47 research outputs found

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

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    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. As the physical instability of etoricoxib requires working out an efficient method for improving the drug’s resistance to recrystallization to maintain its amorphous form utility in potential pharmaceutical applications, we focused on finding a solution to this problem, and successfully achieved this purpose by preparing binary mixtures of etoricoxib with octaacetylmaltose. Our detailed thermal, refractometry, and molecular dynamics studies of the binary compositions near the glass transition revealed a peculiar behavior of the glass transition temperatures when changing the acetylated disaccharide concentration in the mixtures. Consequently, the anti-plasticization effect on the enhancement of physical stability could be excluded, and a key role for specific interactions in the improved resistance to recrystallization was expected. Invoking our previous results obtained for etoricoxib, the chemically similar drug celecoxib, and octaacetylmaltose, we formulated a hypothesis about the molecular mechanisms that may cause an impediment to crystal nuclei formation in the amorphous mixtures of etoricoxib with octaacetylmaltose. The most plausible scenario may rely on the formation of hydrogen-bonded heterodimers of the drug and excipient molecules, and the related drop in the population of the etoricoxib homodimers, which disables the nucleation. Nevertheless, this hypothesis requires further investigation. Additionally, we tested some widely discussed correlations between molecular mobility and crystallization properties, which turned out to be only partially satisfied for the examined mixtures. Our findings constitute not only a warning against manufacturing the amorphous form of pure etoricoxib, but also evidence for a promising outcome for the pharmaceutical application of the amorphous compositions with octaacetylmaltose

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

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    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. The chain length has a decisive impact on properties, exerting a plasticizing effect on the dynamics. Its elongation decreases glass transition temperature with slight impact on fragility. The increase in the medium-range order was manifested as a broadening of the dielectric loss peak reflected in the lower value of stretching parameter βKWW. A disagreement with the behavior observed for non-associating liquids was found as a deviation from the anti-correlation between the value of βKWW and the relaxation strength of the α-process. Besides, to explain the broadening of loss peak in PTZ with the longest (decyl) chain a slow Debye process was postulated. In contrast, the sample with the shortest alkyl chain and a less complex structure with predominant supramolecular assembly through π–π stacking exhibits no clear Debye-mode fingerprints. The possible reasons are also discussed

    Complex reorientation dynamics of sizable glass-formers with polar rotors revealed by dielectric spectroscopy

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    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 (τ0 > 10−12 s) in the Vogel− Fulcher−Tammann equation were found. The rich and highly diverse relaxation pattern was governed by the location of a dipole, its ability to rotate freely, and the degree of coupling to the motion of the entire sizable system

    Emergence of a substrate-temperature-dependent dielectric process in a prototypical vapor deposited hole-transport glass

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    Since the discovery of ultrastability, vapor deposition has emerged as a relevant tool to further understand the nature of glasses. By this route, the density and average orientation of glasses can be tuned by selecting the proper deposition conditions. Dielectric spectroscopy, on the other hand, is a basic technique to study the properties of glasses at a molecular level, probing the dynamics of dipoles or charge carriers. Here, and forthe first time, we explore the dielectric behavior of vapor deposited N, N-Diphenyl N, V -biphenyl-4,4'-diamines (TPD), a prototypical hole-transport material, prepared at different deposition temperatures. We report the emergence of a new relaxation process which is not present in the ordinary glass. We associate this process to the Maxwell-Wagner polarization observed in heterogeneous systems, and induced by the enhanced mobility of charge carriers in the more ordered vapor deposited glasses. Furthermore, the associated activation energy establishes a clear distinction between two families of glasses, depending on the selected substrate-temperature range. This finding positions dielectric spectroscopy as a unique tool to investigate the structural and electronic properties Of charge transport materials and remarks the importance of controlling the deposition conditions, historically forgotten in the preparation of optoelectronic devices

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

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    Chitosan biocoatings were successfully deposited on the Ti15Mo alloy surface via cataphoretic deposition from a solution of 1 g dm−3 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. X-ray analysis revealed the amorphous structure of the chitosan coatings on the Ti15Mo alloy surface. The conducted studies also include assessing the abrasion resistance and adhesion to the substrate of the obtained chitosan coatings. The results show that utilizing the citric acid as a solvent results in the formation of pore free coatings. The yield of the electrophoretic deposition process was in the range of 2–10 mg of deposited chitosan per 1 cm2. The obtained coatings through the unique properties of chitosan are a promising biomaterial for application in medicine

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

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    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. In contrast to G-CSF, CoPP does not increase the number of circulating T cells. Transplantation of CoPP-mobilized peripheral blood mononuclear cells (PBMC) results in higher chimerism and faster hematopoietic reconstitution than transplantation of PBMC mobilized by G-CSF. Although CoPP is used to activate Nrf2/HO-1 axis, the observed effects are Nrf2/HO- 1 independent. Concluding, CoPP increases expression of mobilization- related cytokines and has superior mobilizing efficiency compared with recombinant G-CSF. This observation could lead to the development of new strategies for the treatment of neutropenia and HSPC transplantation

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

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    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. Here, we use dielectric spectroscopy at ambient and elevated pressures to study the characteristics of the secondary relaxation in ultrastable etoricoxib, reporting a 71% decrease in dielectric strength and one decade increase in relaxation time compared to the ordinary glass. Interestingly, we find an unprecedented connection between secondary and structural relaxations in ultrastable etoricoxib in exactly the same manner as in the ordinary glass, manifested through different properties, such as aging and devitrification. These results further support and extend the general validity of the connection between the secondary and structural relaxation
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