Physico-chemical characterization and stability study of glassy simvastatin

The objective of the present study was to investigate the glass forming capability of a model drug simvastatin. The glassy material produced by melt quench technique was subjected to physico-chemical characterization and subsequent stability and enthalpy relaxation study. The chemical stability of drug during preparation of glass was tested by High Performance Liquid Chromatography (HPLC) and Infrared (IR) spectroscopy. The presence of amorphous form was confirmed by DSC and XRPD. Surprisingly, glassy simvastatin was almost stable throughout the period of stability, inspite of its T_g being relatively low. The stability and very low enthalpy recovery of glassy simvastatin perhaps could be attributed to strong inter-molecular hydrogen bonding.     

A crystallization study of the Ge25Sb20S55 glassy alloy

Differential scanning calorimetry analysis was used to gain insight on the thermal stability and calorimetric behaviour on heating of the Ge₂₅Sb₂₀S₅₅ glassy alloy. The as-quenched glass shows a glass transition atT _g=570 K. From the variation ofT _g with the heating rate a value of h=240 kJ mol^–1 was obtained for the activation enthalpy of the mean relaxation time. On further heating an exothermic process appears ranging from 725 to 800 K giving rise to glassy GeS₂ and needle-like crystals of antimony. The microstructure of the crystallization product was obtained from X-ray diffraction and scanning electron microscopy. The resulting material shows two glass transitions. The crystallization process is explained correctly by the Johnson-Mehl-Avrami-Erofe'ev equation with a kinetic exponent ofn=1.6. The apparent activation energy of crystallization is evaluated asE=286 kJ mol^–1.     

Viscous flow behaviour of NixZr100−x metallic glasses from Ni30Zr70 to Ni64Zr36

The compositional dependence of viscous flow in the Ni _x Zr_100–x amorphous system was investigated under non-isothermal conditions at a heating rate of 10 K min^–1in the compositional range fromx=30 tox=64 at % with the aid of a Hereaus TMA 500 dilatometer. The crystallization behaviour of the same glassy alloys under the same non-isothermal conditions was studied with a Perkin-Elmer DSC 7 differential scanning calorimeter. The characteristic crystallization and viscous flow parameters (the onset temperature,T _x, of crystallization; the temperature,T _m, of maximum heat evolution of the first crystallization step; the enthalpy, H _x, of crystallization; the activation energy,Q _x, of crystallization; the glass transition temperature,T _g; the viscosity values (T _g) and _min; and the activation energy for viscous flowQ (T>T _g), were shown to be dependent on composition. This dependence was examined on the basis of the equilibrium phase diagram of the Ni-Zr-system, and it is shown that glassy alloys possessing eutectic compositions manifest the greatest thermal stability because of the long-range atomic diffusion needed for crystallization to occur. Glassy alloys with nearly peritectoid compositions show low thermal stability, as no long-range diffusion is needed for the formation of the stable crystallization end-products NiZr₂ and NiZr. In all cases, the crystallization process is governed by viscosity flow of these glassy alloys.     

Glass forming ability and thermal stability of some Se–Sb glassy alloys

Alloys of Se–Sb glass system, obtained with rapid quenching, have been thermally characterized with calorimetric measurements. The Hruby number (H_R), which is the strong indicator of glass forming tendency (GFT), thermal stability parameter (S) representing resistance to divitrification, the values of crystallization enthalpy (ΔH_c) and entropy changes during amorphous to crystalline phase transition (i.e., during crystallization process) have been evaluated for these glassy alloys. The compositional dependence of various kinetic and thermodynamic parameters has been discussed. The fragility index (F) for the present glasses has been determined to see whether these materials are obtained from kinetically strong-glass-forming (KS) or kinetically fragile-glass-forming (KF) liquids.     

Energy and entropy of crystals,melts and glasses or what is wrong in Kauzmann's paradox?

