Glass Transition Temperature Measurements Research Articles

Commentary: Considerations in the Measurement of Glass Transition Temperatures of Pharmaceutical Amorphous Solids

An increased interest in using amorphous solid forms in pharmaceutical applications to increase solubility, dissolution, and bioavailability has generated a need for better characterization of key properties, such as the glass transition (Tg) temperature. Although many laboratories measure and report this value, the details around these measurements are often vague or misunderstood. In this article, we attempt to highlight and compare various aspects of the two most common methods used to measure pharmaceutical Tg values, conventional and modulated differential scanning calorimetry (DSC). Issues that directly impact the Tg, such as instrumental parameters, sample preparation methods, data analysis, and “wet” vs. “dry” measurements, are discussed.

Impact of Hot-Melt Extrusion Processing Conditions on Physicochemical Properties of Amorphous Solid Dispersions Containing Thermally Labile Acrylic Copolymer

For successful formulation of amorphous solid dispersions (ASDs) using hot-melt extrusion, it is imperative to understand the effect that heat and shear rate has on the physicochemical properties of the excipient. In this study, we investigated the influence of hot-melt extrusion parameters on solvent-free binary ASDs of ibuprofen (IBU), a model active pharmaceutical ingredient, in methacrylic acid-ethyl acrylate copolymer type A, 1:1, EUDRAGIT® L100-55 (EUD). To evaluate the impact of barrel temperature, screw speed, and residence time on EUD mass average molar mass and IBU release profile, size-exclusion chromatography and dissolution testing were used, respectively. The optimal conditions were established for IBU loadings less than 40 wt. %. For ASD formulations prepared using the ideal variables, spectral and thermal analyses confirmed that, under dry conditions at a temperature of 25°C, IBU remained amorphous during an 18-month storage period. After 28 months, formulations with active pharmaceutical ingredient content above 30 wt. % started to recrystallize. A temperature–composition phase diagram, constructed using melting point depression and glass-transition temperature measurements of IBU–EUD mixtures, correlated well with the long-term physical stability. The effect that minor-to-moderate polymer degradation within the extrudates has on their long-term physical stability and dissolution characteristics is analyzed and discussed.

Hygrothermal conditioning of wet-layup CFRP-concrete adhesive joints modified with silane coupling agent and core-shell rubber nanoparticles

The adhesive bond between externally bonded fiber-reinforced polymer (FRP) repairs and the concrete substrate can significantly deteriorate under hygrothermal conditions. The present study evaluated the epoxy adhesive toughening with core–shell rubber (CSR) nanoparticles and concrete surface functionalization with an epoxy-functional silane coupling agent as a means of improving the bond durability under hygrothermal exposure. To determine the effect of environmental degradation, beam bond test specimens were subjected to control conditions (standard laboratory conditions: 23 ± 2 °C and RH 50 ± 10%) and a hygrothermal accelerated conditioning protocol (ACP) (water immersion at 45 ± 1 °C) for 8 weeks. Bond test results indicate that CSR toughening and silane coupling agent can improve FRP-concrete adhesive bond strength retention following accelerated conditioning by up to 15% over that of neat epoxy. Following accelerated conditioning, CFRP coupons prepared with CSR-modified epoxy retain their mechanical properties, while the CFRP prepared with the neat epoxy exhibited a significant reduction in strength (40%) and elongation (54%). CSR nanoparticles demonstrated good compatibility with the base epoxy resin, as evidenced by differential scanning calorimetry (DSC) glass transition temperature measurements.

