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Although the amount of amorphous content in lactose is low, its impact on the performance of a dry powder inhalation formulation might be high. Many formulators and regulatory agencies believe that the levels of amorphous content should be controlled once there is a relationship with the final product performance. This is however not an easy task. The current paper elaborates on multiple challenges and complexities that are related to the control of the amorphous content in lactose. The definition and quantification methods of amorphous lactose are reviewed, as well as challenges related to thermodynamic instability. Additionally, current monographs and recent position papers considering this parameter are discussed to provide an overview of the regulatory landscape. Development of a control strategy is recommended, provided that the amorphous content at a specific moment in the process has shown to have an impact on the performance of the dry powder inhaler.

In order to solve the problem that the glass forming ability of Al-based amorphous alloy is not easy to be evaluated because of the easy precipitation of α-Al crystal in the glass forming process,a simple and feasible glass forming ability evaluation scheme was designedto optimize the composition of amorphous AlNiZr alloy.Firstly,nine kinds of AlNiZr alloy ingots with different compositions were prepared; Then,under the same preparation conditions,the alloy ribbons with different compositions were prepared by single-roll strip casting method; Finally,the ribbons were characterized by XRD,and the amorphous content of alloy ribbon was calculated based on the XRD results.The results show that the glass-forming ability of Al100-x-yNixZry increases with the increase of Ni content and decreases with the increase of Zr content; When the Zr content is 3% and the Ni content is further increased to 20% and 25%,[JP2]the glass-forming ability of the alloy is reduced,and Al82Ni15Zr3 alloy has better glass-forming ability.By optimizing the compositions of amorphous AlNiZr alloy,a new evaluation scheme of glass-forming ability can be provided for the Al-based alloy without rare earth elements,and its application space in the field of equipment protection can be expanded.

This study examines the mechanical and tribological properties of FeCrMoCB amorphous coatings on AISI 52100 bearing steel using laser cladding (LC). Two samples with varying LC parameters were compared to uncoated polished steel. Analytical methods included scanning electron microscopy (SEM), X-ray diffraction (XRD), microhardness testing and tribological tests via a high-frequency reciprocating rig (HFRR) tribometer under both dry and lubricated conditions, were employed. Sample S1 exhibited a microhardness five times that of uncoated steel and a 95 % reduction in wear volume loss under dry conditions. Under grease-lubricated, S1 showed a 20 % reduction in the coefficient of friction and a 93 % reduction in wear volume loss. Sample S2 also outperformed uncoated steel. These results highlight the significant benefits of FeCrMoCB coatings. [Display omitted] [ABSTRACT FROM AUTHOR]

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The main purpose of this work is to evaluate which parameters obtained from the characterization of metakaolins (MKs) (physical, chemical, and mineralogical parameters) have greater relevance in terms of positive impact on concrete durability properties related to chlorides, and which scientific arguments support these results. In parallel, a comparative study between three different MKs was carried out to statistically evaluate the ability that each of these materials must modify and eventually improve concrete durability properties associated with chlorides (electrical resistivity and chloride migration). A discussion of the results was carried out considering evaluations of the microstructure, emphasizing the cementitious systems' porosity (by mercury intrusion porosimetry [MIP]). It was found that MKs contributed to reduced porosity and refined pores, which made the transport of chlorides significantly more complex, and that some characteristics of MK, especially its amorphous content, have been more decisive for that. [ABSTRACT FROM AUTHOR]

Medicine regulators require the melting points for crystalline drugs, as they are a test for chemical and physical quality. Many drugs, especially salt-forms, suffer concomitant degradation during melting; thus, it would be useful to know if the endotherm associated with melt degradation may be used for characterising the crystallinity of a powder blend. Therefore, the aim of this study was to investigate whether melt-degradation transitions can detect amorphous content in a blend of crystalline and amorphous salbutamol sulphate. Salbutamol sulphate was rendered amorphous by freeze and spray-drying and blended with crystalline drug, forming standards with a range of amorphous content. Crystalline salbutamol sulphate was observed to have a melt-degradation onset of 198.2±0.2°C, while anhydrous amorphous salbutamol sulphate prepared by either method showed similar glass transition temperatures of 119.4±0.7°C combined. Without the energy barrier provided by the ordered crystal lattice, the degradation endotherm for amorphous salbutamol sulphate occurred 50°C below the melting point, with an onset of 143.6±0.2°C. The enthalpies for this degradation transition showed no significant difference between freeze- and spray-dried samples (p>0.05). Distinct from convention, partial integration of the crystalline melt-degradation endotherm was applied to the region 193–221°C which had no contribution from the degradation of amorphous salbutamol sulphate. The linear correlation of these partial areas with amorphous content, R2=0.994, yielded limits of detection and quantification of 0.13% and 0.44% respectively, independent of drying technique. Melt-degradation transitions may be re-purposed for the measurement of amorphous content in powder blends, and they have potential for evaluating disorder more generally. [ABSTRACT FROM AUTHOR]

