The Activation Energy at T g and the Fragility Index of Indomethacin,Predicted from the Influence of the Heating Rate on the Temperature Position and on the Intensity of Thermally Stimulated Depolarization Current Peak

Purpose. The purpose of this study was to estimate the activation energy at the glass transition temperature (and the fragility index) of amorphous indomethacin from the influence of heating rate on the features of the relaxation peaks obtained by thermally stimulated depolarization currents (TSDC) and to compare the obtained results with those obtained by other procedures based on TSDC data. Methods. The glass transition temperature region of amorphous indomethacin was characterized at different heating rates by TSDC in a way similar to that used to determine the kinetics of the glass transition relaxation by differential scanning calorimetry. The features of a thermal sampled TSDC peak, namely the temperature location and the intensity, depend on the heating rate. Results. The activation energy for structural relaxation (directly related to glass fragility) was estimated from the heating rate dependence of the TSDC peak location, T _m, and of the maximum intensity of the TSDC peak, I(T _m). Conclusions. The methods for determining the activation energy for structural relaxation and fragility of indomethacin from TSDC data obtained with different heating rates were compared with other procedures previously proposed. TSDC, which is not a very familiar technique in the community of pharmaceutical scientists, proved to be a very convenient technique to study molecular mobility and to determine the fragility index in glass-forming systems. The value of 60 appears as a reasonable value of the fragility index of indomethacin.     

A Pragmatic Test of a Simple Calorimetric Method for Determining the Fragility of Some Amorphous Pharmaceutical Materials

Purpose. To evaluate a simple calorimetric method for estimating the fragility of amorphous pharmaceutical materials from the width of the glass transition region. Methods. The glass transition temperature regions of eleven amorphous pharmaceutical materials were characterized at six different heating and cooling rates by differential scanning calorimetry (DSC). Results. Activation energies for structural relaxation (which are directly related to glass fragility) were estimated from the scan rate dependence of the glass transition temperature, and correlations between the glass transition widths and the activation energies were examined. The expected correlations were observed, and the exact nature of the relationship varied according to the type of material under consideration. Conclusions. The proposed method of determining the fragility of amorphous materials from the results of simple DSC experiments has some utility, although "calibration of the method for each type of materials is necessary. Further work is required to establish the nature of the relationships for a broad range of amorphous pharmaceutical materials.     

TSDC and DSC Investigation on the Molecular Mobility in the Amorphous Solid State and in the Glass Transformation Region of Two Benzodiazepine Derivatives: Diazepam and Nordazepam

In this work we study the molecular mobility in the amorphous solid state and in the glass transformation region of two compounds, diazepam and nordazepam; these are two benzodiazepines, a family of psychotropic drugs with sedative, anxiolytic and muscle-relaxing properties. The experimental techniques used are thermostimulated currents (TSC) and differential scanning calorimetry (DSC). TSC is a time-dependent technique recognized for its high resolving power; the use of this technique in the depolarization and polarization modes (TSDC and TSPC respectively), provides results that confirm and complement results of dielectric relaxation spectroscopy (DRS) published recently. On the other hand, the variation with the heating rate of the temperature position of the DSC glass transition signal also allowed the estimation of the activation energy at T_g and of the dynamic fragility of the two glass formers.     

Molecular Mobility in Raffinose in the Crystalline Pentahydrate Form and in the Amorphous Anhydrous Form