Accurate measurement of glass transition temperature of Cu47.5Zr47.5Al5 and Zr41.2Ti13.8Cu12.5Ni10Be22.5 using step-scan modulated differential scanning calorimeter

The onset of the glass transition (Tgonset) and crystallization (Tx) temperatures of Cu47.5Zr47.5Al5 and Zr41.2Ti13.8Cu12.5Ni10Be22.5 (Vitreloy 1) plates were investigated using conventional differential scanning calorimeter (DSC) and step-scan modulated differential scanning calorimeter (MDSC). A large scatter of the Tgonset values with error of ±6.9 K for Cu47.5Zr47.5Al5 and ±8.0 K for Vitreloy 1 have been observed, at a heating rate of 20 K/min using conventional DSC. Such variation is linked with the variation of the enthalpy change of the respective metallic glass up to different extent prior to the glass transition. Our investigation shows that the Tgonset values can be accurately estimated from the reversible heat flow curve with an error of ±0.6 K using step-scan MDSC analysis, which eliminates the effect of enthalpy change near to the glass transition.

Impact of solid state miscibility on quantitive nano-precipitation of budesonide and PVP-VA.

In the present study, the drug–polymer miscibility and molecular interaction of budesonide in polymers (PVP/VA E 735, 635 and 535) systems were studied, by using three techniques including, calculation of Hansen solubility parameters, analysis of melting points depression, and measurement of glass transition temperature (Tg). Budesonide nanoparticles were prepared by sonication technique. The combined effect of four significant formulation variables, namely, polymer and surfactant concentrations, time and amplitude of sonication on particle size, polydispersity, drug loading and entrapment efficiency of drug was investigated by apply 24 factorial design. The drug/ polymer blend was considered miscible depending on the results of three approaches. The results of calculated values of miscibility parameter (χ) for each pair were negative ranging from - 2.012to -1.948. Single Tg and positive deviation from Gordon-Taylor model for all ratios of drug–polymer binary mixtures. Produced amorphous budesonide nanoparticles, depending on choice of polymer and process parameters contained from 97% to 99% drug, with particle size diameter varying in size from 641-357 nm. It was found that clear evidence on effect VA ratio on percent entrapment efficiency and particle size of budesonide.

Heat transfer simulation of the cure of thermoplastic particle interleaf carbon fibre epoxy prepregs

Thermochemical properties are needed to develop process models and define suitable cure cycles to convert thermosetting polymers into rigid glassy materials. Uncertainty surrounding the suitability of thermal analysis techniques and semi-empirical models developed for conventional composite materials has been raised for the new class of particle interleaf materials. This paper describes kinetics, conductivity, heat capacity and glass transition temperature measurements of HexPly® M21 particle interleaf material. Thermal models describing conventional, non-particle epoxy systems were fit to the data and validated through a thick-section cure. Results from curing experiments agree with heat transfer simulation predictions, indicating that established thermal analysis techniques and models can describe polymerisation and evolving material properties during processing of a material representing the class of interleaf toughened systems. A sensitivity study showed time savings up to about 20%, and associated energy-efficiency-productivity benefits can be achieved by using cure simulation for particle interleaf materials.

Ionic liquid modified multiwalled carbon nanotube embedded styrene butadiene rubber membranes for the selective removal of toluene from toluene/methanol mixture via pervaporation

Abstract Present work reports the fabrication of elastomeric membrane based on ionic liquid functionalized multiwalled carbon nanotubes (f-MWCNT) incorporated Styrene butadiene rubber (SBR) for the separation of azeotropic composition of toluene and methanol. The fabricated membranes were characterized by morphological analysis using transmission electron microscopy and glass transition temperature and heat capacity measurements by differential scanning calorimetry. Composite membranes demonstrate impressive separation performance with preferential selectivity towards toluene and 5 phr f-MWCNT loaded membranes was found to show the best result with respect to toluene flux and selectivity. Optimal separation performance with the permeation flux 225% of SBR control membrane and separation factor of 128 (1.6 times of SBR control membrane) is obtained for this membrane. The concurrent optimization of the physical and chemical structures of toluene permeation path on f-MWCNT surface provides the membrane with high-efficiency toluene permeation. Ionic liquid on MWCNT surface confer aromatic pi-pi interaction with toluene molecules leading to greater toluene affinity and higher repellency against methanol. Pervaporation characteristics of the membranes were also strongly influenced by the feed mixture composition. The study confirmed that increasing toluene concentration improved the toluene flux but reduced the separation factor. The experimental pervaporation fluxes were compared with the calculations based on modified Maxwell–Stefan equation. The model allows a good quantitative prediction of experimental flux values.

