Reduced Crystallization Temperature Research Articles

An Investigation of the Impact of Precipitation Temperature and Filter Cake Thickness on the Physical Stability of Amorphous Solids: A Case Study.

The purpose of this study was to resolve the issue of physical instability in amorphous solid drugs, which can result in unwanted crystallization, affecting solubility and dissolution rates. The focus was on precipitating physically stable amorphous forms of the nilotinib free base, an anticancer drug, by monitoring preparation conditions such as precipitation temperature and filter cake thickness. A comprehensive set of characterization techniques, including powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and focused beam reflectance measurement (FBRM), were used. These were supplemented by advanced data analysis methods that incorporated pair distribution function (PDF), reduced crystallization temperature (Rc), and principal component analysis (PCA) to evaluate the physical stability of the amorphous samples. Results emphasized that optimal physical stability was achieved when amorphous solids were prepared at a precipitation temperature of 10 °C and a filter cake thickness of 4 cm. Moreover, the integration of PDF analysis with Rc values was confirmed as an innovative approach for assessing physical stability, thus offering enhanced efficiency and accuracy over conventional accelerated stability testing methods.

Investigation of the Influence of Anti-Solvent Precipitation Parameters on the Physical Stability of Amorphous Solids.

Amorphous solids exhibit enhanced solubility and dissolution rates relative to their crystalline counterparts. However, attaining optimal bioavailability presents a challenge, primarily due to the need to maintain the physical stability of amorphous solids. Moreover, the precise manner in which precipitation parameters, including the feeding rate of the anti-solvent, agitation speed, and aging time, influence the physical stability of amorphous solids remains incompletely understood. Consequently, this study aimed to investigate these three parameters during the precipitation process of the anticancer drug, nilotinib free base. The physical stability of the resultant samples was evaluated by employing characterization techniques including powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), focused beam reflectance measurement (FBRM), and data analysis methods such as pair distribution function (PDF), reduced crystallization temperature (Rc), and principal component analysis (PCA). This study's findings indicated that amorphous solids exhibited the greatest physical stability under particular conditions, namely a feeding rate of 5 mL/min, an agitation speed of 500 rpm, and an aging time of 10 min. Furthermore, the physical stability of the amorphous solids was primarily influenced by particle size and distribution, molecular interactions, microstructure, surface area, and interfacial energy. Notably, the parameters involved in the anti-solvent precipitation process, including the feeding rate of the anti-solvent, agitation speed, and aging time, exerted a significant impact on these factors. Consequently, they directly affected the physical stability of amorphous solids. Hence, this study comprehensively elucidated the mechanistic influence of these operational parameters on the physical stability of amorphous solids during the anti-solvent precipitation process.

Optimization of precipitation conditions for producing physically stable amorphous solids using pair distribution function and reduced crystallization temperature

The physically unstable amorphous solid drug can transform into a crystalline state, reducing solubility and dissolution rate. This study aimed to prepare physical stability anticancer drug nilotinib free base amorphous solids by modifying parameters associated with amorphous precipitation, including washing water volume, drying time, and anti-solvent/solvent ratio. Characterization involved powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and data analysis involved pair distribution function (PDF), reduced crystallization temperature (Rc), and principal component analysis (PCA) were applied for the physical stability evaluation. The results revealed that amorphous solids showed the highest physical stability under specific conditions: 50 mL washing water volume, 18 h drying time, and 40 anti-solvent/solvent ratio. Hence, it was demonstrated that the method combining PDF analysis and Rc values provided a novel and comprehensive assessment of physical stability, offering enhanced speed and accuracy compared to traditional accelerated stability test approaches.

In-situ studies of primary nucleation and growth of the cubic Al19Fe4MnSi2 phase in an Al–Fe–Mn–Si metallic glass

The crystallization process of amorphous/glassy alloys below the glass transition temperature when the diffusion processes are hampered is of great interest for study. Here, we measured the growth rate of a crystalline phase with a complex cubic structure in the Al–Fe–Mn–Si metallic glass near the crystallization temperature in-situ by using transmission electron microscopy. We estimated the effective diffusion coefficient that is likely related to the slowest diffusing element (Mn). The results are compared with the crystallization of different other amorphous/glassy alloys considering the reduced crystallization temperature. Notwithstanding of the compositional difference from the matrix growth of the crystalline phase is significantly faster than can be estimated from the corresponding diffusion coefficients found for pure Al and AlFe compound.