Purpose The aims of the study are to characterize the slow molecular mobility in solid raffinose in the crystalline pentahydrate form, as well as in the anhydrous amorphous form (T_g = 109°C at 5°C/min), and to analyze the differences and the similarities of the molecular motions in both forms.Methods Thermally stimulated depolarization current (TSDC) is used to isolate the individual modes of motion present in raffinose, in the temperature range between −165 and +60°C. From the experimental output of the TSDC experiments, the kinetic parameters associated with the different relaxational modes of motion were obtained, which allowed a detailed characterization of the distribution of relaxation times of the complex relaxations observed in raffinose. The features of the glass transition relaxation in raffinose were characterized by differential scanning calorimetry (DSC).Results A complex mobility was found in the crystalline form of raffinose. From the analysis of the TSDC data, we conclude that these molecular motions are local and noncooperative. A sub-T_g relaxation, or secondary process, was also detected and analyzed by TSDC in the amorphous phase. It has low activation energy and low degree of cooperativity. The glass transition was studied by DSC. The fragility index (Angell’s scale) of raffinose obtained from DSC data is m = 148.Conclusions TSDC proved to be an adequate technique to study the molecular mobility in the crystalline pentahydrate form of raffinose. In the amorphous form, on the other hand, the secondary relaxation was analyzed by TSDC, but the study of the glass transition relaxation was not possible by this experimental technique as a consequence of conductivity problems. The DSC study of the glass transition indicates that raffinose is an extremely fragile glass former.     

Molecular Mobility and Fragility in Indomethacin: A Thermally Stimulated Depolarization Current Study

Purpose. To show that thermally stimulated depolarization currents (TSDC), which is a dielectric experimental technique relatively unknown in the pharmaceutical scientists community, is a powerful technique to study molecular mobility in pharmaceutical solids, below their glass transition temperature (T_g). Indomethacin (T_g = 42°C) is used as a model compound. Methods. TSDC is used to isolate the individual modes of motion present in indomethacin, in the temperature range between –165°C and +60°C. From the experimental output of the TSDC experiments, the kinetic parameters associated with the different relaxational modes of motion were obtained, which allowed a detailed characterization of the distribution of relaxation times of the complex relaxations observed in indomethacin. Results. Two different relaxational processes were detected and characterized: the glass transition relaxation, or -process, and a sub-T_g relaxation, or secondary process. The lower temperature secondary process presents a very low intensity, a very low activation energy, and a very low degree of cooperativity. The fragility index (Angell's scale) of indomethacin obtained from TSDC data is m = 64, which can be compared with other values reported in the literature and obtained from other experimental techniques. Conclusions. TSDC data indicate that indomethacin is a relatively strong glass former (fragility similar to glycerol but lower than sorbitol, trehalose, and sucrose). The high-resolution power of the TSDC technique is illustrated by the fact that it detected and characterized the secondary relaxation in indomethacin, which was not possible by other techniques.     

Evaluation of glassy-state dynamics from the width of the glass transition: results from theoretical simulation of differential scanning calorimetry and comparisons with experiment

The purpose of this study is to investigate the quantitative relationship between the width of the glass transition, DeltaTg, and glass fragility or activation energy for structural relaxation. The ultimate objective is the estimation of structural relaxation time as a function of temperature from the width of the glass transition region, allowing characterization of glass dynamics by a single simple measurement. The Moynihan correlation indicates that activation energy for structural relaxation should be inversely proportional to the width of the glass transition, but recent experimental studies suggest this relationship is a poor approximation for glasses of pharmaceutical interest. The present study is an effort to better understand the validity of the Moynihan correlation by selected experimental studies and a theoretical analysis of those factors that impact the glass transition width. Experimental data for glass transition widths for (poly)vinylpyrrolidone, sucrose, and trehalose are obtained using a variety of procedures, and relaxation time data are obtained using the thermal activity monitor. The theoretical analysis begins by simulating the temperature dependence of the heat capacity by breaking the cooling and heating scans into a large number of temperature steps followed by isothermal holds, during which relaxation of the material is calculated. Here, the modified VTF equation is used for relaxation time and the generalized Kohlraush-Williams-Watts stretched exponential function is used to describe the relaxation kinetics. Simulations are performed for materials of varying fragility and varying "stretched exponential" constants, beta, and the width of the glass transition region, DeltaTg, is evaluated from the simulated heat capacity versus temperature curves as one would do with experimental data. Agreement between the theoretical simulations and experimental DeltaTg data is excellent. The simulations demonstrate that although the Moynihan correlation is not valid for variable beta, a modification of the Moynihan correlation which includes variation in beta is a good approximation. Thus, an estimate of fragility may be obtained from glass transition width data provided an estimate of beta is available. Furthermore, it is shown that a first approximation for beta may be obtained from the magnitude (i.e., height) of the differential scanning calorimetry thermal overshoot. We also find that using the modified VTF equation to evaluate the temperature dependence of the structural relaxation time at the glass transition, and integrating this expression to lower temperatures, it is possible to obtain an evaluation of the relaxation time constant, tau(beta), in the glass at any temperature, using only the DeltaTg and beta values obtained from a single differential scanning calorimetry scan. These estimated time constants correlate very well with the values directly measured with the thermal activity monitor.     

