T0034 – Analysis of Thermally Stimulated Current and effect of rubbery annealing around glass-rubber transition temperature in polyethylene terephtalate
Thermally stimulated currents (TSC) in amorphous polyethylene terephthalate films have been investigated in the temperature range of -180 to 140°C. This material shows a very weak intensity peak at approximately -95°C and another around 80°C originated from dipolar process (alpha-peak), as evidenced from the variation of polarizing conditions such as applied electric field and polarizing time. The effect of isochronal rubbery annealing starts to appear from a temperature of annealing of 90°C, it then appears in a TSC spectrum two components around 88 and 108°C allotted, respectively to the true and rigid amorphous phases. The first component tends to disappear in an irreversible way to the detriment of the second which implies the establishment of an order within material during annealing by the formation and growth of nodules. The thermostimulated currents technique allowed to calculate with good precision the activation parameters of each process as well as the evaluation of the crystallinity rate by an established empirical formula.
T0023 – Simulation of thermally stimulated curents in dielectric : effects of thermal expansion
The influence of thermal expansion on thermally stimulated currents has been studied by means of model calculations based on the bistable model of Fröhlich, considering especially the case of materials characterized by expansion coefficients markedly different above and below the relaxation range. A good qualitative and quantitative agreement has been obtained between theory and experiment in elastomeric materials (styrene-isoprene-styrene and isoprene-styrene-isoprene block copolymers) showing that thermal expansion is the main factor responsible for the appearance of current reversals in thermally stimulated polarization processes
T0045 – Characterisation of EVA encapsulant material by thermally stimulated current technique
The purpose of this investigation is to better define the thermal behaviour of EVA-based
encapsulant during photovoltaic module encapsulation process and also in field exposure in
desert climate using the thermally stimulated current (TSC) technique. TSC experiments were
conducted on EVA in the temperature range from -150°C to 70°C, the measurements were
carried out on uncured and cured specimens of EVA and on EVA samples especially prepared
using the laminator equipment. When performing the measurements with the TSC instrument
it was noted that the EVA exhibits two peaks assigned to dipole relaxation processes. The peak
maximum current and the area under the TSC current peak were used for the determination of
the glass transition temperature, activation energy and relaxation frequency. For original
EVA, we found that glass transition temperature at constant polarisation voltage and under
different polarisation temperatures remain unchanged and is located around -38°C. Also, the
activation energy has been determined using initial rise method to be about 0.32 eV. At gel
content of 70%, the cured EVA shows a reduced integrated area under the depolarisation
peak, especially for the high temperature. The combined change in TSC peak parameters of
EVA encapsulant is correlated with the degree of curing.
T0033 – The use of thermal methods for predicting glass-former fragility
Glass-former fragility describes the changing dynamics of a supercooled liquid with temperature and so dictates the temperature of glass transition as well as the dynamics of the non-equilibrium glassy state. Fragility parameters can be calculated from either experimental relaxation time or viscosity data. Predictions of fragility can also be made using thermal methods. The objectives of this manuscript are to evaluate three thermal methods of fragility prediction and, using these methods, to predict the fragility of a number of pharmaceutical glass-formers.
Using differential scanning calorimetry, fragility predictions were performed by extrapolating configurational entropy to zero and by calculating an activation enthalpy of structural relaxation at the glass transition (?ETg) from the scanning rate dependency of the glass transition temperature, and glass transition width. On comparison with experimental Vogel-Tammann-Fulcher (VTF) fragility parameters for four glass-formers, all thermal methods were found to have reasonable predictive ability. Characterisation of pharmaceutical glass-formers by all thermal methods yielded predicted VTF D parameters in the range of 7-15. Predictions for a further 10 pharmaceutical glass-formers using only the configurational entropy method were within this range suggesting that moderately 'fragile' behaviour may be a common feature of such materials.
T0022 – Thermally Stimulated Currents from corona-charged polypropylene films : a thermal effect of vacuum deposition of metallic electrodes
It is demonstrated that the thermally stimulated currents (TSC) from positively or negatively corona-charged polypropylene strongly depend on the order of the following two processes: a process of vacuum deposition of Al electrodes on the sample polymer and a process of heat-treatment of the polymer. Observed results are explained by a thermal effect which is introduced during the vacuum deposition of metallic electrodes. This thermal effect of the vacuum deposition of metallic electrodes is the largest for Al and the smallest for Bi among Al, Au, Ag, and Bi. Observed TSC spectra have three peaks at about 68, 142, and above 147°C for positively charged samples and four peaks at about 48, 90, 142, and above 147°C for negatively charged samples, respectively. Origins of these TSC peaks are discussed in some detail.
