Engineering of Rotational Dynamics via Polymorph Manipulation.

We used dielectric spectroscopy to uncover the rotational dynamics of the fluorophenyl rotor in different polymorphs of two amphidynamic crystals with identical sizable cores. The rotor solid-state dynamics were investigated in various crystalline environments. We did not change the chemical structure of the crystal itself, but while maintaining the same atomic composition, we changed the arrangement of atoms in space by taking advantage of crystal polymorphism, providing an alternative approach to one based on searching for new, chemically different entities with desirable functionality.

Dual Nature of Large and Anisotropic Glass-Forming Molecules in Terms of Debye-Stokes-Einstein Relation Revealed.

The fundamental Debye-Stokes-Einstein (DSE) relation between rotational relaxation times and shear viscosity attracts longstanding research interest as one of the most important characteristics of many glass-forming liquids. Here, we provide strong evidence, missing so far, for the relevance of anisotropy for DSE-related behavior. Dielectric spectroscopy and shear viscosity measurements were employed to get insight into the decoupling between reorientation relaxation times and viscosity for anisotropic glass-formers with dipole moments oriented parallel or perpendicular to the long molecular axis.

Image of the solid-state rotary motion encoded in the dielectric response.

The future development of advanced molecular systems with controlled rotation requires the development of an effective methodology for assessing the rotational performance of artificial machine components. We identified two patterns of the dielectric behavior for polar rotators in a static non-polar framework of sizable crystal showing relations between the spectral and molecular-level features of solid-state rotary motion. Various functionalization of phenylene rotors with a fluorine atom(s) changed rotational performance from high to low with rotational barriers ranging from 6.

Insight into properties of sizable glass former from volumetric measurements.

Sizable glass formers feature numerous unique properties and potential applications, but many questions regarding their glass transition dynamics have not been resolved yet. Here, we have analyzed structural relaxation times measured as a function of temperature and pressure in combination with the equation of state obtained from pressure-volume-temperature measurements. Despite evidence from previous dielectric studies indicating a remarkable sensitivity of supercooled dynamics to compression, and contrary to intuition, our results demonstrated the proof for the almost equivalent importance of thermal energy and free volume fluctuations in controlling reorientation dynamics of sizable molecules.

Internal Secondary Relaxation as a Dielectric Probe of Molecular Surroundings.

We investigated the secondary relaxation behavior in rotor molecules in a glassy and crystalline state by using the dielectric method. Without changing the molecular source of secondary relaxation, only by modifying the environment around the rotating unit we observed notable variations in spectral parameters. Our results show that internal rotation, like a probe, can sample the immediate surroundings with high sensitivity to molecular-level changes that impact the rotation parameters.

The influence of molecular shape on reorientation dynamics of sizable glass-forming isomers at ambient and elevated pressure.

We used dielectric spectroscopy to access the molecular dynamics of three isomers with a structure based on a sizable, partially rigid, and non-polar core connected to a polar phenylene unit differing in the position of the polar group, and, consequently, the direction and magnitude of the dipole moment to address the question how unique molecular properties, in particular large size and elongated shape, affect the dynamics. The position of the polar group differentiates the molecular shape and isomer's anisotropy and leads to different thermal and dynamic properties of the isomers. The shape of permittivity loss spectra was governed by magnitudes of the longitudinal and transverse components of dipole moment to a large extent.

Study of Thermal Properties, Molecular Dynamics, and Physical Stability of Etoricoxib Mixtures with Octaacetylmaltose near the Glass Transition.

In this paper, we thoroughly investigated the physical stability of the anti-inflammatory drug etoricoxib, which has been reported earlier to be resistant to recrystallization in its glassy and supercooled states at ambient pressure. Our unique application of the standard refractometry technique showed that the supercooled liquid of the drug was able to recrystallize during isothermal experiments in atmospheric conditions. This enabled us to determine the crystallization onset timescale and nucleation energy barrier of etoricoxib for the first time.

Insight from high-pressure dielectric studies into molecular dynamics of the itraconazole-glycerol mixture in smectic and isotropic phases.