Effect of thermal history on the glassy state of indapamide

The effects of thermal history, e.g. cooling rate, annealing, etc., on the thermal behaviour of indapamide glass were determined by differential scanning calorimetry (DSC). The glass was prepared by heating indapamide crystals (m.p. 162 degrees C) to 180 degrees C, and then cooling the melt to room temperature. The glass transition temperature (Tg) of the material was 98 degrees C. An endotherm, due to thermal relaxation of the glass, was observed in the DSC thermogram when indapamide glass was prepared by slow cooling or was annealed isothermally at a temperature below Tg. Such enthalpy relaxation may be observed during ageing of pharmaceutical glasses and might influence their physico-chemical properties.     

Influence of Cooling Rate on Ice Crystallization and Melting in Sucrose-Water System

The ice crystallization and melting in systems where the equilibrium state is difficult to reach is one of the growing areas in pharmaceutical freeze-drying research. The quality of the final freeze-dried product depends on the parameters of the cooling step, which affect the ice nucleation and growth. In this paper, we present a DSC study of ice crystallization and melting in a sucrose-water system. Using two different types of thermal cycles, we examine the influence of cooling and heating rates on the thermal behavior of sucrose-water solutions with water contents between 50 and 100 wt%.The DSC results show that low cooling rates provide crystallization at higher temperatures and lead to lower amount of non-freezing water. Consequently, the glass transition and ice melting properties observed upon heating depend on the cooling conditions in the preceding step. Based on the experimental results, we investigate the reasons for the existence of the two steps on DSC heating curves in sucrose-water systems: the glass transition step and the onset of ice melting. We show that diffusion of water can be the limiting factor for ice growth and melting in the sucrose-water system when the amorphous phase is in a liquid state. In particular, when the diffusion coefficient drops below 10^?14 m²/sec, the ice crystals growth or melting becomes strongly suppressed even above the glass transition temperature. Understanding the diffusion limitations in the sucrose-water system can be used for the optimization of the freeze-drying protocols for proteins and probiotics.     

Characterization of glassy itraconazole: a comparative study of its molecular mobility below T(g) with that of structural analogues using MTDSC

The objective of the present study was to estimate the molecular mobility of glassy itraconazole below the glass transition, in comparison with structural analogues (i.e. miconazole and ketoconazole).Glassy itraconazole and miconazole were prepared by cooling from the melt. The glassy state of the drug was investigated with modulated temperature DSC using the following conditions: amplitude +/-0.212 K, period 40 s, underlying heating rate 2 K/min. The glass transition was determined from the reversing heat flow and occurred at 332.4 (+/-0.5) K and 274.8 (+/-0.4) K for itraconazole and miconazole, respectively. The jump in heat capacity at the glass transition was 303.42 (+/-3.43) J/mol K for itraconazole and 179.35 (+/-0.89) J/mol K for miconazole. The influence of the experimental conditions on the position of the glass transition of itraconazole was investigated by varying the amplitude from +/-0.133 to +/-0.292 K and the period from 25 to 55 s, while the underlying heating rate was kept constant at 2 K/min. Glass transition temperature, T(g), was not significantly influenced by the frequency of the modulation nor by the cooling rate. However, the relaxation enthalpy at the glass transition increased with decreasing cooling rate indicating relaxation during the glass formation process. To estimate the molecular mobility of the glassy materials, annealing experiments were performed from T(g)--10 to T(g)--40 K for periods ranging from 15 min to 16 h.Fitting the extent of relaxation of glassy itraconazole to the Williams--Watts decay function and comparing the obtained values with those of amorphous miconazole and ketoconazole indicated that the molecular mobility is influenced by the complexity of the molecular structure. The more complex the structure, the more stable the amorphous state.     