In order to understand the thermodynamic properties of solids and melts one has to consider simultaneously their entropy and energy as a function of temperature. Therefore, the molar entropy, S, and enthalpy (energy), H, of crystals, glasses and melts of the same one‐component systems have been suitably depicted including the transformation from the melt into a solid, i. e. a glass or crystal. S and H of glasses correspond to a simple continuation of these functions from the molten state to lower temperatures. Since crystallisation occurs spontaneously such a process necessarily produces entropy causing the temperature to increase. Thus, the glassy and the crystalline state are not connected by an isothermal process, which is in contrast to the assumption in the classical nucleation and crystallisation theory as well as in the arguments causing Kauzmann's paradox. For the temperature T → 0K the enthalpy and entropy of the glass are larger by ΔH₀ and ΔS₀ as compared to the stable crystal. The calculations are illustrated using experimental data for quartz and silica glass from P. Richet, Y. Bottinga, L. Deniélou, J. P. Petitet and C. Téqui.     

Structural transition in poly(methyl methacrylate) due to large deformation at temperatures below the equilibrium second-order transition temperature

To analyse the structural change in glassy polymers under large deformation at low temperatures, poly(methyl methacrylate) specimens were uniaxially compressed at temperatures below the equilibrium second-order transition temperature T ₂ with varying strain rates. The state of steady plastic flow which appeared in the lower yield range of the stress-strain curve was analysed using the Eyring equation in a novel way. This analysis provided the following results: at low temperatures, the volume of a flow unit decreased with temperature, probably approaching the least critical value; and a functional relation between the activation enthalpy H and the activation entropy S for the glass deviated gradually from that for the melt derived from the WLF equation with decreasing temperature. This deviation could be attributed to the structural transition of the glass into liquid-like structures of the melt at elevated temperatures above T _g + 100 K where the WLF equation is no longer available.     

Investigation of crystallisation kinetics of Bi0·5Se99·5-xZnx glasses by differential scanning calorimetry

Abstract

The kinetics of crystallisation in Bi_0·5Se_99·5-xZn_x (x=0, 0·1, 0·2, 0·5, 1·0) glasses are studied by non-isothermal method using differential scanning calorimetry. Differential thermal analysis was performed at different heating rates of 5, 10, 15, and 20 K min^-1. The values of glass transition and crystallisation temperatures are found to be composition and heating rate dependent. From the heating rate dependence of the glass transition and crystallisation temperatures, the activation energy of crystallisation ΔE _c, the order parameter n and the enthalpy released ΔH _c are calculated. The thermal stability (T _c–T _g) was found to be maximum for Bi_0·5Se_99·5 glass, which suggest that this glass can be considered as a critical composition at which the system becomes chemically ordered. The crystallisation enthalpy ΔH _c is maximum for Bi_0·5Se₉₉Zn_0·5 glass, hence it is the least stable glass in the present system.     

Non-isothermal kinetic studies for binary TeO2-P2O5 glass system

A study of TeO₂–P₂O₅ glass system has been carried out by Differential Thermal Analysis (DTA) to elucidate the kinetics of crystallization for these glassy samples. The results of DTA performed at different heating rates are discussed. The values of the glass transition temperature, T _g , as well as the glass crystallization temperature, T _c , are found to be dependent upon the heating rate. From this dependence, the values of activation energy for both the glass transition and crystallization are evaluated and discussed     

Enthalpy relaxation studies of two structurally related amorphous drugs and their binary dispersions

Objective: The purpose of the current study was to evaluate the enthalpy relaxation behavior of valdecoxib (VLB) and etoricoxib (ETB) and their binary dispersions to derive relaxation constants and to understand their molecular mobilities. Methods: Solid dispersions of VLB and ETB were prepared with 1%, 2%, 5%, 10%, 15%, and 20% (w/w) concentrations of polyvinylpyrrolidone (PVP) in situ using differential scanning calorimetry (DSC). Enthalpy relaxation studies were carried out with isothermal storage periods of 1, 2, 4, 6, 16, and 24 hours at 40°C and 0% relative humidity (RH). Results: PVP increased the glass transition temperature (T_g) and decreased the enthalpy relaxation. Significant differences between two drugs were observed with respect to their relaxation behavior which may be due to differences in intermolecular interactions as predicted by Couchman–Karasz equation and molecular mobility. Kohlrausch–Williams–Watts equation was found to be inadequate in describing complex molecular relaxations in binary dispersions. The enthalpy relaxation behavior of VLB and ETB was found to be significantly different. PVP stabilized VLB significantly; however, its effect on ETB was negligible. The extent of enthalpy relaxation was found to correlate with hydrogen bonding tendency of the drug molecules. Conclusion: The outcome can help in rational designing of amorphous systems with optimal performance.     