Solvent‐Assisted Low‐Temperature Crystallization of SnO2 Electron‐Transfer Layer for High‐Efficiency Planar Perovskite Solar Cells

AbstractA high‐quality polycrystalline SnO2 electron‐transfer layer is synthesized through an in situ, low‐temperature, and unique butanol–water solvent‐assisted process. By choosing a mixture of butanol and water as a solvent, the crystallinity is enhanced and the crystallization temperature is lowered to 130 °C, making the process fully compatible with flexible plastic substrates. The best solar cells fabricated using these layers achieve an efficiency of 20.52% (average 19.02%) which is among the best in the class of planar n–i–p‐type perovskite (MAPbI3) solar cells. The strongly reduced crystallization temperature of the materials allows their use on a flexible substrate, with a resulting device efficiency of 18%.

Reduced Crystallization Temperature Methodology for Polymer Selection in Amorphous Solid Dispersions: Stability Perspective.

API-polymer interactions, used to select the right polymeric matrix with an aim to stabilize an amorphous dispersion, are routinely studied using spectroscopic and/or calorimetric techniques (i.e., melting point depression). An alternate selection tool has been explored to rank order polymers for formation of stable amorphous dispersions as a pragmatic method for polymer selection. Reduced crystallization temperature of API, a parameter introduced by Zhou et al.,1 was utilized in this study for rank ordering interactions in API-polymeric systems. The trends in reduced crystallization temperature monitored over polymer concentration range of up to 20% polymer loading were utilized to calculate "crystallization parameter" or CP for two model systems (nifedipine and BI ABC). The rank order of CP, i.e., a measure of API-polymer interaction, for nifedipine followed the order PVP > PVP-VA > Soluplus > HPMCAS > PV Ac > PAA. This rank ordering was correlated to published results of molecular interactions and physical stability for nifedipine. A different rank ordering was observed for BI ABC: PAA > PVP > HPMCAS > Soluplus > PVPV-VA > PVAc. Interactions for BI ABC were not as differentiated when compared to nifedipine based on CP trends. BI ABC dispersions at drug loadings between 40 and 60% were physically stable for prolonged periods under ICH conditions as well as accelerated stress. We propose that large CP differences among polymers could be predictive of stability outcomes. Acceptable stability at pharmaceutically relevant drug loadings would suggest that the relative influence of downstream processes, such as polymer solubility in various solvents, process suitability and selection, and more importantly supersaturation potential, should be higher compared to stability considerations while developing compounds like BI ABC.

Effects of Open Metal Site Availability on Adsorption Capacity and Olefin/Paraffin Selectivity in the Metal–Organic Framework Cu3(BTC)2

We report a detailed investigation of the factors influencing olefin/paraffin separation in the metal–organic framework (MOF) adsorbent Cu3(BTC)2 (BTC, benzene-1,3,5-tricarboxylate). The effects of synthesis and activation parameters on the availability of open Cu metal sites in the MOF were studied via measurements of crystallinity, textural properties, structural defects, and water desorption, as well as binary 1-hexene/hexane vapor breakthrough chracteristics. A reduced crystallization temperature and improved solvent exchange with methanol were found to lead to CuBTC adsorbents with higher olefin selectivity and capacity. In situ Fourier transform infrared and mass spectrometry measurements were used to quantify the structural defects and availability of open metal sites in the MOF as a function of the activation conditions. Based upon these measurements, we identify the relationships between the defects, activation conditions, open metal site availability, and consequent separation performance. Recom...

Substantially reduced crystallization temperature of SBA-15 mesoporous silica in NaNO3 molten salt

This paper described a simple molten salt method to realize the crystallization of SBA-15 mesoporous silica at a relative low temperature of 500°C under atmospheric pressure. Scanning electron microscopy (SEM), high-magnification transmission electron microscopy (TEM), X-ray diffraction (XRD) and Raman spectrometer were employed to characterize the morphology, crystal structure of prepared products in detail. The SEM results showed that cristobalite nanoparticles of SBA-15 were successfully obtained in NaNO3 molten salt at a relatively low temperature compared with former approaches, which was mainly ascribed to the tiny dosage of sodium ions and the surfactant of P123 in SBA-15 crystallization system.