A Comparison of the Physical Stability of Amorphous Felodipine and Nifedipine Systems

Purpose The objective of this study was to investigate thermodynamic and kinetic factors contributing to differences in the isothermal nucleation rates of two structurally related calcium channel blockers, nifedipine and felodipine, both alone and in the presence of poly(vinylpyrrolidone) (PVP).Materials and Methods Thin films of amorphous systems were cast onto glass slides and the nucleation rate was determined using optical microscopy. Enthalpy, entropy, and free energy of crystallization of the pure compounds were measured using differential scanning calorimetery (DSC). Molecular mobility and glass transition temperature of each amorphous system were characterized using DSC and hydrogen bonding patterns were analyzed with infrared spectroscopy. The composition dependence of the thermodynamic activity of the amorphous drug in the presence of the polymer was estimated using Flory‐Huggins lattice theory.Results Nifedipine crystallized more readily than felodipine from the metastable amorphous form both alone and in the presence of PVP despite having a similar glass transition temperature and molecular mobility. Nifedipine was found to have a larger enthalpic driving force for crystallization and a lower activation energy for nucleation.Conclusions The properties of the metastable form alone did not explain the greater propensity for nifedipine crystallization. When considering the physical stability of amorphous systems, it is important to also consider the properties of the crystalline counterpart.     

The Molecular Mobility of Supercooled Amorphous Indomethacin as a Function of Temperature and Relative Humidity

Purpose. To determine the relaxation times of supercooled indomethacin as a function of temperature and relative humidity above Tg, and to analyze the results in the context of being able to predict such behavior at various storage conditions. Methods. Dielectric relaxation times were measured in the frequency domain (12 to 10⁵ Hz) for amorphous indomethacin equilibrated at 0, 56, and 83% relative humidity. The heating rate dependence of Tg for dry supercooled indomethacin was measured with differential scanning calorimetry and used to determine relaxation times. The results were compared with previously published shear relaxation times and enthalpy recovery data. Results. Very good agreement was observed between dielectric and shear relaxation times, and those obtained from the heating rate dependence of the Tg, for dry indomethacin as a function of temperature above Tg. The introduction of water lowered the dielectric relaxation times of supercooled indomethacin without significantly affecting its fragility. The relaxation times below Tg, found to be lower than those predicted by extrapolation of the data obtained above Tg, were analyzed in the context of the Adam-Gibbs-Vogel equation. Conclusions. The relaxation times of amorphous indomethacin obtained from the heating rate dependence of Tg were in good agreement with those obtained from shear and dielectric measurements, thus validating a relatively simple approach of assessing molecular mobility. The significant molecular mobility of amorphous indomethacin observed below Tg, and the significant plasticizing effects of sorbed water, help to explain why amorphous indomethacin crystallizes well below Tg over relatively short time scales.     

Crystallisation of amorphous mannitol is retarded using boric acid

An approach to inhibit the crystallisation of amorphous mannitol was investigated. Boric acid was selected as a model additive for a fundamental study of its ability to retard crystallisation and to facilitate characterisation of the properties of the amorphous solid. At concentrations above 5% (w/w) of boric acid, the DSC scans indicated that a totally amorphous solid could be prepared by cooling the melted pre-mixture under ambient conditions. An increase in the glass transition temperature (T(g)) was observed with a corresponding increase in boric acid content, and their relationship was well fitted by the Gordon-Taylor equation. This result suggested that mannitol and boric acid mixed homogeneously.The crystallisation profiles of the resultant amorphous compositions were best described by the Avrami-Eroféev equation (n=1/3), which indicated that random nucleation and three-dimensional crystal growth was the best-fitting mechanism of this crystallisation. The activation energy of crystallisation decreased with increasing boric acid content, indicating that the temperature dependency for crystallisation decreased with increasing boric acid content. Furthermore, the rate of crystallisation at 30 degrees C for mannitol alone was 7000 times higher than that of mannitol containing 7.5% (w/w) of boric acid.     