T0044 – A mechanistic investigation of an amorphous pharmaceutical and its solid dispersions. Part II: Molecular mobility and activation thermodynamic parameters
The ability of TSDC to characterize further amorphous
materials beyond that possible with DSC was presented in part I (16)
of this work. The purpose of part II presented here is to detect and
quantitatively characterize time-scales of molecular motions (relaxation
times) in amorphous solids at and below the glass transition
temperature, to determine distributions of relaxation times associated
with different modes of molecular mobility and their temperature
dependence, and to determine experimentally the impact upon
these parameters of combining the drug with excipients (i.e., solid
dispersions at different drug to polymer ratios). The knowledge
gleaned may be applied toward a more realistic correlation with physical
stability of an amorphous drug within a formulation during storage.
Methods. Preparation of amorphous drug and its solid dispersions
with PVPK-30 was described in part I (16). Molecular mobility and
dynamics of glass transition for these systems were studied using
TSDC in the thermal windowing mode.
Results. Relaxation maps and thermodynamic activation parameters
show the effect of formulating the drug in a solid dispersion on converting
the system (drug alone) from one with a wide distribution of
motional processes extending over a wide temperature range at and
below Tg to one that is homogeneous with very few modes of motion
(20% dispersion) that becomes increasingly less homogeneous as the
drug load increases (40% dispersion). This is confirmed by the high
activation enthalpy (due to extensive intra- and intermolecular interactions)
as well as high activation entropy (due to higher extent of
freedom) for the drug alone vs. a close to an ideal system (lower
enthalpy), with less extent of freedom (low entropy) especially for the
20% dispersion. The polymer PVPK-30 exhibited two distinct modes
of motion, one with higher values of activation enthalpies and entropy
corresponding to -relaxations, the other with lower values
corresponding to -relaxations characterized by local noncooperative
Conclusions. Using thermal windowing, a distribution of temperature-
dependent relaxation times encountered in real systems was obtained
as opposed to a single average value routinely acquired by
other techniques. Relevant kinetic parameters were obtained and
used in mechanistically delineating the effects on molecular mobility
of temperature and incorporating the drug in a polymer. This allows
for appropriate choices to be made regarding drug loading, storage
temperature, and type of polymer that would realistically correlate to
T0032 – Characterization of structural heterogeneity of polyurethane coatings
The thermal analysis techniques - Differential Scanning Calorimetry and ThermoStimulated Current - have been used to characterize a polyurethane high solid coating. The glass transition temperature, as determined by DSC, is 60°C. Below this glass transition temperature, an sub dielectric relaxation mode has been observed; it corresponds to cooperative movements precursor of the glass transition. The ss dielectric relaxation mode, located at Tg has been attributed to movements of soft sequences of the amorphous phase liberated at the glass transition temperature. The analysis of the fine structure shows that they are constituted of elementary processes characterized by relaxation times following a compensation law. Above Tg, the hs dielectric relaxation of hard sequences has been shown. It corresponds to hard sequences hydrogen bonded in polyurethane
T0021 – Dielectric relaxation phenomena in PEEK
Molecular movements in poly(ether-ether-ketone) have been investigated by thermally stimulated currents (TSC). The TSC spectra have been analyzed as a function of crystallinity. Around -80°C, two sub-modes are observed: the lower temperature sub-mode has been attributed to localized cooperative movements in the crystallizable amorphous phase; and the upper temperature sub-mode has been located in the crystalline phase. The magnitude of the corresponding compensation line increases with the ratio of crystallinity. Around the glass transition temperature (145°C), the existence of two sub-modes has been shown: the lower temperature sub-mode has been attributed to the dielectric manifestation of the glass transition and the cooperative movements have been assigned to the "true amorphous region" of PEEK; the upper temperature sub-mode is dependant upon crystallinity. Regardless of the preceding sub-mode, the activation enthalpies of the constituting elementary processes are practically constant. This sub-mode has been attributed to the "rigid amorphous region", constrained by the crystallites.
T0043 – A mechanistic investigation of an amorphous pharmaceutical and its solid dispersions. Part I: A comparative analysis by Thermally Stimulated Depolarization Current and Differential Scanning Calorimetry
To explore using thermally stimulated depolarization current
(TSDC), in comparison to differential scanning calorimetry
(DSC), for the characterization of molecular mobility of an amorphous
pharmaceutical new chemical entity (LAB687), an amorphous
polymer (PVPK-30), and their combination as solid dispersions at
different % drug loadings.