STUDY ON FORMATION AND CORROSION RESISTANCE OF AMORPHOUS ALLOY IN U-Co SYSTEM

The formation of amorphous phase has been investigated in U-Co system over a wide range of compositions, namely, UxCo100-x (x=50~87.5) by mean of melt-spinning. Phase identification for the arc-melted ingots and rapidly quenched alloys, and the thermal stability of the amorphous phases thus formed have been examined by XRD and DSC, respectively. The component phases in the ingot alloys were structurally the same as those presented in UCo phase diagram, but were associated with a certain compositional metastability. Rapid quenching experiment revealed that the ease of formation of amorphous phase occurred within the composition range of 58.5≤x≤78, and amorphous phase was most readily formed in the vicinity of U66.7Co33.3 composition. The dynamical crystallization temperatures of the amorphous phases were determined to be 534~550 K at a DSC heating rate of 20 K/min, and the highest reduced crystallization temperature (relative to the liquidus temperature) as *国防基础科研计划项目B1520133007和中国工程物理研究院科技发展基金项目2013A0301015资助 收到初稿日期: 2014-10-27,收到修改稿日期: 2015-02-02 作者简介:黄火根,男, 1980年生,副研究员,博士 DOI: 10.11900/0412.1961.2014.00580 第623-630页 pp.623-630

Counter-intuitive effect of non-crystallizing sugars on the crystallization of gemcitabine HCl in frozen solutions

In this study, the effect of four non-crystallizing sugars, namely fructose, trehalose, sucrose and raffinose, was assessed on the crystallization of gemcitabine hydrochloride (GHCl) in frozen solutions. Aqueous solutions containing GHCl (50mg/mL) and a sugar at varying concentrations (10–60mg/mL) were frozen in situ in DSC and analyzed in the subsequent heating run. Crystallization propensity of GHCl was quantified in terms of reduced crystallization temperature (RCT) as a function of sugar type and concentration. Multivariate analysis option in JMP® software was employed for calculating correlation between the variables. All sugars inhibited GHCl crystallization in a concentration dependent manner. At equal concentration, fructose (with the lowest Tg′) exerted the strongest inhibitory effect, whereas raffinose (with the highest Tg′) exerted the weakest inhibitory effect. Additionally, RCT showed a poor correlation with Tg′ (r=0.2327). Thus, the inhibitory effect of sugars could not be described by their anti-plasticization effect. This counter-intuitive behavior was explained by the inhibitory effect of sugars on ice crystallization, which increased the unfrozen water content (UWC) in the freeze concentrate, thereby lowering the supersaturation of GHCl. This was established by observing a good correlation (r=0.9666) between RCT and ln(1/UWC). Additionally, reduced diffusion kinetics of GHCl in presence of sugar molecules was also postulated. This study highlights the importance of unfrozen water towards governing the crystallization behavior of solutes in multi-component frozen systems.

Effect of Spray Drying Conditions on the Physicochemical Properties and Enthalpy Relaxation of α-Lactose

The purpose of this work was to investigate the effect of different spray drying conditions on the physicochemical properties of dried lactose. Results indicated that the feed concentration and inlet temperature, as well as storage condition, influenced the thermal properties of the dried material, which were evaluated by the degree of molecular relaxation, presumably associated to different levels of molecular mobility in the sample. It was evident that higher drying temperatures decreased molecular mobility of the dried material while increasing its glass transition and crystallization temperatures. This is most likely due to the existence of states of lower mobility within the material as those with higher mobility were relaxed. The change in heat capacity at the glass transition temperature, , and the reduced crystallization temperature, , were used to compare the crystallization tendencies of the spray dried powders. It was observed that a decrease in and an increase in were associated with higher crystallization temperatures. On the other hand, the enthalpic relaxation did not change significantly with storage conditions. The findings illustrated that the initial enthalpy relaxation, which occurred during spray drying, was related to the crystallization tendencies and storage conditions.