Characterization of amorphous solids with weak glass transitions using high ramp rate differential scanning calorimetry

Measurement of the glass transition temperature (T(g)) of proteins and other high molecular weight polymers in the amorphous state is often difficult, since the transition is extremely weak, that is, the DeltaC(p) at the glass transition temperature is small. For example, little is known about the solid-state properties of hydroxyethyl starch (HES), which is beginning to become more commonly evaluated as a bulking agent in pharmaceutical products. For weak thermal events, such as the change in heat capacity at the T(g) of a pure protein or large synthetic polymer, increased heating rate should produce greater sensitivity in terms of heat flow. Recent innovations in rapid scanning technology for differential scanning calorimetry (DSC) allow measurements on materials where the thermal events are difficult to detect by conventional DSC. In the current study, measurements of the T(g) of proteins in the solid state, amorphous pharmaceutical excipients which have small DeltaC(p) at the glass transition temperature, and bacterial spores, have all been made using high ramp rate DSC, providing information on materials that was inaccessible using conventional DSC methods.     

The use of amorphous model substances to study mechanically activated materials in the solid state

Spray drying of aqueous solutions of sucrose and lactose produced amorphous solids that differed greatly from their crystalline counterparts in morphology, X-ray diffraction patterns, DSC scans and their water vapour uptake behaviour. Amorphous sucrose and lactose, being in high energy states, are thermodynamically and physically unstable. When exposed to high humidity, they took up moisture to a certain critical uptake level, depending on temperature, then crystallised and released the sorbed moisture. The crystallisation was described as a deactivation process as it ordered the constituent molecules as well as reduced the total energy content of the system. Water vapour uptake of amorphous sucrose and lactose reduced the glass transition temperature (Tg). The Tg was also affected by the heating rate during the DSC scan. When Tg was reduced to, or below, the operating temperature, transformation of the amorphous solids from the glassy state to the rubbery state occurred. The transformation set up conditions for crystallisation to occur. The time delay for crystallisation depended on the temperature difference between the operating temperature and Tg.     

Physical stability and solubility advantage from amorphous celecoxib: the role of thermodynamic quantities and molecular mobility

Glassy pharmaceuticals, characterized by excess thermodynamic properties, are theoretically more soluble than their crystalline counterparts. The practical solubility advantage of the amorphous form of celecoxib (CEL) is lost due to its proclivity to lose energy and undergo solvent-mediated devitrification. Theoretical assessment of solubility advantage using differences in isobaric heat capacities (Cp) revealed a 7-21-fold enhancement in the solubility of the amorphous form over that of the crystalline state of CEL. The present study attempts to unveil these differences between experimental and theoretical solubility using thermodynamic parameters such as free energy, enthalpy, and entropy. Amorphous CEL exhibited 1.3-1.5 times enhancement in Cp over that for the crystalline form. The zero and critical molecular mobility regions, represented by Kauzmann temperature (TK) and glass transition temperature (Tg), were found to lie near 246 and 323 K, respectively, for amorphous CEL. The fictive temperature (Tf), an indicator of the configurational entropy of glass, was determined for glassy CEL, signifying the retention of considerable molecular mobility in the glassy phase that may favor nucleation even below Tg. Further, the estimation of various thermodynamic quantities and strength/fragility parameters (D = 11.5 and m = 67.0) postulated the classification of glassy CEL into moderately fragile liquid, as per Angell's classification. A comprehensive understanding of such thermodynamic facets of amorphous form would help in rationalizing the approaches toward development of stable glassy pharmaceuticals with adequate solubility advantage.     

Effect of Compression on Non-isothermal Crystallization Behaviour of Amorphous Indomethacin

Purpose

To evaluate the effect of tablet compression on the physical stability of amorphous indomethacin.

Methods

The amorphous indomethacin generated by melt cooling, rapid (5°C/min) or slow (0.2°C/min) cooling, was evaluated by PXRD, mDSC and FTIR analysis. Non-isothermal crystallisation behaviour was assessed using mDSC and any structural changes with compression were monitored by FTIR. Amorphous indomethacin was compressed in a DSC pan using a custom made die cavity-punch setup and further analysed in the primary container to minimize stress due to sample transfer and preparation.