Fe-based amorphous coatings were prepared on the surface of the AISI 1020 steel pipe by high-speed laser cladding technique. This study is aimed to investigate the influence of scanning speed on the microstructure, hardness, amorphous content and corrosion resistance offered by the Fe-based amorphous coatings. The results showed that, the coating obtained at 50 mm/s exhibited a distinct three-layer hardness distribution, with the second layer displaying the highest hardness. This phenomenon was primarily ascribed to amorphous strengthening, fine-grain strengthening, and martensitic strengthening. The bottom region of the coatings contains budding crystals, with prominent aggregation of elemental Fe. Away from the budding regions, a transition from columnar to dendritic crystals was observed. The amorphous content of the coatings exhibited an initial rise followed by a decline with increasing scanning speed. Among these, the amorphous phase content of 130 mm/s coating was up to 95 %. Differential Scanning Calorimetry (DSC) test results confirmed the presence of amorphous phases in the bottom and middle regions of the 50 mm/s coating. Electrochemical experiments underscored the exceptional corrosion resistance of the 130 mm/s coating, evidenced by its maximum corrosion potential (−0.471 V), minimal corrosion current density (2.7 × 10−6 A/cm2), and highest polarization resistance value (22,149 Ω·cm2). This superior performance was attributed to the presence of the amorphous phase and the Cr oxide layer formed on the surface, providing robust protection to the substrate. • Fe-based amorphous coatings were prepared by high-speed laser cladding. • High hardness attributed to amorphous strengthening, fine-grain strengthening, and martensitic strengthening. • The amorphous content of the coatings increased initially but decreased at the highest scanning speed. • High amorphous content and the Cr oxide layer formed on the surface provided robust protection to the coating. [ABSTRACT FROM AUTHOR]

To investigate the effect of laser energy density on microstructure and properties, the Fe 41.5 Co 12.2 Cr 7.4 Mo 37.3 C 0.3 B 0.5 Y 0.4 Al 0.4 (at. %) amorphous coatings were fabricated by employing different laser energy density (10 J/mm2–60 J/mm2) via laser cladding technique. A detailed study was conducted on the microstructure, geometric morphology, amorphous content and properties of the coatings. It can be found that the Fe-based amorphous coatings mainly consist of amorphous and α-Fe, Fe 4 C, Fe 21 Mo 2 C 6 , M 23 (C, B) 6 phases. Meanwhile, as the laser energy density increases, the width and height of the geometric morphology are increased, which is the result of the Marangoni effect and the heat flux generated by laser energy. However, the corrosion resistance and microhardness display a decreasing trend, which can be attributed to the decrease in amorphous content. The cooling rates were decreased with increasing laser energy density, resulting in a negative correlation between laser energy density and amorphous content. • Various laser energy densities of Fe-based amorphous coatings were fabricated. • The phase composition of Fe-based amorphous coatings was studied. • Laser energy density affects the amorphous content and microstructure of coatings. • The properties of coatings with different energy densities were investigated. [ABSTRACT FROM AUTHOR]

A solid polymer electrolyte composed of poly(ethylene oxide) and sodium hexafluorophosphate has been synthesized with a varying fraction of succinonitrile via solution cast technique. Impedance spectroscopy, transference number measurements, and linear sweep voltammetry were used to study the electrochemical properties. The 10 wt.% succinonitrile system exhibited the highest ionic conductivity of ~ 2 × 10−5 S cm−1 which is two orders of magnitude higher than the pristine polymer salt system. The high ionic transference number (~ 1) confirms that ion conduction is dominated by ions and displays the voltage stability window of about 4 V. The dielectric permittivity and the relaxation time ( τ ε ′ , τ M , τ h ) values corresponding to the segmental motion of the polymer chain varies with the variation of succinonitrile content. The relaxation time and double-layer capacitance are in good agreement with the conductivity. Finally, an ion transport mechanism has been proposed to provide a better understanding of ion migration. [ABSTRACT FROM AUTHOR]