We present here the results of high-pressure broadband dielectric spectroscopy (BDS) measurements for a mixture of liquid-crystalline drug itraconazole (ITZ) and glycerol (GLY) at a critical concentration of 5% w/w in which the nematic order is eliminated. In the investigated system, smectic-A to isotropic phase transition leaves a clear fingerprint on the dielectric response, allowing for a phase diagram creation using BDS data. By following the α-relaxation dynamics under different thermodynamic conditions, we provide insights into the effect of pressure on temperature and the phenomenology of smectic-A to the isotropic phase transition.

Complex Reorientation Dynamics of Sizable Glass-Formers with Polar Rotors Revealed by Dielectric Spectroscopy.

We present the results of dielectric measurements for three sizable glass-formers with identical nonpolar cores linked to various dipole-labeled rotors that shed new light on the picture of reorientation of anisotropic systems with significant moment of inertia revealed by broadband dielectric spectroscopy. The dynamics of sizable glass-formers formed by partially rigid molecular cores linked to small polar rotors in many respects differs from that of typical glass-formers. For instance, the extraordinarily large prefactors (τ > 10 s) in the Vogel-Fulcher-Tammann equation were found.

Broadband-dielectric-spectroscopy study of molecular dynamics in a mixture of itraconazole and glycerol in glassy, smectic-A, and isotropic phases.

Itraconazole (ITZ) is a thermotropic liquid crystal that exhibits isotropic, nematic, and smectic phases on cooling towards the glass transition upon melting. Over the years, new aspects regarding the liquid-crystalline ordering of this antifungal drug were systematically revealed. It has been shown recently that the temperature range of individual mesophases in ITZ can be modified by adding a small amount of glycerol (GLY).

The dielectric response of phenothiazine-based glass-formers with different molecular complexity.

We examined a series of structurally related glass-forming liquids in which a phenothiazine-based tricyclic core (PTZ) was modified by attaching n-alkyl chains of different lengths (n = 4, 8, 10). We systematically disentangled the impact of chemical structure modification on the intermolecular organization and molecular dynamics probed by broadband dielectric spectroscopy (BDS). X-ray diffraction (XRD) patterns evidenced that all PTZ-derivatives are not 'ordinary' liquids and form nanoscale clusters.

How can we improve the physical stability of co-amorphous system containing flutamide and bicalutamide? The case of ternary amorphous solid dispersions.

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).

Broadband Dielectric Study of Sizable Molecular Glass Formers: Relationship Between Local Structure and Dynamics.

In this Letter we report significant differences in the dielectric behavior of four nonpolymeric and sizable glass-forming molecules with related chemical structures. They belong to the recently constituted class of sizable glass-formers [Jedrzejowska et al. 2020, 101, 010603], for which the pattern of change in dielectric properties with structure has not yet been fully discovered.

Photodynamic performance of amphiphilic chlorin e6 derivatives with appropriate properties: A comparison between different-type liposomes as delivery systems.

Background: Many aspects are currently being investigated, with the aim of improving the application of PDT in the clinic by rendering it more effective. One of the current trends focuses on the use of nanocarriers. The aim of this study is to describe novel photosensitizers among polyol amide chlorin e6 derivatives for photodynamic therapy (PDT) using liposomes.

Electrophoretic deposition of chitosan coatings on the Ti15Mo biomedical alloy from a citric acid solution.

Chitosan biocoatings were successfully deposited on the Ti15Mo alloy surface cataphoretic deposition from a solution of 1 g dm of chitosan in 4% (aq) citric acid. The influence of the cataphoretic deposition parameters on quality and morphology of the obtained coatings were investigated using fluorescence and scanning electron microscopy. The functional groups' presence in chitosan chine were confirmed by ATR-FTIR methods.

Cobalt protoporphyrin IX increases endogenous G-CSF and mobilizes HSC and granulocytes to the blood.

Granulocyte colony-stimulating factor (G-CSF) is used in clinical practice to mobilize cells from the bone marrow to the blood; however, it is not always effective. We show that cobalt protoporphyrin IX (CoPP) increases plasma concentrations of G-CSF, IL-6, and MCP-1 in mice, triggering the mobilization of granulocytes and hematopoietic stem and progenitor cells (HSPC). Compared with recombinant G-CSF, CoPP mobilizes higher number of HSPC and mature granulocytes.

