antiandrogens used in prostate cancer treatment, i.e. flutamide (FL) and bicalutamide (BIC), as well as their ternary mixtures with either poly(methyl methacrylate-co-ethyl acrylate) (MMA/EA) or polyvinylpyrrolidone (PVP). The samples were converted into amorphous form to improve their water solubility and dissolution rate. Broadband dielectric spectroscopy and differential scanning calorimetry revealed that FL-BIC (65%) (w/w) does not tend to crystallize from the supercooled liquid state. We made the assumption that the drug-to-drug weight ratio should be maintained as in the case of monotherapy so we decided to investigate the system containing FL and BIC in 15:1 (w/w) ratio with 30% additive of polymers as stabilizers. Our research has shown that only in the case of the FL-BIC-PVP mixture the crystallization has been completely inhibited, both in glassy and supercooled liquid state, which was confirmed by X-ray diffraction studies. In addition, we performed solubility and dissolution rate tests, which showed a significant improvement in solubility of ternary system as compared to its crystalline counterpart. Enhanced physical stability and water solubility of the amorphous ternary system makes it promising for further studies. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Over the last decade, the volume has been envisioned as a critical variable controlling the dynamics of glass-forming systems in general, and charge transport of ionic conductors in particular. Herein, we use theoretical and experimental approaches to investigate the volume effects in a specific 1,2,3-triazolium-based poly(ionic liquid) (PIL) at both the macro and nano scales. The size of the local free volume cavity in the studied system was determined by positron annihilation lifetime spectroscopy (PALS). On the other hand, the theoretical approach enabled us to estimate the hard-core volume (V hc) and thus free volume (V f) in the studied PIL. Since the experimental value determined for V f is relatively large it can be considered as the main factor controlling the superionic properties of this material. Furthermore, the analysis of specific volume and relaxation dynamics in T - P plane in terms of the locally correlated lattice (LCL) and cooperative free volume (CFV) models shows that none of them works for the studied system. Image 1 • Investigations into the size of local free volume cavity of polymerized ionic liquids by means of PALS. • Studies on the effect of free volume on ion dynamics in polymerized ionic liquids. • The failure of the LCL and CFV models in case of ion-conducting polymers. [ABSTRACT FROM AUTHOR]

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 NTf 2 -) (VBIm/NTf 2 ,VBIm/Cl, VBPy/NTf 2 ,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, T g , of the synthesized herein linear homopolymer-based systems (both VBIm/NTf 2 and VBPy/NTf 2 - -based) increases with their molecular weight, M n , 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, σ dc (σ dc ~10−15 S/cm vs. σ dc ~10−16S/cm for PVBIm/NTf 2 vs. PVBPy/NTf 2 - at T g determined from calorimetric experiments) when compared to N -conjugated one (σ dc ~10−9 S/cm for poly(N -vinyl-imidazole)/NTf 2). Interestingly, the ionic conductivity value at T g 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 σ dc , reaching values σ dc ~10−4S/cm and σ dc ~10−7S/cm, respectively. Image 1 • Solid-like and gel-like imidazolium- or pyrrolidinium-based PILs of different topology have been produced. • The solid-like systems were synthesized by AGET ATRP or RAFT, whereas the gel-like ones via thiol-ene photopolymerization. • T g of solid system increases with the M n increase as suggested by Fox-Flory relation independently on the polymerized monomer. • Grafted poly(siloxane-based) PILs were characterized by similar ionic conductivity at T g as its corresponding linear analogs. • Both imidazolium-based systems with NTf 2 - anions revealed high ionic conductivity at 293 K (σ dc ~10−4–10−7 S/cm). [ABSTRACT FROM AUTHOR]

The article describes the preparation and characterization of 3D-printed tablets with bicalutamide obtained using two-material co-extrusion-based fused deposition modeling (FDM). This method is a modification of typical two-material FDM where separate nozzles are used to print from two filaments. In this work we used a ZMorph® 3D printer with DualPro printhead which allows us to co-extrude two filaments through a single nozzle. This approach gives the opportunity to modify tablet properties in a wide range, especially the dissolution rate, by producing dosage forms with a complex design. The great advantage of this method is that switching between immediate dosage form and controlled release does not require any change in the 3D-printer set-up. We checked the accuracy of co-extrusion printing simply by weighing the amounts of soluble and insoluble material in the printed object as well as calculating the volumes of the printed objects from micro computed tomography (µ-CT) images. We printed several tablets with a different design including simple one-material tablets, two- and three-compartment tablets with various internal structure and composition of the printing path. The dissolution tests were conducted in sink and non-sink conditions. We obtained tablets with desired bicalutamide dissolution profiles, i.e. immediate, controlled, and combined. The formation of spatial matrix slows down the dissolution in controlled and combined release bicalutamide tablets what was confirmed by µ-CT analysis before and after dissolution. Image, graphical abstract [ABSTRACT FROM AUTHOR]

One of the greatest problems of pre-clinical development of new chemical entities is their poor aqueous solubility. Herein, we focus our attention on MD20 – a novel calcium channel blocker that selectively blocks T-type calcium channel (Ca v 3.2) over L-type calcium channel (Ca v 1.2). To avoid future problems with limited solubility of this compound, an amorphous form of MD20 was obtained and thoroughly investigated by various experimental techniques. The thermal properties of both crystalline and amorphous MD20 were examined by differential scanning calorimetry and thermogravimetry. Dielectric spectroscopy studies of MD20 at T < T g revealed that this compound possesses as many as four secondary relaxation processes. The molecular dynamics of the supercooled sample was investigated by dielectric and mechanical spectroscopies. In this paper, a comparison of the relaxation dynamics of supercooled MD20 obtained from both of these experimental techniques is presented. On the basis of the dielectric studies, the time of physical stability of the investigated material (at T = 298 K) was predicted as 150 years. Finally, we have performed experimental long-term stability tests, which showed that amorphous MD20 did not reveal any signs of re-crystallization for at least 260 days. Image, graphical abstract [ABSTRACT FROM AUTHOR]

The article describes the preparation and characterization of binary mixtures of two antiandrogens used in prostate cancer treatment, i.e. flutamide (FL) and bicalutamide (BIC), as well as their ternary mixtures with either poly(methyl methacrylate- co -ethyl acrylate) (MMA/EA) or polyvinylpyrrolidone (PVP). The samples were converted into amorphous form to improve their water solubility and dissolution rate. Broadband dielectric spectroscopy and differential scanning calorimetry revealed that FL-BIC (65%) (w/w) does not tend to crystallize from the supercooled liquid state. We made the assumption that the drug-to-drug weight ratio should be maintained as in the case of monotherapy so we decided to investigate the system containing FL and BIC in 15:1 (w/w) ratio with 30% additive of polymers as stabilizers. Our research has shown that only in the case of the FL-BIC-PVP mixture the crystallization has been completely inhibited, both in glassy and supercooled liquid state, which was confirmed by X-ray diffraction studies. In addition, we performed solubility and dissolution rate tests, which showed a significant improvement in solubility of ternary system as compared to its crystalline counterpart. Enhanced physical stability and water solubility of the amorphous ternary system makes it promising for further studies. Unlabelled Image [ABSTRACT FROM AUTHOR]