Methods. Amorphous drug was prepared by quenching from the
melt. Solid dispersions containing 10-60% of drug in polymer were
prepared by solvent evaporation method. Glass transition temperatures
(Tg) were determined by DSC and TSDC.
Results. In comparison to a single Tg obtained from DSC for the drug
substance, TSDC shows two overlapping relaxations. Both peaks correspond
to -relaxations that are associated with the glass transition,
with the second peak corresponding to the rigid fraction that is difficult
to be detected by DSC because it is associated with only small
changes in heat capacity. Two overlapping relaxations were also observed
for the polymer vs. one Tg by DSC. The lower temperature
relaxation is believed to be a beta-relaxation, whereas the higher temperature
transition corresponds to an alpha-relaxation. For the solid dispersions,
one single peak was obtained for each of the 20% and 30%
dispersions in excellent agreement with the DSC results. However, at
the 40% drug load, a small shoulder was observed by TSDC at the
low temperature of the main peak. This shoulder becomes more pronounced
and overlaps with the main peak as the drug load increases
to 50% and 60%. Agreement between the Tg values calculated by the
Gordon-Taylor equation and the DSC and TSDC experimental data,
especially for the 20% and 30% drug loading, indicate ideal miscibility.
At higher drug loads, only by TSDC was it possible to detect the
saturation level of the drug in the polymer.
Conclusions. TSDC proved to be very sensitive in detecting small
reorientational motions in solids and in separating overlapping events
with only slight differences in molecular motion exhibited as broad
events in DSC. This allowed for detection of the rigid fraction of the
amorphous drug, the sub-glass transition beta-relaxation in the polymer,
and the limit of miscibility between the drug and the polymer in the
T0031 – Study of molecular mobility at the secondary relaxations range in polyamide 66 and polyamide 66/EPR blends by thermally stimulatde creep and current
Thermally stimulated creep with fractional loading technique and thermally stimulated current have been used to investigate the relaxation processes of polyamide 66 and polyamide 66/EPR blends over temperature range covering y, beta and alpha-EPR. Absorbed water decreases the thermally stimulated creep and the thermally stimulated current height of y-relaxation. The thermally stimulated creep mechanical beta-relaxation in PA66 is characterized by a broad peak, while the thermally stimulated current dielectric one is composed of two separate processes beta1 and beta2 according to the maximum temperature decrease. The peak height of the beta1 component is increased by moisture while the beta2 component is not modified. According to the criteria of Starkweather for sample and complex relaxations, the y- and low temperature part of beta-relaxations have been assigned to localized non-cooperative motions. The high temperature part of beta-process and alpha-EPR-relaxation have positive activation entropies and result from high cooperative motions. These interpretations from thermal sampling analysis is in close aggrement with the predictions of Ngai's coupling model.
T0020 – Influence of the crystalline phase on the molecular mobility of PVDF
Thermostimulated current (TSC) spectroscopy was applied to the characterization of dielectric relaxations associated with the glass transition of a series of P(VDF/TrFE) copolymers. The maximum temperature of the -mode increases slightly as the TrFE unit content is increased, in the same manner as the glass transition temperature. By using the technique of fractional polarizations to the resolution of this relaxation mode, we have isolated, for all the polymers investigated, a series of elementary relaxation times that obey a compensation law. This behavior is characteristic of the free amorphous phase of polymers. The mean activation energy of this mode increases as the TrFE unit content is increased, due to a stiffening of molecular chains. Annealing of the copolymers above their ferroelectric-to-paraelectric transition induces a strong crystallinity increase of the materials. As a matter of fact, the amorphous phase is squeezed in to dimensions lower than the characteristic length scale associated with the glass transition
T0041 – Detection of low levels of the amorphous phase in crystalline pharmaceutical materials by Thermally Stimulated Current Spectrometry
To demonstrate the applicability of thermally stimulated
current (TSC) spectrometry for the detection of low levels of the
amorphous phase in crystalline pharmaceutical materials.