Using free radical polymerization and Mannich reaction, synthesis and characterization of cationic polyacrylamides having similar molecular weight but different charge densities

Using free radical solution polymerization technique and Mannich reaction, five different polyacrylamides with similar molecular weight but variable charge densities were synthesized. High molecular weight polyacrylamides were synthesized using potassium persulfate and N,N,N',N'-tetramethylethylenediamine system as initiators. This was achieved by increasing the concentration of acrylamide monomer. They were then characterized by infrared spectroscopy, viscosity measurements and glass transition temperature measurement. These compounds with various cationic charge densities from 48.2, 161.7, 355, 425 and 485 C/g were prepared through Mannich reaction. The results indicate, by increasing the acidity of the polyacrylamide solution using sulfuric acid, the pH of the polyacrylamide solution decreases correspondingly. As a result, the positive charges increased resulting in the enrichment of charge densities.

Synthesis and properties of cycloaliphatic epoxy resins containing imide and diphenyl sulfone

A novel variety of cycloaliphatic epoxy resins containing imide and diphenyl sulfone (named as 4,4′-bis[4-(4,5-epoxy-1,2,3,6-tetrahydro-phthalimido) phenoxy] diphenyl sulfone, BIES) is designed and synthesized through the three-step procedure. The mixtures of BIES and diglycidyl 4,5-epoxycyclohexane-1,2-dicarboxylate (TDE-85) are cured with methyl tetrahydrophthalic anhydride. Fourier transform infrared spectrum and proton nuclear magnetic resonance spectrum confirm that the BIES contains the chemical structure of imide and diphenyl sulfone. The measurements of glass transition temperature ( Tg), heat distortion temperature (HDT), and the 5% weight loss temperature ( T5%) show that the co-cured BIES/TDE-85 exhibits excellent heat resistance. For the BIES/TDE-85 with mass ratio of 0.2, Tg, HDT, and T5% of the co-cured epoxy are 175°C, 162°C, and 290°C, respectively. The impact strength increases from 117 J m−1 to 139 J m−1 with the increasing of the mass ratios of the BIES/TDE-85 from 0 to 0.2.

Solid-State NMR Investigation of Drug-Excipient Interactions and Phase Behavior in Indomethacin-Eudragit E Amorphous Solid Dispersions.

To investigate the nature of drug-excipient interactions between indomethacin (IMC) and methacrylate copolymer Eudragit® E (EE) in the amorphous state, and evaluate the effects on formulation and stability of these amorphous systems. Amorphous solid dispersions containing IMC and EE were spray dried with drug loadings from 20% to 90%. PXRD was used to confirm the amorphous nature of the dispersions, and DSC was used to measure glass transition temperatures (Tg). 13C and 15N solid-state NMR was utilized to investigate changes in local structure and protonation state, while 1H T1 and T1ρ relaxation measurements were used to probe miscibility and phase behavior of the dispersions. Tg values for IMC-EE solid dispersions showed significant positive deviations from predicted values in the drug loading range of 40-90%, indicating a relatively strong drug-excipient interaction. 15N solid-state NMR exhibited a change in protonation state of the EE basic amine, with two distinct populations for the EE amine at -360.7ppm (unprotonated) and -344.4ppm (protonated). Additionally, 1H relaxation measurements showed phase separation at high drug load, indicating an amorphous ionic complex and free IMC-rich phase. PXRD data showed all ASDs up to 90% drug load remained physically stable after 2years. 15N solid-state NMR experiments show a change in protonation state of EE, indicating that an ionic complex indeed forms between IMC and EE in amorphous solid dispersions. Phase behavior was determined to exhibit nanoscale phase separation at high drug load between the amorphous ionic complex and excess free IMC.