Gd–Ni–Al bulk glasses with great glass-forming ability and better mechanical properties

A series of Gd–Ni–Al ternary glassy alloys with the maximum diameter of 4 mm were obtained by common copper mold casting. The maximum values of the reduce glass transformation temperature (T _g/T _m) and the distance of supercooling region ΔT _x of these alloys in this study were 0.648 and 50 K, respectively. The compressive fracture strength (σ _f) and Young’s modulus (E) of Gd–Ni–Al glassy alloys were 1,240–1,330 MPa and 63–67 GPa, respectively. The magnetic properties of these BMGs were investigated. The Gd–Ni–Al bulk glassy alloys with great glass forming ability and good mechanical properties are promising for the future development as a new type of function materials.     

Controlled release of drugs from cellulose acetate matrices produced from sugarcane bagasse: monitoring by square-wave voltammetry

In this paper, cellulose triacetate (CTA) was produced from sugarcane bagasse and used as matrices for controlled release of paracetamol. Symmetric and asymmetric membranes were obtained by formulations of CTA/dichloromethane/drug and CTA/dichloromethane/water/drug, respectively, and they were characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). Different morphologies of membranes were observed by SEM, and the incorporation of paracetamol was confirmed by lowering of the glass transition temperature (T_g) in the DSC curves. This indicates the existence of interactions between the matrix and the drug. The evaluation of drug release was based on the electrochemical monitoring of paracetamol through its oxidation at a glassy carbon electrode surface using square-wave voltammetry (SWV), which provides fast, precise and accurate in situ measurements. The studies showed a content release of 27% and 45% by the symmetric and asymmetric membranes, respectively, during 8?h.     

Effect of Nb addition on the subsurface deformation behavior in Cu47Ti34Zr11Ni8 bulk metallic glasses through Vickers indentation

In this paper, 3 mm diameter (Cu₄₇Ti₃₄Zr₁₁Ni₈)_100−xNb_x (x = 0,1,2) glass forming alloys were fabricated by water-cooled copper mould cast. Microstructural characterization reveals that the monolithic Cu₄₇Ti₃₄Zr₁₁Ni₈ bulk metallic glass exhibits homogenous amorphous structure. While the alloys with Nb addition exhibit a composite structure. For alloys with x = 1, micro-scaled crystalline particles were found to distribute in the glassy matrix. For alloys with x = 2, the microstructure is dominated by a high density of dendritic phase embedded in the glassy matrix. Bonded interface technique was adopted to study the deformation behavior of the alloys underneath the Vickers indentation. It reveals that the subsurface shear patterns are significantly affected by the precipitated phases. The different deformation mechanism of the alloys resulted from the minor Nb addition was put forward and discussed.     

DSC study of some Ge-Sb-S glasses

Differential scanning calorimetric analysis was made on three glasses of the Ge-Sb-S system in order to obtain insight into the kinetics of glass transition and of the inherent relaxation processes occurring in the glass transition region. The heat capacity of the supercooled liquid referred to as the glass was measured. The value of the heat capacity jump at the glass transition, C_p, has been obtained for each glass. These values are in good agreement with those found for similar chalcogenide glasses. The relaxation process in the glassy alloy Ge₃₀Sb₁₀S₆₀ was investigated by measuring the excess heat capacity of the annealed glass in the glass transition region. A relaxation enthalpy of 2.7 meV for annealing at 595 K for 17 h was determined. A kinetic study of the glass transition in the Ge₂₀Sb₁₀S₇₀ glass was done. From the change in the glass transition temperature with scanning rate, an apparent activation energy of 3.9 eV was obtained. This value agrees with those measured for the apparent activation energy of the shear viscosity in similar glasses.     

