Hot-stage Microscopy Research Articles

THERMOANALYTICAL STUDIES ON NEW POLYMORPHIC FORMS OF PROPYL, OCTYL AND DODECYL GALLATES

• propyl , octyl and dodecyl gallates were submitted to thermal analysis • thermal analysis revealed melting followed by degradation in high temperatures • when cooled just after melting new polymorphic forms crystalized • X-ray diffraction and hot stage microscopy confirmed these polymorphic forms • a complete thermal behavior mechanism was proposed for these antioxidants The thermal behavior of propyl (PG), octyl (OG) and dodecyl (DG) gallates, three antioxidants widely used in fuel and food industries, was evaluated by thermoanalytical techniques (TG, DTA, DSC and hot stage microscopy), and complementary techniques, such as FTIR-ATR and XRD. All of them presented melting in characteristic temperatures during heating. The resulting liquid phases crystallized in different solid forms when cooled just after melting. However, when the samples were heated beyond melting temperature, they decomposed. Although thermal studies were conducted at higher temperature than those in which they are regularly used, this work provided relevant information regarding their thermal behavior at higher temperatures. Data from XRD, FTIR-ATR and hot stage microscopy were used to confirm the presence of new polymorphs. Finally, based on these results mechanisms describing the thermal behavior of PG, OG and DG were proposed.

Mechanochemical synthesis and characterization of a novel AAs–Flucytosine drug–drug cocrystal: A versatile model system for green approaches

Mechanochemistry approach is addressed herein for the green formation of a novel 1:1 drug–drug cocrystal (DDC) involving the antifungal prodrug Flucytosine (5FC) and the non-steroidal anti-inflammatory acetylsalicylic acid (AAS). This DDC was designed considering the huge market demand for new antifungal agents and the antifungal activity reported for some non–steroidal anti–inflammatory drugs, including AAS. The structure-properties characterization of the 5FC-AAS cocrystal was determined by X–ray diffraction (single crystal and powder), differential scanning calorimetry, thermogravimetric analysis, spectroscopic techniques (Raman and Fourier transform infrared), and hot–stage microscopy. The strong O–H…O and N–H…O hydrogen bonds formed between the hydroxyl group of AAS and the carbonyl and amine groups of two symmetry–related 5FC molecules maintain the crystalline packing, together with the same classical R22(8)homodimers observed in other 5FC cocrystals. The direct exposure under accelerated conditions (75% relative humidity/40 °C for 7 days) and at 12–months at room condition were also evaluated. Although the hygroscopicity addressed to 5FC was observed in the cocrystal during the stability studies, nevertheless this property discrepancy can easily be handled with the use of appropriate excipients and packing. DDC production was interestingly achieved by solvent evaporation, neat, and solvent-drop grinding (manually and in a ball-milling), resulting in a very fast production with suitable yield. In this sense, it is believed that this new model DDC will serve as a potential binary base cocrystal system for further developments of related higher dimensional cocrystals in this field, alongside other important drug molecules or in relation to the feasibility of using it therapeutically.

Quantification of Compatibility Between Polymeric Excipients and\xa0Atenolol Using Principal Component Analysis and Hierarchical\xa0Cluster Analysis

An important challenge to overcome in the solid dosage forms technology is the selection of the most biopharmaceutically efficient polymeric excipients. The excipients can be selected, among others, by compatibility studies since incompatibilities between ingredients of the drug formulations adversely affect their bioavailability, stability, efficacy, and safety. Therefore, new, fast, and reliable methods for detecting incompatibility are constantly being sought. Hence, the purpose of this work was to assess the usefulness of a heating, cooling, and reheating differential scanning calorimetry (DSC) program for detecting potential incompatibilities between atenolol, an active pharmaceutical ingredient (API), and polymeric excipients. Hot-stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy, and powder X-ray diffraction (PXRD) were used as supporting techniques. Additionally, principal component analysis (PCA) and hierarchical cluster analysis (HCA) served as tools to support the interpretation of the data acquired from the DSC curves and FTIR spectra. As the alterations in the shape of the DSC peak of atenolol which are indicative of incompatibility are visible only on the cooling and reheating curves of the mixtures, the DSC heating–cooling–reheating program was found to be very useful for identifying potential incompatibilities in the binary mixtures of atenolol and polymeric excipients. The melting and recrystallization of atenolol alone and in its mixtures were also confirmed by HSM, while FTIR displayed changes in the spectra of mixtures due to incompatibility. These studies revealed that atenolol is incompatible with hydroxyethylcellulose, hypromellose, and methylcellulose. PXRD measurements at room temperature revealed that the crystallinity of atenolol did not change in these mixtures. However, its crystallinity was reduced in the mixtures previously heated up to 155 °C and then cooled to 25 °C.Graphical abstract