Properties and Structure of Glassy TeO2 and Binary Potassium and Boron Tellurites

Tellurite glasses show potential for use in mid-infrared optical applications1, but their structure has not been intensively studied. While they do not conduct light better than chalcogenides, which are currently the best glasses for infrared optics, they are much easier to produce. Potassium and boron tellurite glasses, including single component, rapidly cooled TeO2, are reported and studied here. The results include the Glass Transition Temperature (Tg) measurements and Raman spectra. Proposed structural models are also discussed.

A New Method of Constructing a Drug-Polymer Temperature-Composition Phase Diagram Using Hot-Melt Extrusion.

Current experimental methodologies used to determine the thermodynamic solubility of an API within a polymer typically involves establishing the dissolution/melting end point of the crystalline API within a physical mixture or through the use of the glass transition temperature measurement of a demixed amorphous solid dispersion. The measurable "equilibrium" points for solubility are normally well above the glass transition temperature of the system, meaning extrapolation is required to predict the drug solubility at pharmaceutically relevant temperatures. In this manuscript, we argue that the presence of highly viscous polymers in these systems results in experimental data that exhibits an under or overestimated value relative to the true thermodynamic solubility. In previous work, we demonstrated the effects of experimental conditions and their impact on measured and predicted thermodynamic solubility points. In light of current understanding, we have developed a new method to limit error associated with viscosity effects for application in small-scale hot-melt extrusion (HME). In this study, HME was used to generate an intermediate (multiphase) system containing crystalline drug, amorphous drug/polymer-rich regions as well as drug that was molecularly dispersed in polymer. An extended annealing method was used together with high-speed differential scanning calorimetry to accurately determine the upper and lower boundaries of the thermodynamic solubility of a model drug-polymer system (felodipine and Soluplus). Compared to our previously published data, the current results confirmed our hypothesis that the prediction of the liquid-solid curve using dynamic determination of dissolution/melting end point of the crystalline API physical mixture presents an underestimation relative to the thermodynamic solubility point. With this proposed method, we were able to experimentally measure the upper and lower boundaries of the liquid-solid curve for the model system. The relationship between inverse temperature and drug-polymer solubility parameter (χ) remained linear at lower drug loadings. Significantly higher solubility and miscibility between the felodipine-Soluplus system were derived from the new χ values.

Plasma discharge power dependent AC conductivity of plasma poly(ethylene oxide) thin films

Plasma polymerized poly(ethylene oxide) thin film samples with thickness of 500nm were deposited using plasma assisted physical vapour deposition at radio-frequency plasma discharge powers of 0, 2, 5 and 30W, respectively. For comparison, a conventional poly(ethylene oxide) precursor was also investigated. In order to investigate the effect of the plasma discharge power on the cross-linking density of the plasma poly(ethylene oxide) and poly(ethylene oxide) precursors, structural characterization using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy was performed. Structural analysis showed that the density of cross-linking increased upon increasing the plasma discharge power. This increase was observed as an increase in the dynamic glass transition temperature during the DSC measurements. In addition to these characterizations, the dielectric response of the thin film plasma poly(ethylene oxide) samples and poly(ethylene oxide) precursors were measured. The dielectric spectroscopy results showed that changes in the cross-linking density changed the alternative current (AC) conductivity. The measured glass transition temperatures obtained using DSC are in accordance with the glass transition temperatures obtained from the temperature-dependent AC conductivity results. It was observed that the temperature-dependent AC conductivity exhibits Arrhenius behaviour. The activation energies obtained for the plasma polymer samples showed an increase from 0.38eV to 0.5eV upon increasing the plasma discharge power. The plasma discharge power dependent activation energy results also indicate the fragmentation of long polymer chains into more smaller oligomers and radicals occurred upon increasing the plasma power.