Thermal rejuvenation in metallic glasses

Abstract

Structural rejuvenation in metallic glasses by a thermal process (i.e. through recovery annealing) was investigated experimentally and theoretically for various alloy compositions. An increase in the potential energy, a decrease in the density, and a change in the local structure as well as mechanical softening were observed after thermal rejuvenation. Two parameters, one related to the annealing temperature, T_a/T_g, and the other related to the cooling rate during the recovery annealing process, V_c/V_i, were proposed to evaluate the rejuvenation phenomena. A rejuvenation map was constructed using these two parameters. Since the thermal history of metallic glasses is reset above 1.2T_g, accompanied by a change in the local structure, it is essential that the condition of T_a/T_g ≥ 1.2 is satisfied during annealing. The glassy structure transforms into a more disordered state with the decomposition of icosahedral short-range order within this temperature range. Therefore, a new glassy structure (rejuvenation) depending on the subsequent quenching rate is generated. Partial rejuvenation also occurs in a Zr₅₅Al₁₀Ni₅Cu₃₀ bulk metallic glass when annealing is performed at a low temperature (T_a/T_g ~ 1.07) followed by rapid cooling. This behavior probably originates from disordering in the weakly bonded (loosely packed) region. This study provides a novel approach to improving the mechanical properties of metallic glasses by controlling their glassy structure.     

Thermal characterization of glassy Se70Te20M10 using DSC technique

Differential scanning calorimetry (DSC) has been employed to study the phase transformation in glassy Se₇₀Te₂₀M₁₀ (M = Ag, Cd, Sb) to understand the glass forming tendency (GFT) and rate of crystallization. The difference (T _c–T _g) (indicator of GFT and thermal stability) has been determined by DSC thermograms for each sample. The values of T _c and T _g are found to depend on GFT. The rate constant K (indicator of rate of amorphous to crystalline phase transformation) has been evaluated using method of Augis and Bennett. The parameter K is also found to be related with (T _c–T _g).     

Influence of post-curing and temperature effects on bulk density,glass transition and stress-strain behaviour of imidazole-cured epoxy network

The effects of post-curing and temperature on the glass transition, bulk density and stress-strain behaviour in the glassy and rubbery state of 2-ethyl-4-methyl imidazole-cured epoxy network have been evaluated by differential scanning calorimetry (DSC), water displacement and tensile testing. The glass transition temperature,T _g, was found to increase with increasing post-cure temperature and the size of the base line shift in the glass transition region on the DSC thermogram can serve as an indicator of the extent of cure. At room temperature, the decrease in bulk density with increasing extent of cure may be attributed to the additional cross-linking, adding molecular constraints to the thermal constraints. Thus, a higher free volume atT _g can be expected to remain in the glassy state as the sample is slowly cooled through the glass transition temperature. In the investigation on the temperature dependence of the tensile mechanical properties, a fracture envelope was obtained. The tensile strength, Young's modulus and ultimate elongation in the glassy and rubbery state are discussed in detail.     

Glass-forming ability and thermoplastic formability of a Pd<Subscript>40</Subscript>Ni<Subscript>40</Subscript>Si<Subscript>4</Subscript>P<Subscript>16</Subscript> glassy alloy

The glass-forming ability of a Pd₄₀Ni₄₀Si₄P₁₆ alloy has been investigated. This alloy exhibits a wide supercooled liquid region of 107 K, a high reduced glass transition temperature of 0.596 and a small fragility parameter of 28, indicating that this alloy is a good glass former. Using flux treatment, the Pd₄₀Ni₄₀Si₄P₁₆ alloys can be easily produced as centimeter-scale metallic glasses. The glass transition and crystallization kinetics of this alloy were investigated by means of both differential scanning calorimetry (DSC) and differential isothermal calorimetry (DIC). Thermoplastic forming of the Pd₄₀Ni₄₀Si₄P₁₆ glassy alloy is easily performed due to the high thermal stability and low viscosity of the supercooled liquid. By pressing a “flat” silicon wafer onto a sample within the thermoplastic forming region, the surface of the Pd₄₀Ni₄₀Si₄P₁₆ metallic glasses could be significantly smoothened. The final surface showed a reduced root mean square roughness R _q as low as ~2 nm. This indicates a simple approach to prepare “flat” surfaces for metallic glasses.     