Improved solubility of gefitinib achieved by the water-acetone solvate

A solvate of gefitinib (1) was synthesized and characterized by single-crystal and powder X-ray diffraction, IR spectrum, TG/DSC, as well as hot-stage microscopy. 1 crystallizes in P21/c space group, whose asymmetric unit contains one gefitinib, two water and one molecular acetone. The structural and Hirshfeld surface analysis indicate that the conformation of the gefitinib molecule changes significantly due to the inclusion of the solvent molecules, hence the gefitinib in 1 shows distinctive intermolecular interactions and molecular packing. These differences account for the highly enhanced solubility of 1 in both acidic and neutral solutions as compared with the commercial gefitinib.

Effect of a Dwell Stage in the Cure Cycle on the Interphase Formation in a Poly(ether imide)/High Tg Epoxy System

Epoxies are inherently brittle materials and to overcome this brittleness, a second microphase (i.e., thermoplastic) is typically added. This modification of epoxy resin using thermoplastics results in reaction-induced phase separating morphologies in the micrometer range. In this study, the influence of the curing history, beyond phase separation, on the interphase formation and final morphology of PEI and the high Tg epoxy system is investigated. Several cure cycles were examined, each with a first dwell temperature ranging from 120 to 180 °C for a given time up to the onset of phase separation (OPS) or up to the 80% degree of cure (80% DOC) and then with a second dwell at 200 °C for 20 min to complete the cure cycle. Hot-stage microscopy experiments were carried out at several first dwell temperatures before final conversion at the second dwell. The morphologies and resulting droplet size distribution at the interphase, after the final cure, were analyzed through scanning electron microscopy. Results showed that the diffusion distance was significantly higher in the case of OPS as compared to the 80% DOC case, particularly at lower first dwell temperatures. This behavior was attributed to the fact that, in the case of OPS, polymeric chains were still in a mobile state and diffused further during the second dwell curing stage, while at 80% DOC, polymeric chains were completely bound but still diffuse due to non-stoichiometric curing. This restricted mobility of polymeric chains after phase separation (80% DOC) resulted in a larger number of smaller droplets as compared to the OPS case.

Effect of the coexistence of CO2 and H2 on the kinetics of cerium hydriding

The reactions of cerium in hydrogen mixed with different concentrations of CO2 were conducted by using a pressure-volume-temperature (PVT) method combined with an in situ hot-stage microscope. CO2 has a great suppression effect on the hydriding reaction of cerium. The existence of CO2 leads to longer induction time, less pitting, and much slower hydriding rate. It is found that the induction time of hydriding reaction grows exponentially as a function of CO2 concentrations. Besides, the nucleation and growth of hydride spots are also suppressed with increase of CO2 concentrations. Scanning electron microscopy (SEM) and in situ optical microscope measurements reveal that the hydride spots formed in H2-CO2 mixture have a prolate hemispherical morphology while the normal hydride spots formed in pure H2 show an oblate hemispherical morphology. Thermal desorption results indicate CO2 preferentially adsorbs on the active sites of CeO2 surface resulting in block of hydrogen dissociation, which is accountable for the observed hydriding inhibition phenomenon. Our studies provide new insights into the CO2 effect on the hydriding process of active metals.