A Simple and Sensitive Method for an Important Physical Parameter: Reliable Measurement of Glass Transition Temperature by AIEgens

The glass transition temperature (Tg) is an important physical parameter and signifies the reversible transition process between the glassy state and the rubbery state in polymeric materials. Herein, a simple yet reliable method, denoted as ADEtect, utilizing aggregation-induced emission luminogens (AIEgens) for Tg measurement was developed. The fluorescent images of AIEgen-doped polymer films taken at different temperatures were monitored by a camera under the same settings. By using a MATLAB program, the grayscale of the selected area in each image was calculated. This value decreased steadily with increasing the temperature, and a significant change was observed at Tg. By plotting a graph of the second derivative of relative grayscale against temperature, the Tg of a polymer can be unambiguously determined from the lowest point. The present method shows performance comparable to that of conventional DSC measurement in terms of sensitivity and reliability. Besides, it can measure multiple samples in par...

Sensitization of LnIII (Ln = Eu, Tb, Tm) Ion Luminescence by Functionalized Polycarbonate‐Based Materials and White Light Generation

We prepared pyridine‐2,6‐bis(ethyl)ester [BEP] and pyridine‐2,6‐bis(diethylamide) [BDP] polymers with polycarbonate backbones by ring‐opening polymerization of the pyridine‐bis(ethyl)ester and pyridine‐bis(diethylamide) units appended to a cyclic carbonate via a glycol chain. The polymers were characterized by FTIR, NMR, UV/Vis absorption and fluorescence spectroscopy, as well as SEC, powder XRD, DSC, and TGA. The measured glass transition temperature (Tg) of the BEP polymer was shifted from –32 °C to –7 and –8 °C after coordination of the EuIII and TbIII ions, respectively. Similarly, the Tg of the BDP polymer was shifted from –13 °C to –9 and –10 °C after coordination of EuIII and TbIII ions, respectively. Both polymers sensitized LnIII‐centered emission; the BEP polymer was the most efficient at sensitizing LnIII‐centered luminescence with an emission efficiency of 30 and 31 % for the EuIII and TbIII systems, respectively, compared to the 2 % determined for both the EuIII and TbIII BDP systems. Blue emission was observed when TmIII was used, and a system with the composition BEP1Eu1.8Tb28 led to a material with CIE coordinates (0.31, 0.33), typical of white light.

Process Development and Robust Control of Physical Attributes of an Amorphous Drug Substance

Control of physical attributes of amorphous active pharmaceutical ingredients (APIs) can be challenging due to processability issues, their wide variation during processing and the requirement to control them to specific ranges. In this article, we report our efforts to develop a robust isolation process for boceprevir, which delivers specific surface areas between 3.0 and 9.4 m2/g. We developed mechanistic process understanding by utilizing a new method to measure glass transition temperature of API suspensions. Boceprevir processability and surface area are determined by the interplay between the suspension operating conditions and glass transition temperature. Processing time and thermal history also influence API surface area evolution, rendering a dynamic nature to it. A control strategy was developed consisting of 2 elements: a continuous tee mixer precipitation process, which delivers API in the 40-60 m2/g range and 1 of 2 annealing step variants. In the first, surface area was controlled in 4 batches to 6.7-7.5 m2/g by equilibrating the API suspension above its glass transition temperature and a subsequent vacuum distillation. The second annealing variant controlled surface area to 4.5-6.5 m2/g for over 70 commercial batches through a dynamic vacuum distillation step with prescribed temperature and % batch volume distilled profiles versus time.

Irradiation effect of the insulating materials for fusion superconducting magnets at cryogenic temperature

In ITER, superconducting magnets should be used in such severe environment as high fluence of fast neutron, cryogenic temperature and large electromagnetic forces. Insulating material is one of the most sensitive component to radiation. So radiation resistance on mechanical properties at cryogenic temperature are required for insulating material. The purpose of this study is to evaluate irradiation effect of insulating material at cryogenic temperature by gamma-ray irradiation. Firstly, glass fiber reinforced plastic (GFRP) and hybrid composite were prepared. After irradiation at room temperature (RT) or liquid nitrogen temperature (LNT, 77 K), interlaminar shear strength (ILSS) and glass-transition temperature (Tg) measurement were conducted. It was shown that insulating materials irradiated at room temperature were much degraded than those at cryogenic temperature.