How can we improve the physical stability of co-amorphous system containing flutamide and bicalutamide? The case of ternary amorphous solid dispersions.

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).

Unusual dielectric response of 4-methyl-1,3-dioxolane derivatives.

In this paper, we applied broadband dielectric spectroscopy (BDS) to investigate the molecular dynamics of three 4-methyl-1,3-dioxolane derivatives (MD) whose chemical structures differ in the length of non-polar alkyl side chains. We notice that small changes within their chemical structures have a pronounced impact on parameters characterizing the supercooled dynamics of the compounds selected for this study. Our detailed analysis of the dielectric response reveals that in the supercooled-liquid state besides the structural α-relaxation a sub-α Debye-like relaxation can be clearly distinguished.

Changes in Physical Stability of Supercooled Etoricoxib after Compression.

In the case of formulations with amorphous active pharmaceutical ingredients the risk of pressure-induced recrystallization should be carefully considered. We reported here that supercooled etoricoxib (ETB), which was found as a relatively stable system with low crystallization tendency at atmospheric pressure, crystallized quickly after compression. The observed strong pressure-dependence of the induction period suggests that during compression the first step of crystallization that is nucleation may be accelerated.

Distinguishing different classes of secondary relaxations from vapour deposited ultrastable glasses.

Secondary relaxations persistent in the glassy state after structural arrest are especially relevant for the properties of the glass. A major thrust in research in dynamics of glass-forming liquids is to identify what secondary relaxations exhibit a connection to the structural relaxation and are hence more relevant. Via the Coupling Model, secondary relaxations having such connection have been identified by properties similar to the primitive relaxation of the Coupling Model and are called the Johari-Goldstein (JG) β-relaxations.

Effect of Polymer Chain Length on the Physical Stability of Amorphous Drug-Polymer Blends at Ambient Pressure.

Rational selection of polymers for amorphous drug stabilization is necessary for further successful development of solid dispersion technology. In this paper, we investigate the effect of polymer chain length on the inhibition of amorphous drug recrystallization. To consider this problem, we prepared a drug-polymer blend (in 10:1 drug to polymer ratio) containing bicalutamide (BIC) and polyvinylpyrrolidone (PVP) with different chain lengths K10, K30, and K90.

Co-Stabilization of Amorphous Pharmaceuticals-The Case of Nifedipine and Nimodipine.

Currently, a research hotspot in amorphous active pharmaceutical ingredients (APIs) is to understand the key factors that dominate recrystallization and to develop effective methods for stabilizing amorphous forms. Consequently, we investigated the influence of the global molecular mobility and structural properties on the crystallization tendency of three 1,4-dihydropyridine derivatives (nifedipine, nisoldipine, and nimodipine) in their supercooled states using differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS) techniques. The BDS is also employed to monitor the isothermal crystallization kinetics of supercooled nifedipine and nimodipine at T = 333 K under ambient pressure.

Can Storage Time Improve the Physical Stability of Amorphous Pharmaceuticals with Tautomerization Ability Exposed to Compression? The Case of a Chloramphenicol Drug.

In this article we thoroughly investigated the physical stability of the amorphous form of a chloramphenicol drug. The tendency toward recrystallization of this drug has been examined (i) at nonisothermal conditions by means of a DSC technique; (ii) at isothermal conditions and temperature close to T by means of dielectric spectroscopy; (iii) at isothermal conditions and elevated temperatures of T = 323 K and 338 K by dielectric spectroscopy; and (iv) at conditions imitating the manufacturing procedure (i.e.

Secondary relaxation in ultrastable etoricoxib: evidence of correlation with structural relaxation.

Secondary relaxations are fundamental for their impact in the properties of glasses and for their inseparable connection to the structural relaxation. Understanding their density dependence and aging behavior is key to fully address the nature of glasses. Ultrastable glasses establish a new benchmark to study the characteristics of secondary relaxations, since their enthalpy and density levels are unattainable by other routes.