Results

Compression of amorphous indomethacin induced and increased the extent of crystallisation upon heating. DSC results revealed that amorphous indomethacin generated by rapid cooling is more prone to compression induced crystallisation than the slowly cooled one. Onset temperature for crystallisation (T _c ) of uncompressed slowly and rapidly cooled samples are 121.4 and 124°C and after compression T _c decreased to ca 109 and ca 113°C, respectively. Compression of non-aged samples led to higher extent of crystallisation predominantly into ??-form. Aging followed by compression led to crystallisation of mainly the ??-form.

Conclusions

Compression affects the physical stability of amorphous indomethacin. Structural changes originated from tablet compression should be duly investigated for the stable amorphous formulation development.     

Detection of Low Levels of the Amorphous Phase in Crystalline Pharmaceutical Materials by Thermally Stimulated Current Spectrometry

Purpose. 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 (T_g) 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 T_g 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.     

Effect of counterions on the properties of amorphous atorvastatin salts

Amorphous systems have gained importance as a tool for addressing delivery challenges of poorly water soluble drugs. A careful assessment of thermodynamic and kinetic behavior of amorphous form is necessary for successful use of amorphous form in drug delivery. The present study was undertaken to evaluate effect of monovalent sodium (Na(+); ATV Na), and bivalent calcium (Ca(2+); ATV Ca) and magnesium (Mg(2+); ATV Mg) counterions on properties of amorphous salts of atorvastatin (ATV) model drug. Amorphous form was generated from crystalline salts of ATV by spray drying, and characterized for glass transition temperature (T(g)), fragility and devitrification tendency. In addition, chemical stability of the amorphous salt forms was evaluated. Fragility was studied by calculating activation enthalpy for structural relaxation at T(g), from heating rate dependency of T(g). Density functional theory and relative pK(a)'s of counterions were evaluated to substantiate trend in glass transition temperature. T(g) of salts followed order: ATV Ca>ATV Mg>ATV Na. All salts were fragile to moderately fragile, with D value ranging between 9 and 16. Ease of devitrification followed the order: ATV Na～ATV Mg?ATV Ca, using isothermal crystallization and reduced crystallization temperature method. Chemical stability at 80°C showed higher degradation of amorphous ATV Ca (～5%), while ATV Na and ATV Mg showed degradation of 1-2%. Overall, ATV Ca was better in terms of glass forming ability, higher T(g) and physical stability. The study has importance in selection of a suitable amorphous form, during early drug development phase.     

Solid-State Characteristics of Amorphous Sodium Indomethacin Relative to Its Free Acid

Purpose. Having previously studied the amorphous properties of indomethacin (IN) as a model compound for drugs rendered amorphous during processing, we report on the formation and characterization of its sodium salt in the amorphous state and a comparison between the two systems. Methods. Sodium indomethacin (SI) was subjected to lyophilization from aqueous solution, rapid precipitation from methanol solution, and dehydration followed by grinding to produce, in each case, a completely amorphous form. The amorphous form of SI was analyzed using DSC, XRD, thermomicroscopy and FTIR. The method of scanning rate dependence of the glass transition temperature, Tg, was used to estimate the fragility of the SI system. Enthalpy relaxation experiments were carried out to probe the molecular mobility of the SI system below Tg. Results. The amorphous form of SI formed by different methods had a Tg equal to 121°C at a scanning rate of 20°C/min. This compares with a Tgfor indomethacin of 45°C. Estimation of fragility by the scanning rate dependence of Tg indicates no significant differences in fragility between ionized and unionized forms. Enthalpy relaxation measurements reveal very similar relaxation patterns between the two systems at the same degree of supercooling relative to their respective Tg values. Conclusions. The amorphous form of SI made by various methods has a Tg that is about 75°C greater than that of IN, most likely because of the greater density and hence lower free volume of SI. Yet, the change of molecular mobility as a function of temperature relative to Tgis not very different between the ionized and unionized systems.