Process development for phenylethynyl-terminated PMDA-type asymmetric polyimide composites

A new type of polyimide, designated TriA X, has been developed for high-temperature composite applications. TriA X is a polymerized monomeric reactant (PMR)-type polyimide derived from 1,2,4,5-benzenetetracarboxylic dianhydride (PMDA), 2-phenyl-4,4′-diaminodiphenyl ether (p-ODA), and phenylethynyl phthalic anhydride (PEPA). The polymer has an asymmetric, nonplanar backbone, resulting in an amorphous structure and high toughness. In this work, a TriA X resin (with degree of polymerization n = 7 in the imide oligomer) was investigated for processability and performance in carbon fiber composites. Rheological measurements were performed on an oligomer with a low degree of imidization to understand the chemo-rheology of the resin system and determine a suitable B-staging temperature. A composite molding cycle was designed, which yielded fully consolidated woven carbon fiber laminates. Void contents in panels produced with this molding cycle were <0.1% as measured by image analysis (IA) of polished sections, and <0.2% as measured by X-ray micro-computed tomography (micro-CT). Matrix-dominated mechanical properties of composites fabricated with the TriA X polymer exceeded those of PMR-15 and AFR-PE-4 composites. These mechanical properties and a measured glass transition temperature of 367°C indicate potential for use of this resin system in high-temperature composites.

Glass transition prediction strategies based on the Couchman-Karasz equation in model confectionary systems

Our objectives were to compare the Couchman-Karasz-predicted glass transition temperature, TCK, to the measured glass transition temperature of a mixture, Tgm, of model confectionary systems and develop an empirical correction to improve the accuracy of prediction. Results showed that the original Couchman-Karasz equation fit the data better than the modified equation; although both generally overestimated Tgm. Blends containing sorbitol had the largest ΔTgmCK, where ΔTgmCK=TCK−Tgm. While Tgm varied with composition, the increase in Tgm with decreasing moisture content was linear (R2¯=0.984) and consistent across blends (4.5 ± 0.9°C/1% moisture, wb). The increase in Tgm with increasing cook temperature was best described by a polynomial model (R2¯=0.998), but adequately described by a more generalizable linear model (R2¯=0.979). Application of an empirical correction based on moisture content or cook temperature and TCK of dry ingredients reduced the average ΔTgmCK from 20.1 °C and 11.3 °C for modified and original equations, respectively, to <5.6 °C.

Melt compounding and characterization of poly(lactide) stereocomplex/natural rubber composites

Poly(lactide) (PLA) is an interesting biodegradable polymer but has limited application because of its brittleness and low thermal stability. We found that both drawbacks of PLA were solved by forming stereocomplexes augmented with natural rubber (NR). Equal amounts of poly(l‐lactide) (PLLA) and poly(d‐lactide) (PDLA) stereoisomers were blended to form a stereocomplex (St‐PLA). Varying amounts of NR (5–30% by weight) were added simultaneously to equal amounts of the stereo isomers by melt blending. FTIR and XRD spectra demonstrated that, despite the added NR, the stereocomplex structures were still generated and complete. Stereocomplex crystallinity decreased with increasing NR content, verified by DSC and XRD, as well as polarizing optical micrographs which showed fewer spherulites at higher NR content. Measured glass transition temperatures (Tg) of St‐PLA/NR blends were significantly lower than for neat St‐PLA, exhibiting shifts to as low as 46°C at 30%wt NR content, because of rubber dispersed in St‐PLA segments expanding the free volume and enhancing chain mobility. Thermal stability of the blends, estimated by TGA, showed desired results, for example, at the 50% weight loss point, the temperature of all St‐PLA/NR blends moved to higher temperatures than neat St‐PLA. POLYM. ENG. SCI., 2017. © 2017 Society of Plastics Engineers