Unusual crystallization behavior in Ga-Sb phase change alloys

Combined in situ X-ray scattering techniques using synchrotron radiation were applied to investigate the crystallization behavior of Sb-rich Ga-Sb alloys. Measurements of the sheet resistance during heating indicated a reduced crystallization temperature with increased Sb content, which was confirmed by in situ X-ray diffraction. The electrical contrast increased with increasing Sb content and the resistivities in both the amorphous and crystalline phases decreased. It was found that by tuning the composition between Ga:Sb = 9:91 (in at.%) and Ga:Sb = 45:55, the change in mass density upon crystallization changes from an increase in mass density which is typical for most phase change materials to a decrease in mass density. At the composition of Ga:Sb = 30:70, no mass density change is observed which should be very beneficial for phase change random access memory (PCRAM) applications where a change in mass density during cycling is assumed to cause void formation and PCRAM device failure.

Improved leakage property and reduced crystallization temperature by V2O5 seed layer in K0.4Na0.6NbO3 thin films derived from chemical solution deposition

K0.4Na0.6NbO3 (KNN) thin films were prepared by chemical solution deposition. The V2O5 seed layer was introduced to modify the quality and electric properties of the thin films. The results show that the V2O5 seed layer can reduce the crystallization temperature to 425°C and largely improve the leakage property of the KNN thin films. The KNN thin film with 5nm thickness V2O5 seed layer exhibits high ferroelectric and dielectric properties (2Prmax=26μC/cm2, ε=796, tanδ=0.04) and low leakage current density (4.0×10−5A/cm2) at the electric field of 350kV/cm at room temperature. By adding the V2O5 seed layer, the conduction mechanism changes from SCLC mechanism to Ohmic mechanism in the lower electric field (<200kV/cm), and the Schottky emission mechanism is replaced by the Poole–Frenkel emission mechanism in the higher electric field (>200kV/cm).

The Effect of Water Plasticization on the Molecular Mobility and Crystallization Tendency of Amorphous Disaccharides

To study how water plasticization affects the molecular mobility and crystallization tendency of freeze-dried trehalose, sucrose, melibiose and cellobiose. Freeze-dried disaccharides were subjected to different relative humidity atmospheres and their physical stabilities were evaluated. Lyophilizate water sorption tendencies and glass transition temperatures were modeled using Brunauer-Emmett-Teller (BET) and Gordon-Taylor (GT) equations, respectively. Sucrose and cellobiose crystallization tendencies were compared by using the concept of reduced crystallization temperature (RCT), and the molecular mobilities of trehalose and melibiose were compared by measuring their T(1)H relaxation time constants. Based on the BET and GT models, water sorption tendency and the resulting plasticizing effect were different in sucrose when compared to the other disaccharides. Trehalose and melibiose exhibited generally slower crystallization rates when compared to sucrose and cellobiose. Amorphous melibiose was shown to be particularly stable within the studied water content range, which may have partly been caused by its relatively slow molecular mobility. Slow amorphous-to-crystalline transition rate is known to be important for lyoprotecting excipients when formulating a robust drug product. The physical stabilities of amorphous trehalose and melibiose even with relatively high water contents might make their use advantageous in this respect compared to sucrose and cellobiose.

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 p K 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.

Biodiesel production from mixtures of canola oil and used cooking oil

Abstract Used cooking oil (UCO) was mixed with canola oil at various ratios in order to make use of used cooking oil for production of biodiesel and also lower the cost of biodiesel production. Methyl and ethyl esters were prepared by means of KOH-catalyzed transesterification from the mixtures of both the oils. Water content, acid value and viscosity of most esters met ASTM standard except for ethyl esters prepared from used cooking oil. Canola oil content of at least 60% in the used cooking oil/canola oil feedstock is required in order to produce ethyl ester satisfying ASTM specifications. Although ethanolysis was proved to be more challenging, ethyl esters showed reduced crystallization temperature (−45.0 to −54.4 °C) as compared to methyl esters (−35.3 to −43.0 °C). A somewhat better low-temperature property of ester was observed at higher used cooking oil to canola oil ratio in spite of similar fatty acid compositions of both oils.