Methods. A crystalline drug substance was melt quenched to produce
an amorphous material. Blends of the crystalline and amorphous
phases in different ratios (from 75:25 to 99:01) were prepared by
serial dilution. TSC studies were performed by applying an electric
field at a temperature above the glass transition temperature (Tg) to
orient the dipoles, rapidly cooling to 0°C, short circuiting for 1 min,
and scanning at 7°C/min to measure the depolarization current. The
temperature of the peak in the spectrum corresponds to the Tg of the
amorphous phase. Modulated differential scanning calorimtery
(DSC) studies were performed using three different test protocols
(varying linear heating rate, modulation amplitude, and time period).
Powder X-ray diffraction (XRD) studies were performed using a
Siemens D500 diffractometer.
Results. The ability to detect the amorphous phase by powder XRD
is beset with problems due to indirect inference, orientation effects,
and instrument-related intensity variations. Even using a consistent
sampling procedure and an internal standard, the XRD could quantify
the amorphous phase at a level of 5%. In the conventional or
modulated DSC, the amorphous phase manifests itself as a shift in the
baseline. Using modulated DSC it was possible to detect the amorphous
phase at a level of 5% when tested at a heating rate of 2°C/min
and an amplitude of ±1.0°C with a period of 30 s. The moisture
sorption method appears to have a similar detection capability. In
TSC scans, the glass transition event due to molecular/segmental mobility
in the amorphous phase was manifested as a peak/shoulder on
the low-temperature side of the depolarization peak of the crystalline
phase. The amorphous phase was unambiguously detected at 2%
with a lower detection limit of ~1%.
Conclusions. On the basis of the results of this preliminary investigation,
TSC appears to be capable of detecting the amorphous phase
at as low as ~1% in crystalline pharmaceuticals, thus offering a much
needed capability in discerning factors.
T0030 – Ultra low frequency study of dielectric relaxation in ferroelectric Polyamide 11
T0019 – Low-loss behavior of alpha-PVDF
The exact nature of the polarization processes in low-loss materials is not sufficiently understood and good experimental material is relatively scarce. Dielectric response of alpha-PVDF covering 8.5 decades of frequency between 10^(-2) and 3x10^6 Hz and a range of temperatures between 103 and 138 K were analyzed to reveal the nature of the dominant polarization process. Correcting for a series resistance and a Debye-like loss process at 50 kHz, the 'universal' fractional power law of dielectric response is well maintained, the residual tan delta falls between 0.002 and 0.02 depending on temperature and frequency, with the residual loss process presumed to be due to hopping charge carriers having an activation energy of 0.035 eV. The universal process itself has a relatively high loss but its amplitude is low and this accounts for the low tan delta
T0040 – The thermal analysis of films in the 21st century: Relevance to cell culture, biochips and roll-to-roll circuits
Films may be considered as wide fibers, or as unique material geometry possessing two dimensional symmetry (X, Y, Z). Potentially different uniformity issues along the machine (long) and transverse directions of the film, characterization of Z-axis performance-especially as films become "thin" and the characterization/identification of surface modification, introduce the need for careful sampling strategies if the resulting thermal analysis data is to be reflective of either process history or end-use performance or both. Two dimensional imaging by a combination of techniques-i.e., DSC-WAXS-FTIR-AFM exploit the convenience of the sample geometry, while aiding in the definition of structural complexity. Molecular spectroscopy techniques (DMA, TSC) provide a sensitive and instructive tool for examining novel surface or interface chemistry. Characterization under biorelevant conditions (37°C, aqueous, standard saline, presence of adhesive and other proteins, presence of cells) is critical for the generation of meaningful data on films to be utilized biologically (cell culture, tissue engineering substrates, biochips). Of special interest are strategies for accelerated aging that allow prediction of biological or biorelevant performance.