• Fe-based amorphous composite coatings with various amorphous contents were fabricated on 1045 steel via laser cladding. • Influence of laser power and scanning speed on the amorphous content and characteristics of the coatings were investigated. • Triobological properties of Fe-based amorphous composite coatings were studied under various sliding conditions and loads. • The wear mechanisms of the coatings with various amorphous contents were investigated. Fe-based amorphous composite coatings are promising surface coating materials, because of their low cost, high hardness, and superior wear resistance. In the present study, Fe-based composite coatings with various amorphous contents (35.9–59.3%) were deposited onto 1045 steel via laser cladding, and the influence of laser-cladding parameters on the amorphous content was analysed. The cross sections of the coating layer and ground coating surface were then characterised in terms of the microstructure, phase composition, amorphous content, grain size, and microhardness. Importantly, the tribological properties of coatings with various amorphous contents under both dry and lubricated sliding conditions with light and heavy loads were systematically investigated. The microstructure of the crystalline/amorphous mixture was found to be a function of the temperature gradient, cooling rate, and chemical composition. The high microhardness was related to the amorphous content and grain size. The tribological properties were found to be insensitive to the amorphous content under both dry and lubricated conditions under light and heavy loads. The manifold morphologies of the wear tracks and the transition of the wear mechanism were the result of the combined effects of the amorphous content, phase composition, and size and distribution of the crystalline phase. [ABSTRACT FROM AUTHOR]

Although the amount of amorphous content in lactose is low, its impact on the performance of a dry powder inhalation formulation might be high. Many formulators and regulatory agencies believe that the levels of amorphous content should be controlled once there is a relationship with the final product performance. This is however not an easy task. The current paper elaborates on multiple challenges and complexities that are related to the control of the amorphous content in lactose. The definition and quantification methods of amorphous lactose are reviewed, as well as challenges related to thermodynamic instability. Additionally, current monographs and recent position papers considering this parameter are discussed to provide an overview of the regulatory landscape. Development of a control strategy is recommended, provided that the amorphous content at a specific moment in the process has shown to have an impact on the performance of the dry powder inhaler., Competing Interests: The authors report there are no competing interests to declare., (© 2023 The Authors. Published by Elsevier B.V.)

Abstract The aim of this study was to enhance the kinetic solubility and dissolution rate of ibuprofen by co-milling with different excipients and to establish the underlying mechanism(s) for such enhancement. In the first-part, two excipients (HPMC and soluplus) were selected from seven, and the optimal ball-milling parameters of speed and time (18 Hz, 15 min) were determined based on solubility-enhancement and flow-ability criteria. In the second-part, co-milling of different weight-ratios of ibuprofen-to-excipient was carried out and solubility and dissolution rates were determined. Mechanisms of biopharmaceutical enhancement were studied by SEM, laser diffraction, DSC, and FTIR analysis of the co-mixtures. Ibuprofen solubility (0.09 mg/mL for un-milled) was increased by factors of 4–5 and 10–20 for HPMC and soluplus, respectively. The weakening of crystals, stabilization of the amorphous phase and an increase in solid-state hydrogen bonding are the likely mechanisms for this enhancement. Reductions in Q70% dissolution time were also observed, by a factor of 4 and 7 for ibuprofen:HMPC and ibuprofen:soluplus co-milled mixtures, respectively. Although, there were similar reductions in particle size, dispersibility and degree of amorphization in both mixtures, the higher dissolution rate for soluplus, over that for HPMC, must be due to the additional solubilization contribution to the kinetic solubility provided by soluplus. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Geopolymers are conventionally prepared from metakaolin, fly ash, or blast furnace slag. In this paper, geopolymer synthesis using two different red-clay ceramic powders and a varying amount of Na 2 O/SiO 2 activator is presented. Experimental results show that despite of the high content of crystalline minerals and lower concentration of amorphous matter, both tested precursors enable to prepare geopolymers with satisfactory mechanical properties. The discussion of measured values of compressive strength with respect to SiO 2 /Al 2 O 3 and Al 2 O 3 /(Na 2 O + K 2 O) ratios in the prepared geopolymer mixes reveals that the consideration of only amorphous portion of ceramics is appropriate. A higher content of CaO in the precursor is found to cause a broader pore size distribution and higher porosity of resulting geopolymers, which is due to the formation of calcium silicate hydrates. [ABSTRACT FROM AUTHOR]

While the incineration of biomass residues is gaining traction as a globally available source of renewable energy, the resulting ash is often landfilled, resulting in the disposal of what could otherwise be used in value-added products. This research focuses on the beneficial use of predominantly rice husk and sugarcane bagasse-based mixed biomass ashes, obtained from two paper mills in northern India. A cementitious binder was formulated from biomass ash, clay, and hydrated lime (70:20:10 by mass, respectively) using 2M NaOH solution at a liquid-to-solid mass ratio of 0.40. Compressive strength of the biomass ash binder increased linearly with compaction pressure, indicating the role of packing density. Between the two mixed biomass ashes used in this study, the one with higher amorphous content resulted in a binder with higher strength and denser reaction product. Multi-faceted characterization of the biomass ash binder indicated the presence of aluminum-substituted calcium silicate hydrate, mainly derived from the pozzolanic reaction. [ABSTRACT FROM AUTHOR]