Thermal stability and magnetic properties of Gd–Fe–Al bulk amorphous alloys

Gd 65Fe 20Al 15, Gd 65Fe 15Al 20 and Gd 70Fe 15Al 15 bulk amorphous alloys were produced by copper mold casting method with the maximum diameters of 2, 1 and 1 mm, respectively. The crystallization temperature ( T x) and melting temperature ( T m) of the Gd 65Fe 20Al 15 bulk amorphous alloy are 808 and 943 K, respectively. Accordingly, the temperature interval of T m and T x, Δ T m (= T m − T x), is as small as 135 K and the reduced crystallization temperature ( T x/ T m) is as high as 0.86. The small Δ T m and high T x/ T m values are presumed to be the origin for the achievement of the high amorphous-forming ability of the Gd–Fe–Al bulk amorphous alloy. The Gd 65Fe 20Al 15, Gd 65Fe 15Al 20 and Gd 70Fe 15Al 15 bulk amorphous cylinders with a diameter of 1 mm exhibit superparamagnetism at room temperature, while the amorphous ribbon shows the paramagnetism at room temperature. Finally, the mechanical properties of Gd 65Fe 20Al 15 bulk amorphous alloys are investigated.

Effect of Ni addition on glass forming ability and thermal stability of Nd–Fe–Al–Ni bulk metallic glasses

(Nd 60Fe 30Al 10) 100− x Ni x (where x = 0, 3, 5, 8 and 10 at%) alloy cylinders with a diameter of 3 mm and a length of 55 mm were prepared by copper mold casting. The effect of Ni addition on glass forming ability (GFA) and thermal stability of Nd-based alloy was investigated using X-ray diffraction (XRD), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). It was found that a bulk metallic glass (BMG) composite with a small amount of primary crystallites in the amorphous matrix is formed without Ni addition, and the proportion of crystallites decreases with an increase in the amount of Ni. The (Nd 60Fe 30Al 10) 92Ni 8 alloy exhibits the best GFA even though there is no apparent glass transition and supercooled liquid region. It is interesting to note that the main melting temperature of the (Nd 60Fe 30Al 10) 92Ni 8 alloy is lower than its crystallization temperature, resulting in the value of the nominal reduced crystallization temperature T r ( =T x / T m ) being larger than 1.0. The separation of amorphous phases with different thermal stabilities is believed to be one of the reasons for the anomalous phenomenon. The high GFA of the alloy may be explained in terms of valence concentration and structural stability of the amorphous phase.

Glass formation and sluggish nucleation: Growth in ternary eutectic Co–Hf–B system

Four rapidly quenched (RQ) ribbons of Co–Hf–B alloys with the ternary eutectic compositions were obtained by melt-spinning. The thermal stability and glass forming ability (GFA) were studied using high-temperature differential scanning calorimetry (DSC) measurements. Very high GFA was found for all the alloys studied, which are characterized by high values (above 0.64) of the reduced crystallization temperature ( T rx = T x/ T m). The supercooled liquid region (Δ T x = T x − T g = 45 K) was found for Co 66Hf 6.5B 27.5 amorphous alloy with equilibrium microstructure composed of three intermetallic compounds (Co 2B, Co 21Hf 2B 6 and Co 3HfB 2). The high GFA was explained by the sluggish nucleation and slow growth of the complex structure intermetallic compounds in the ternary Co–Hf–B system. The Hf presence in the alloys studied plays an important role due to the slow diffusivity of relatively large atoms of this element.

Heating and cooling rate dependence of the parameters representing the glass forming ability in bulk metallic glasses

A GFA (glass-forming ability) indicator, reduced crystallization temperature ( T rx), has been suggested based on the consideration of both resistance of the amorphous phase against crystallization and stability of the under-cooled liquid against competing crystalline phase formation. The T rx parameter exhibits the best correlations with critical thickness ( Z c) and critical cooling rate ( R c) for glass formation when compared with those of Δ T x, T rg, and γ parameters. The T rx parameter obtained under higher scanning rate exhibits better linear regression fit with glass forming ability (GFA).