T0029 – Thermal behavior of ferroelectric polyamide 11 in a relation to pyroelectric properties
The pyroelectric properties of oriented thin films of ferroelectric Polyamide 11 have been studied in the temperature range of -100°C up to +140°C. The temperature dependence of the experimental pyroelectric coefficient has been analyzed. Three changes of slope of the pyroelectric coefficient are observed at -20, +50, and +100°C. The origin of the lower temperature event has not yet been defined. The upper transition is attributed to chain movements in crystalline regions, and more precisely, to a crystalline phase transition. The intermediate event is close to the glass transition temperature Tg observed by DSC. It is attributed to the manifestation of the glass transition. Below Tg, the variations of the pyroelectric coefficient are very small. For higher temperatures, it increases rapidly, attesting to a major contribution of secondary pyroelectricity and dimensional effects above Tg. The breaking of hydrogen bonds occurring at the glass transition temperature observed on DSC thermograms does not affect pyroelectric properties. Pyroelectric properties are mildly reduced after annealing at temperatures up to +140°C. A comparative study of oriented ferroelectric films prepared by quenching from the melt and nonoriented slowly cooled samples has been carried out by means of DSC
T0018 – Dielectric relaxation properties of filled ethylene propylene rubber
Thermally stimulated discharge currents and time domain dielectric spectroscopy were employed to characterize the behavior of clay-filled ethylene propylene rubber. Measurements were made on samples with different clay concentrations and particle sizes. The main effect of the clay filler on the electrical properties is on interfacial polarization which occurs at the clay polymer interface. The experimental results are sensitive to the shape of the clay particles. A few results indicate that other mechanisms also affect the electrical behavior of this material
T0039 – Thermal behaviour and slow molecular mobility in two isomers of biphenylmethanol DSC and TSDC study
The thermal behaviour of 2- and 4-biphenylmethanol were studied by differential scanning calorimetry (DSC). It was found that the 2-isomer shows a relatively strong resistance to crystallisation, and that it easily vitrifies on cooling. Oppositely, 4-biphenylmethanol readily crystallizes on cooling. The slow molecular mobility of 2-biphenylmethanol in the amorphous solid state was studied by DSC and by thermally stimulated depolarisation currents (TSDC). Both techniques indicate that 2-biphenylmethanol is a relatively strong glass-former, with a fragility index of ~50 in the Angell's scale.
T0028 – Effect of water on the molecular mobility of elastin
Purified and hydrated elastin is studied by both thermal and dielectric techniques to have insight into the chain dynamics of this protein. By differential scanning calorimetry, the glassy behavior of elastin is highlighted; the glass transition temperature (Tg) of elastin is found to be widely dependent on hydration, falling from 200°C in the dehydrated state to 30°C for 30% hydration. A limit of Tg at around 0°C is found when crystallizable water is present in the system, that is, when the formation of ice prevents motions of some 10 nm along the polypeptidic chains. The technique of thermally stimulated currents, carried out in the -180 to 0°C temperature range, is useful to detect localized motions. In this case, too, the localized motions vary considerably according to hydration: a first relaxation mode is observed at -145°C and it is associated with the reorientation of crystallizable water in ice I; a second relaxation mode, more complex and cooperative, occurs at around -80°C and could be attributed to the complex constituted by the dipolar groups of the polypeptidic chain and noncrystallizable water, behaving as a glassy system
T0017 – Origins of Thermally Stimulated Current in polyethersulfone
In order to understand the dominant carrier species in electrical conduction in polyethersulfone (PES), thermally stimulated current (TSC) measurements were carried out under various conditions. It was found that PES has two TSC peaks in the temperature range from 20 to 220°C, consisting of an alpha peak at ~210°C and a beta peak whose peak temperature moves towards a higher temperature with an increasing poling temperature. Even when the sample was not poled, PES shows a spontaneous current with its peak at ~210°C. Both the spontaneous current peak and the alpha peak were found to disappear when the sample had been heated to 230°C, keeping the external circuit closed. From such similarity of appearance and disappearance between the two peaks, it is concluded that they have the same origin. From the change in the spatial distribution of space charges inside the sample measured simultaneously with the TSC measurements, positive charges, probably due to K+ ions, existed nonuniformly in the sample from the beginning, and are thought to be responsible for the two peaks. From a similar study, the beta peak is considered to be due to polarization of ionic space charges during the poling process
T0038 – Intrinsic compensation phenomenon in thermally stimulated depolarisation studies
The compensation behaviour as observed in thermally stimulated depolarisation currents (TSDC) corresponds to the linear relationship found between the Arrhenius (or Eyring) apparent thermokinetic parameters obtained in a series of thermal sampling (TS) experiments performed in the region of cooperative relaxation processes, particularly around the glass transition of glass forming materials. The compensation effect exhibits the same features of the intrinsic compensation found for any given TS curve, where the values of Ea and t0, in the region where the sum of square residues is low, are highly correlated, being this correlation similar to the conventional compensation. This intrinsic compensation is a result, and exhibits the same features, of the compensation found in the description of a given set of points obtained with the Arrhenius equation with the own Arrhenius equation. This compensation is transmitted directly to the equation that describes the temperature dependence of the depolarisation currents, J(T), as a nearly direct relationship exists between J(T) and t(T). In fact, it was shown that J(T) for an elementary process could be approximated by P0 exp[-c/t(T)]/t(T), c being a constant.