Corrosion of magnesia-chromite refractory by PbO-rich copper slags

The work presents corrosion of direct-bonded MgOCr refractory by three types of PbO-rich copper slags. Pellet test, contact corrosion test and hot stage microscopy test enabled to study corrosion phenomena at 1300 °C and 1450 °C, respectively. The structure and microstructure of the after-corrosion samples were deeply analyzed, with the former one aided by development of image detection algorithms. Slags infiltrated the refractory through open pores and cracks. Slag components diffused into refractory and changed its original composition. Forsterite solid solution, Mg2SiO4 s.s., which formed as the only corrosion product caused swelling of microstructure and disintegration of magnesia-chromite direct bonds, critical for the performance of refractory.

Miscibility and Solubility of Caffeine and Theophylline in Hydroxypropyl Methylcellulose.

As amorphization may improve the solubility and bioavailability of a drug substance, the aim of this work was to assess to what extent the crystallinity of caffeine (CAF) and theophylline (TF) can be reduced by homogenization with a polymeric excipient. To realize this purpose, the physical mixtures of both methylxanthines with hydroxypropyl methylcellulose (HPMC) were examined using differential scanning calorimetry (DSC), hot-stage microscopy (HSM), Fourier-transform infrared (FTIR) and Raman spectroscopy. Moreover, phase diagrams for the physical mixtures were calculated using theoretical data. Results of DSC experiments suggested that both CAF and TF underwent amorphization, which indicated proportional loss of crystallinity for methylxanthines in the mixtures with HPMC. Additionally, HSM revealed that no other crystalline or amorphous phases were created other than those observed for CAF and TF. FTIR and Raman spectra displayed all the bands characteristic for methylxanthines in mixtures with HPMC, thereby excluding changes in their chemical structures. However, changes to the intensity of the bands created by hydrogen bonds imply the formation of hydrogen bonding in the carbonyl group of methylxanthines and the methyl polymer group. This is consistent with data obtained using principal component analysis. The findings of these studies revealed the quantities of methylxanthines which may be dissolved in the polymer at a given temperature and the composition at which methylxanthines and polymer are sufficiently miscible to form a solid solution.

Thermally induced polymorphic transformation of Hexanitrohexaazaisowurtzitane (CL-20)

To investigate the polymorphic transformation and crystal morphology changes of ε-CL-20 under different thermal stimuli, isothermal and non-isothermal experiments were conducted using a hot stage microscope and in-situ X-ray powder diffraction. It was found that the ε- and γ- phases coexisted at 120 °C (9.727 wt% γ-CL-20), and the ε→γ phase transformation occurred between 115 and 120 °C and reached completion at 130 °C. The ε-CL-20 expanded isotropically in the temperature range of 25 to 115 °C. About a quarter of the ε-CL-20 transformed after being heated at 120 °C for 12 h, whereas almost all of ε-CL-20 transformed after being heated at 150 °C for 12 h. Under the microscope, the expansion of crystal volume, changes of crystal morphology, and phenomena of decomposition were observed during heating. Molecular dynamics simulation and Rietveld refinement were conducted to verify the experimental results. A solid-solid phase transition mechanism is presented.

Preparation of some polyamides of diaminodibenzo-18-crown-6 and Studying their liquid crystalline properties

Crown ethers are very important compounds in the extraction of alkali, alkaline earth, and transition metal ions that by formation of complexes with these ions .Crown ether polymers may have more ability of extraction compared with their monomers .In addition these polymers may be less poisonous, inexpensive, and can be used as catalysts.
 This study had been aimed for preparation of four models, and seven polyamides of dibenzo-18-crown-6.
 First step in this preparation was the nitration of dibenzo-18-crown-6,followed by reduction of the nitro group .Then the polymerization was carried out in an atmosphere of nitrogen gas .The prepared compounds have been characterized using ( IR ) spectra ,and ( CHN ) mass spectra. The cis and trans diaminodibenzo-18-crown-6 have been analyzed using the proton magnetic resonance spectra ( 1HNMR ) .these results have been in agreement with the expected structure of these products. The inherent viscosity of these polymers was measured, and was found to have intermediate molecular weight .The liquid crystalline properties of these polymers was also studied using Differential Scanning Calorimeter ( DSC ), and hot-stage microscope .The polymers of the trans isomer give a semectic, while those of the cis one did not give any liquid crystalline properties.