Solubility advantage from amorphous etoricoxib solid dispersions

Objective: This study aimed to evaluate kinetic solubility advantage of amorphous etoricoxib solid dispersions prepared with three water soluble polymers and correlate it with solid state and supersaturated drug solution stabilization potential of these polymers.

Methods: Amorphous solid dispersions (ASDs) of etoricoxib were prepared with polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP) and hydroxyethyl cellulose (HEC) at 70:30w/w ratio and characterized for glass transition temperature (T_g), miscibility and intermolecular interactions. Kinetic solubility profiles of amorphous etoricoxib and its ASDs were determined in water at 37 °C. Solid-state stability was assessed by enthalpy relaxation studies at a common degree of undercooling of around 19.0 °C at 0% RH. Recrystallization behavior of supersaturated drug solution was evaluated in the absence and presence of pre-dissolved polymer at 37 °C.

Results: Amorphous etoricoxib exhibited rapid solid-to-solid transition to yield a solubility advantage of merely 1.5-fold in water. Among the ASDs, etoricoxib-PVP dispersion exhibited maximal “peak” (2-fold) and “plateau” (1.8-fold) solubility enhancement, while etoricoxib-PVA dispersion could only sustain the “peak” solubility achieved by amorphous etoricoxib. In contrast, etoricoxib-HEC dispersion displayed no solubility advantage. The rank order for solid state and supersaturated solution stabilization followed a similar trend of amorphous etoricoxib?Conclusion: Dissolution behavior of ASDs is influenced by concomitantly occurring solid phase changes, thus understanding these processes independently can enable assessment of the predominant route of drug crystallization and stabilization by the polymer.     

The Potential of Small-Scale Fusion Experiments and the Gordon-Taylor Equation to Predict the Suitability of Drug/Polymer Blends for Melt Extrusion

The aim of this study was to investigate the use of small-scale fusion experiments and the Gordon-Taylor (GT) equation to predict whether melt extrusion of a drug with an amorphous polymer produces a stable amorphous dispersion with increased drug dissolution. Indomethacin, lacidipine, nifedipine, piroxicam, and tolbutamide were used as poorly soluble drugs. Drug/polyvinylpyrrolidone (PVP) blends were prepared at a 1:1 mass ratio. Small-scale fusion experiments were performed in a differential scanning calorimeter (DSC) and in stainless steel beakers. Extrusion was performed in a Brabender Plasti-corder. The glass transition temperatures T_g were determined by DSC. Taking an average T_g from the DSC melt, beaker melt, and GT equation accurately predicted the extrudate T_g. Physical stability of beaker melt and extrudate samples was tested by X-ray powder diffraction (XRPD) and DSC after storage at 30°C (beaker melt) or 25°C (extrudate) and less than 10%, 60%, and 75% relative humidity (RH). Beaker melts were amorphous, apart from some residual crystallinity. Extrudates were amorphous after preparation. Except for indomethacin/PVP, which remained amorphous, the crystallinity of beaker melts and extrudates increased only at 75% RH. Recrystallization occurred even when the T_g of the sample was well above the storage temperature. Chemical stability of the beaker melts and extrudates was tested by capillary electrophoresis and high-performance liquid chromatography (HPLC). Stability was slightly improved in the extrudate compared to the beaker melt. In general, the order for rate of dissolution was crystalline drug was less than the physical mixture, which was less than the drug/PVP beaker melt, which was approximately equal to the extrudate. The use of beaker melts allows a conservative estimate of the potential to melt extrude a drug. To predict physical stability, analysis of the T_g must be combined with physical stability experiments.     

Kinematical studies of the glass transition in glassy Se80 ? xTe20Sbx

The present paper reports kinematic studies of the glass transition in glassy Se_80-xTe₂₀Sb_x alloys using the differential scanning calorimetric technique. The glass transition temperature (T_g) is found to increase monotonically with the heating rate. T_g also increases with the increase of Sb concentration in ternary Se_80-xTe₂₀Sb_x system. From the heating rate dependence of glass transition temperature, the activation energy ( E_t) for the relaxation time controlling the structural enthalpy, is calculated. The composition dependence of T_g and E_t is discussed in terms of the structure of the Se-Te-Sb glassy system.