T0027 – Relaxations in amorphous and semi-crystalline polyesters. A study by thermally stimulated depolarization currents
Thermally stimulated depolarization currents and differential scanning calorimetry are performed on thermoplastic polyesters to characterize both and relaxations. The influence on the different relaxations phenomena of the chemical structure (size of the naphthalene groups, presence of cyclohexane, length of the aliphatic group, ) as well as the influence of the crystallinity are discussed. The three phases model with a crystalline part, a rigid amorphous part unable to relax and an amorphous phase able to relax at various temperatures depending on the distribution of the relaxation times is used to explain the evolution of the main relaxation while the standard two-phases model is sufficient to explain the variations of the relaxation mode. Elementary analysis of both and relaxations show that the relaxation characterized by a continuous variation of activation energies as a function of temperature follows the activated state equation with a zero activation entropy while the cooperative a relaxation exhibits a prominent maximum of the activation energies at the glass transition temperature.
T0016 – Analysis of the experimental distribution of relaxation times around the liquid-glass transition of poly(vinylidene fluoride)
The dielectric relaxation mode associated with the liquid-glass transition of a semicrystalline polymer, polyvinylidene fluoride, has been analyzed by the technique of fractional polarizations. A discrete distribution of relaxation times following an Arrhenius law has been obtained experimentally. The activation energy of the "single'' relaxation processes are distributed according to a Gaussian function. Moreover, these relaxation times follow a compensation law. These results allowed us to introduce a continuous distribution of relaxation times whose parameters are temperature dependent. The validity of the method was verified for the thermally stimulated current spectra. Use is made of this distribution to compute the temperature and frequency dependence of the complex dielectric permittivity.
T0037 – Weak solid-solid transitions in pharmaceutical crystalline solids detected via thermally stimulated current
To demonstrate the ability of thermally stimulated current (TSC), normally used to study amorphous systems, in detecting weak solid-solid transitions in crystalline pharmaceutical compound. Methods: Polymorphs of a new chemical entity, LAU254, were generated and characterized using conventional and hot plate X-ray diffraction, DSC and TSC. Equilibration of 50:50 mixtures of the different polymorphs and solubility studies were conducted in aqueous and organic solvent at 25 and 50°C and then analyzed by X-ray and DSC. Results: Four crystalline forms (A-D) were isolated. Form B showed one single endotherm at 180°C while the other forms showed lower melting endotherms, a crystallization exotherm and eventually a final melting endotherm corresponding to that of form B (180°C). The heat of fusion of form B was the highest. In contrast, solubility as well as mixture equilibration studies resulted in all forms converting to form A. TSC analysis revealed a well-defined reproducible peak with a maximum at 130°C which was suspected to be a solid-solid transition. This was confirmed by hot plate X-ray diffraction where careful probing around 120-130°C revealed three different forms; form A (the initial form), a second form that appears above 150°C, melts, crystallizes and produces form B. Careful inspection of larger sample sizes in DSC showed a small endotherm at 130°C. Conclusions: TSC, normally used to study amorphous systems, proved to be useful in detecting weak solid-solid transitions in crystalline pharmaceuticals, an application that has never been explored or reported previously. This resulted in identifying a form, obtainable only at temperatures above the transition temperature (related enantiotropically to the form that is most stable at ambient temperatures) and in reconciling the DSC and solubility data. TSC can be very useful in detecting and probing those transitions that occur in the solid state due to subtle dipolar motion and are not associated with large changes in global motion and heat capacity that is needed for detection by DSC and therefore can be complementary to DSC in obtaining a more complete assessment of the polymorphism behavior of crystalline solids.
T0026 – Thermally stimulated measurements on polycrystalline Pbl2 layers
Thermally stimulated current measurements have been performed on polycrystalline layers of lead iodide grown from solution. Several TSC peaks or bands have been observed at temperatures of 100 K, 195-220 K, 230-240 K and 270-300 K. Comparison with PbI 2 single crystal shows that the polycrystalline structure of the material introduces additional defects. In contrast the defect currently found in single crystal and attributed to the lead vacancy has not been clearly evidenced in the polycrystalline layers. The position and relative intensity of the peaks can be modified by Ag doping and thermal annealing. On the other hand, only small differences resulting from the anisotropy of the material have been observed depending on the orientation of the electric field with regards to the grains orientation.