Thermal Behavior of the Porous Polymer Composites Based on LDPE and Natural Fillers Studied by Real Time Thermal Microscopy

Foaming of the biodegradable polymer composites and melting of the gas-filled materials were studied using thermal microscopy. Composite materials under investigation were based on the low density polyethylene and natural products used as the polymer composite fillers: wood flour and corn starch. Porous structure of the composite material was obtained using a chemical porogen “Hydrocerol BIF”. It has been shown that the foaming and melting processes occur differently in the polymer composite samples containing either different amount of the fillers or the same content of the filler with different particle size fractions. Thermal behavior of the composite samples was shown to be different from the behavior of pure polyethylene, which indicates non-additivity (superadditivity) of the contribution of the above components to the thermal behavior of the final composite material. All the results obtained using heating stage (hot stage) microscopy were in good agreement with the SEM and DSC data.

Exploring Taxifolin Polymorphs: Insights on Hydrate and Anhydrous Forms.

Taxifolin, also known as dihydroquercetin, possesses several interesting biological properties. The purpose of the study was to identify polymorphs of taxifolin prepared using crystallization in different solvents. Data from X-ray powder diffraction, differential scanning calorimetry, and thermogravimetry enabled us to detect six different crystalline phases for taxifolin. Besides the already known fully hydrated phase, one partially hydrated phase, one monohydrated phase, two anhydrous polymorphs, and one probably solvated phase were obtained. The unit cell parameters were defined for three of them, while one anhydrous polymorph was fully structurally characterized by X-ray powder diffraction data. Scanning electron microscopy and hot stage microscopy were also employed to characterize the crystallized taxifolin powders. The hydrate and anhydrous forms showed remarkable stability in drastic storage conditions, and their solubility was deeply evaluated. The anhydrous form converted into the hydrate form during the equilibrium solubility study and taxifolin equilibrium solubility was about 1.2 mg/mL. The hydrate taxifolin intrinsic dissolution rate was 56.4 μg cm−2 min−1. Using Wood’s apparatus, it was not possible to determine the intrinsic dissolution rate of anhydrous taxifolin that is expected to solubilize more rapidly than the hydrate form. In view of its high stability, its use can be hypothesized.

Salts and Polymorph Screens for Bedaquiline

Bedaquiline is used to treat multi-resistant tuberculosis in adults. The fumarate salt is commercially available and used in the product Sirturo. To provide open access to bedaquiline molecule once the patent on the chemical substance expires, new salts were screened. This work offers additional information on the bedaquiline system, as new salts may present better pharmacokinetic properties. The current studies focus on the attempted isolation of the acetate, benzoate, benzenesulfonate, hydrobromide, succinate, hydrochloride, tartrate, lactate, maleate, malate, and mesylate salts of bedaquiline. Potential salts were screened using a unique combination of conventional screening, and small-scale experiments supplemented by crystallographic analysis and infrared microspectroscopy. Salts were prepared on a larger scale by dissolving 1:1 ratios of the individual salt formers and bedaquiline base (30 mg, 0.055 mmol) in different solvents and allowing the solutions to evaporate or crystallize. X-ray diffraction (XRD) techniques and spectroscopic and thermal analyses were employed to characterize the salts. The benzoate and maleate salts were selected as lead candidates after reviewing preliminary characterization data. To determine the most stable forms for the leads, a polymorph screen was conducted using solvents of various polarities. These salt screens successfully generated five new salts of bedaquiline, namely, benzoate, maleate, hydrochloride, besylate, and mesylate. The existence of these salts was confirmed by powder XRD, proton NMR, and IR spectroscopies. TGA and DSC thermal analysis along with hot-stage optical microscopy were further used to characterize the salts. The polymorph screen conducted on the salts suggested the absence of additional polymorphs at 1 g scale.

Quantum crystallography, spectroscopic methods and hot-stage microscopy in the study of chromic multicomponent materials

Quantum crystallography, spectroscopic methods and hot-stage microscopy in the study of chromic multicomponent materials

Effect of BaO substitution for CaO on the structural and thermal properties of SiO2–B2O3–Al2O3–CaO–Na2O–P2O5 bioactive glass system used for implant coating applications

The present study replaced 3.30 and 9.00 mol.% BaO for CaO in a SiO2–B2O3–Al2O3–CaO–Na2O–P2O5 bioactive glass system used for implant coating applications. Variations of the glass structure, thermal properties, cytotoxicity, and radiopacity of glasses were studied. As demonstrated by the results, upon adding barium oxide to the glass structure, the weight density increased significantly, while a slight decrease in oxygen density was determined. Introducing barium oxide into glass composition did not cause any considerable change in the spectra of FTIR and Raman. It was demonstrated that the amount of bridging oxygen in the glass structure remained quite unaffected. The hot stage microscopy evaluations revealed further shrinkage of barium-containing frits due to lower viscosity and hence, higher viscous flow of these glasses. By substituting barium oxide for calcium oxide and increasing its concentration, the glass transition temperature (Tg) and the dilatometric softening temperature (Td) decreased, while the thermal expansion coefficient increased. Moreover, upon substituting 9 mol.% barium oxide for calcium oxide, a 30 °C reduction in maximum sintering temperature (Tms) of the glass was obtained, whereas the shrinkage rate was increased 1.7 times. It was indicated that the sintering process of barium-incorporated glasses would easily proceed without any phase crystallization. The barium-incorporated glasses exhibited more radiopacity. Additionally, no cytotoxic effect was caused by the substitution, and the Ba-containing glasses could be used for biomedical applications and implant coating as well.

Evaluation of ashes from agro-industrial biomass as a component for producing construction materials

Reducing the energy consumption in ceramic kilns because of lower firing temperatures is very relevant in terms of both fuel cost and carbon dioxide (CO2) emissions. In this sense, this work evaluates changes in the sintering starting temperature when ashes from the combustion of agro-industrial wastes (exhausted olive cake and almond shell) are added (0–20 wt%) to two types of clays showing different plasticity and refractory behaviour. Both, reductions and increases in this temperature were measured by means of a Hot Stage Microscopy (HSM) which registers changes in the height of the sample subjected to a specific temperature profile. A selection of the more adequate clay-ash mixtures attending to their sintering behaviour were performed. Fired pieces of the selected mixtures were subjected to further characterization (tensile strength, linear shrinkage, firing loss, bulk density, porosity and water absorption) to evaluate mechanical performance when compared to the original clay. The results indicate that the sintering temperature of the clay-ash mixture is a compromise between the fluxing oxides content and the pores created by the loss of volatile matter and carbonates in the ash. While the former favours sintering, the latter inhibits it because of the appearance of gaps between mineral particles. Ash contents higher than 10% did not provide benefits in terms of melting behaviour in any case. Reductions in the sintering starting temperature up to 120 °C were reported when ash from exhausted olive cake was used, which could lead to estimated fuel-energy savings around 2 €/t of product (with around 6 kg/t of CO2 emissions avoided). Moreover, percentages above 5% as well as the use of ashes from almond shells could be an attractive way for producing materials with enhanced insulation properties.

PREPARATION, CHARACTERIZATION AND DISSOLUTION OF SOLVENT EVAPORATED SIMVASTATIN SOLID DISPERSIONS

Simvastatin an antihyperlipidemic BCS class II drug, suffering from poor water solubility. This problem may affect the bioavailability as well as pharmacological action of the drug. To overcome this solubility issue, solid dispersions of simvastatin were prepared and compared with marketed formulation “SIMVOTIN 20” in this study. Solid dispersions of simvastatin were prepared by using the solvent evaporation method. Solid dispersions of simvastatin with PVP K90 (1:1-1:5), HPMC E50 (1:1-1:5), and Poloxamer 450 (1:1 to 1:3) with and without 1% Sodium lauryl sulfate were prepared by a solvent evaporation method. The characterization studies such as Fourier transform infra-red (FTIR), differential scanning calorimetry (DSC), Hot stage microscopy (HSM), powdered X-ray crystallographic studies (PXRD) were performed to evaluate physiochemical change in the optimized formulation. The dissolution test showed the enhancement of dissolution as compared to the pure drug, physical mixture and marketed formulation “SIMVOTIN 20” in all three types of formulation, but formulation containing ratio 1:3:1 (simvastatin: Poloxamer: 1% SLS) showed the faster drug release as compared to other formulations. The Fourier transform infra-red (FTIR) study showed no interaction between the drug and polymers. The differential scanning colorimetry (DSC) and hot stage Microscopy (HSM) showed change in nature of the drug further verified by powdered X-ray crystallographic studies (PXRD) study. These studies showed the amorphous nature of the formulation may be a reason for enhancement of dissolution rate. Hence solid dispersion formulation may be an effective approach for solubility enhancement of a BCS Class II drug.