T0048 – Weak solid–solid transitions in pharmaceutical crystalline solids detected via thermally stimulated current
To demonstrate the ability of thermally stimulated current (TSC), normally used to study amorphous systems, in detecting weak
solid–solid transitions in crystalline pharmaceutical compound. Methods: Polymorphs of a new chemical entity, LAU254, were generated and
characterized using conventional and hot plate X-ray diffraction, DSC and TSC. Equilibration of 50:50 mixtures of the different polymorphs
and solubility studies were conducted in aqueous and organic solvent at 25 and 50 ?C and then analyzed by X-ray and DSC. Results: Four
crystalline forms (A–D) were isolated. formBshowed one single endotherm at 180 ?Cwhile the other forms showed lower melting endotherms,
a crystallization exotherm and eventually a final melting endotherm corresponding to that of form B (180 ?C). The heat of fusion of form B was
the highest. In contrast, solubility as well as mixture equilibration studies resulted in all forms converting to form A. TSC analysis revealed a
well-defined reproducible peak with a maximum at ?130 ?C which was suspected to be a solid–solid transition. This was confirmed by hot
plate X-ray diffraction where careful probing around 120–130 ?C revealed three different forms; form A (the initial form), a second form that
appears above 150 ?C, melts, crystallizes and produces form B. Careful inspection of larger sample sizes in DSC showed a small endotherm
at ?130 ?C. Conclusions: TSC, normally used to study amorphous systems, proved to be useful in detecting weak solid–solid transitions in
crystalline pharmaceuticals, an application that has never been explored or reported previously. This resulted in identifying a form, obtainable
only at temperatures above the transition temperature (related enantiotropically to the form that is most stable at ambient temperatures) and
in reconciling the DSC and solubility data. TSC can be very useful in detecting and probing those transitions that occur in the solid state due
to subtle dipolar motion and are not associated with large changes in global motion and heat capacity that is needed for detection by DSC and
therefore can be complementary to DSC in obtaining a more complete assessment of the polymorphism behavior of crystalline solids.
T0047 – Thermal analysis of complex relaxation processes in poly(desaminotyrosyl-tyrosine arylates)
The goal of this study is to better understand the thermal characteristics and molecular behavior of two poly(desaminotyrosyl-tyrosine arylates).
These two polymers were chosen from a combinatorial library of polymers developed by changing the type and size of the two substitutable
chain locations. The objective of this work was to describe the origin of the complex relaxation processes that have been observed
by thermal analysis methods. DSC, TMA and TSC studies were conducted on poly(desaminotyrosyl-tyrosine dodecyl dodecanedioate), poly(DT
12,10), and poly(desaminotyrosyl-tyrosine ethyl succinate), poly(DT 2,2), in film and fiber form. DSC experiments on poly(DT 2,2) show only
a glass transition at about 80°C which is characteristic of an amorphous polymer. The DSC of poly(DT 12,10) shows multiple thermal events
indicative of a more complex internal structure. The thermally stimulated current (TSC) analysis results for poly(DT 2,2) indicate a region of
molecular mobility at about 80°C consistent with the Tg from DSC. For poly(DT 12,10) there is a dipole relaxation process observed at about
40°C. An additional region of mobility at 60°C for poly(DT 12,10) fibers is observed. The comparison of conventional TSC with a modified
TSC procedure suggests that this process represents a spontaneous reorganization of the internal structure of the solid. The comparison of DSC
and TSC results suggests that poly(DT 12,10) has two distinct modes of organization with a transition between these modes at about 60°C.
Previously published results indicate that solid state structure formation is related to two different modes of hydrogen bonding in the internal
structure of the solid.
T0052 – Comparison of HPMC based polymers performance as carriers for manufacture of solid dispersions using the melt extruder
Preparation of amorphous solid dispersions using hot-melt extrusion process for poorly water soluble compounds which degrade on melting remains a challenge due to exposure to high temperatures. The aim of this study was to develop a physically and chemically stable amorphous solid dispersion of a poorly water-soluble compound, NVS981, which is highly thermal sensitive and degrades upon melting at 165 °C. Hydroxypropyl Methyl Cellulose (HPMC) based polymers; HPMC 3cps, HPMC phthalate (HPMCP) and HPMC acetyl succinate (HPMCAS) were selected as carriers to prepare solid dispersions using hot melt extrusion because of their relatively low glass transition temperatures. The solid dispersions were compared for their ease of manufacturing, physical stability such as recrystallization potential, phase separation, molecular mobility and enhancement of drug dissolution. Two different drug loads of 20 and 50% (w/w) were studied in each polymer system. It was interesting to note that solid dispersions with 50% (w/w) drug load were easier to process in the melt extruder compared to 20% (w/w) drug load in all three carriers, which was attributed to the plasticizing behavior of the drug substance. Upon storage at accelerated stability conditions, no phase separation was observed in HPMC 3cps and HPMCAS solid dispersions at the lower and higher drug load, whereas for HPMCP, phase separation was observed at higher drug load after 3 months. The pharmaceutical performance of these solid dispersions was evaluated by studying drug dissolution in pH 6.8 phosphate buffer. Drug release from solid dispersion prepared from polymers used for enteric coating, i.e. HPMCP and HPMCAS was faster compared with the water soluble polymer HPMC 3cps. In conclusion, of the 3 polymers studied for preparing solid dispersions of thermally sensitive compound using hot melt extrusion, HPMCAS was found to be the most promising as it was easily processible and provided stable solid dispersions with enhanced dissolution.