The kinetics of thermal decomposition and hot-stage microscopy of selected energetic cocrystals

The thermal decomposition of four energetic cocrystals composed of 4-amino-3,5-dinitropyrazole (ADNP)/diaminofurazan (DAF), 2,4,6-trinitrotoluene (TNT)/ 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL20), 1,3,5,7-tetranitro-1,3,5,7-tetrazacyclooctane (HMX)/CL20, and 1-methyl-3,5-dinitro-1,2,4-triazole (MDNT)/CL20 were studied using simultaneous differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), and hot-stage microscopy. The kinetic parameters of their thermal decomposition reaction were determined using the Kissinger and Ozawa kinetic analysis methods. Each cocrystal’s peak exothermic temperature (decomposition temperature), activation energy, and pre-exponential constant are reported. Furthermore, these parameters from each cocrystal were compared to the same parameters from the corresponding stoichiometric physical mixture in order to identify changes in behavior attributable to the cocrystallization process. For ADNP/DAF, the cocrystal shows an 8% increase in the peak exotherm temperature and a 11-13% decrease in peak activation energy as compared to its physical mixture. For TNT/CL20, this comparison shows a much smaller change in the peak exotherm temperature (

Various Molecular Arrangements Leading to Different Desolvation Rates: Research on the Stability of 2,7‐Dibromo‐9H‐carbazole Solvates

AbstractThe stability of solvates is very important in the field of crystal engineering. Molecular interaction and packing mode are important factors affecting the stability of solvates. In this study, 2,7‐dibromo‐9H‐carbazole is selected as the model compound to investigate the influence of molecular stacking mode on the stability of solvates. An anhydrous form and five solvates of 2,7‐dibromo‐9H‐carbazole are obtained by recrystallization. The desolvation phenomena of the five solvates are studied by thermogravimetric analysis, hot stage microscope, and infrared spectroscopy and it is found that the stability of the solvates is N,N‐dimethylacetamide solvate > dimethyl sulfoxide solvate > N,N‐dimethylformamide solvate > dioxane solvate > acetonitrile solvate. Crystal structures are analyzed by single crystal X‐ray diffraction and Hirshfeld surface analysis is also applied to analyze the intermolecular interactions in the crystals. The results show that the stability of the five solvates is related to the packing modes of the molecules in the crystal. It is suggested that the solute molecules and solvent molecules in the unstable solvates are arranged in the interlayer mode, while they are arranged in a staggered mode in stable solvates.

In-situ study of effect of migrating alkali metals on gasification reactivity of coal char

The migrating and diffusion of alkali metals affect catalytic gasification of coal char. The paper investigated in-situ gasification behaviors of coal char by TG and hot stage microscope, and studied catalytic performance of single NaAlO2 particle and Na distribution by SEM-EDX. The results show that in the beginning stage, the curve of carbon conversion obtained by area method is consistent with that by TG method. In the ending stage, the ash in coal char acts as framework of the particles, as a result, area of the particles keeps unchanged. Meanwhile, the ash hinders diffusion of gasifying agent into coal char, and decreases the gasification rate, so carbon conversion rate calculated by area change is lower than that from TG. The single NaAlO2 particle has catalytic performance. The coal char particles, which are closer to NaAlO2, have higher gasification reactivity, because the amount of migrating alkali is higher. The migrating distance of NaAlO2 is higher than 840 μm at 900°C.