T0051 – Self-assembling peptide-enriched electrospun polycaprolactone scaffolds promote the h-osteoblast adhesion and modulate differentiation-associated gene expression
Electrospun polycaprolactone (PCL) is able to support the adhesion and growth of h-osteoblasts and to delay their degradation rate to a greater extent with respect to other polyesters. The drawbacks linked to its employment in regenerative medicine arise fromits hydrophobic nature and the lack of biochemical signals linked to it. This work reports on the attempt to add five different self-assembling (SA) peptides to PCL solutions before electrospinning. The hybrid scaffolds obtained had regular fibers (SEM analysis) whose diameters were similar to those of the extracellularmatrix, more stable hydrophilic (contact angle measurement) surfaces, and anamorphous phase constrained by peptides (DSC analysis). They appeared to have a notable capacity to promote the h-osteoblast adhesion and differentiation process by increasing the gene expression of alkaline phosphatase, bone sialoprotein, and osteopontin. Adding an Arg-Gly-Asp (RGD) motif to a self-assembling sequence was found to enhance cell adhesion, while the same motif condensed with a scrambled sequence did not, indicating that there is a cooperative effect between RGD and 3D architecture created by the self-assembling peptides. The study demonstrates that self-assembling peptide scaffolds are still able to promote beneficial effects on h-osteoblasts even after they have been included in electrospun polycaprolactone. The possibility of linking biochemical messages to self-assembling peptides could lead the way to a 3D decoration of fibrous scaffolds.
T0050 – Local motions in L-iditol glass: Identifying different types of secondary relaxations
The sub-Tg relaxations in amorphous L-iditol have been studied by Thermally Stimulated Depolarisation Current (TSDC). The effect of aging on these motional processes was analyzed during annealing at 253K and 243K, respectively 19K and 29K below its calorimetric glass tranaition at Tg=272K.
T0049 – The nature of crystal disorder in milled pharmaceutical materials
The purpose of this study was to study the nature of disorder in milled crystalline materials. Specifically to elucidate if the induced disorder represents crystal defects or amorphous regions. Felodipine and griseofulvin were chosen as model drugs and subjected to milling. Cryomilling was chosen in order to mitigate the influence of heat generated by the process. Amorphous drug samples were produced by quenching the melt. Crystalline, amorphous and cryomilled drug samples were characterized by powder X-ray diffraction (PXRD), thermal analysis (DSC), thermal polarization (thermally stimulated polarization current), and surface energy (inverse gas chromatography). The PXRD analysis shows that cryomilling reduces the crystallinity of the two drugs, while maintaining the same crystal form. Heat capacity measurements (DSC) show that milled material for either drug does not exhibit a glass transition but shows instead an exothermic (crystallization like) event. The thermal polarization profiles revealed that none of the modes of molecular motion (polarization peaks) characteristic of the amorphous formwere observed
in either the unmilled crystalline or milled forms for either drug. For each drug, the polarization spectra of milled forms were similar, but not identical, to those of the corresponding unmilled crystalline materials. Inverse gas chromatography (IGC) measurements showed that the surface energy of cryomilled samples was higher than those of the unmilled and amorphous forms for both drugs. The polarization and heat capacity measurements show that the disorder induced by milling either griseofulvin or folodipine consists of crystal defects rather than amorphous regions. The exothermic event in the milled samples is attributed to the crystallization of defects in the crystal. These results when combined with the IGC measurements
indicate that the milled material retains its crystalline character, making it more stable (at the core) than the amorphous form. However, the milled material has also the most active surface, making itthe more interactive with other surfaces as an activated powder.