Rice husk ash (RHA) produced without burning control presents atomic arrangements characteristic of quartz and cristobalite, and amorphous silica structure which interact with calcium hydroxide (CH) to form calcium silicate hydrate (C-S-H). The depolymerisation of amorphous silica and the following precipitation of hydrated compounds depend on the pH of the aqueous solution, controlled by the dissolution of CH. The use of RHA in the production of pozzolanic cement requires prior understanding regarding the interaction of pozzolan with CH without the presence of Portland cement. This system establishes the maximum consumption of lime per amorphous unit of RHA. In this work, mixtures simulating 15% and 25% partial replacement of Portland cement by RHA were investigated. The evolution of the pozzolanic activity up to 182 days was measured and indicates the existence of remaining CH in both pozzolanic systems, regardless of the RHA content. However, the reaction rate of the pozzolan was higher in the system with higher CH content. Lime fixed by pozzolanic activity is not dependent on the ratio between CH and pozzolan. [ABSTRACT FROM AUTHOR]

The production of rice-husk ash without controlled burning results in pozzolans with different physicochemical characteristics. The amorphous content of residual rice-husk ash (RRHA) is related to the temperature and exposure time during burning, whereas the BET specific surface area depends on the siliceous structure formed during plant growth, in addition to burning and grinding methods. In this study, amorphous content was quantified by X-ray diffraction (Rietveld refinement) in three RRHA samples randomly collected from rice mills located in southern Brazil, in which the burning process was not controlled. Pozzolanic activity evolution of RRHA samples in lime paste was monitored by thermogravimetry for 182 days in order to determine the influence of the lime:pozzolan ratio, BET specific surface area, and average particle size. The results show that lime consumption is not significantly affected by the BET specific surface area or average particle size of RRHA samples with a high amorphous content (>66%). The reaction rate of RRHA depends on the lime:pozzolan ratio. Lime consumption per unit surface area of RRHA declines with an increase in the BET specific surface area. Because the proposed shape factor connects the BET specific surface area and average particle size of RRHA and indirectly includes the amorphous content of RRHA samples, it can therefore be used as an indicator of RRHA reactivity. [ABSTRACT FROM AUTHOR]

In this work, multivariate statistical techniques are employed to determine patterns and conversion curves from time-resolved X-ray powder diffraction data. For these purposes, time-window statistical total correlation spectroscopy is introduced for the pattern matching of the crystalline phase and is shown to be effective even in the case of overlapping peaks. When combined with evolving factor analysis and multivariate curve resolution-alternating least squares, this technique allows a definite estimation of patterns and conversion curves. The procedure is applied to in situ synchrotron powder diffraction patterns to monitor the setting reaction of magnesium potassium phosphate ceramic (MKP) from magnesia (MgO) and potassium dihydrogen phosphate. It is shown that the phases involved in the reaction are clearly distinguished and their evolution is correctly described. The conversion curves estimated with the proposed procedure are compared with the ones determined with the peak integration method, leading to an excellent agreement (Pearson's correlation coefficient equal to 0.9995 and 0.9998 for MgO and MKP, respectively). The approach also allows for the detection and description of the evolution of amorphous phases that cannot be described through conventional analysis of powder diffraction data. [ABSTRACT FROM AUTHOR]

The role of KOH and NaOH as mineralisers in kaolinite-quartz (KQ) and kaolinite-quartz-feldspar (KQF) systems has been investigated, in order to determine how they affect the phase composition of ceramic bodies, and if they can replace traditional flux to boost formation of amorphous phases. Attention was paid to the effects induced by mineralisers on (i) the fundamental ceramic equilibrium reaction between crystal phases and amorphous phase, and (ii) on the morphology of the final ceramic product in terms of secondary mullite habit. NaOH and KOH turn out to be amorphous content boosters, but their efficiency to promote amorphous phases is related to quartz particle size, too. The amorphous component appears at the expenses of mullite and quartz, and an analysis of the formation Gibbs energy demonstrates that an increase in mineraliser content shifts the fundamental ceramic equilibrium reaction towards amorphous formation, though Na differs from K in affecting such transformation. [ABSTRACT FROM AUTHOR]

This study investigated the effect of the physicochemical properties of fly ash, including the particle sizes and chemical composition of the amorphous phase, on the compressive strength of high-volume fly ash mortars in which 50 vol.% of ordinary Portland cement was replaced with fly ash. The enhancement in the compressive strength of the high-volume fly ash mortars was observed due to the pozzolanic reaction after 7 days of hydration. This was found to depend on a combination of factors, including the content of amorphous SiO 2 and Al 2 O 3 , amorphous alkalinity, and surface area per volume of fly ash. [ABSTRACT FROM AUTHOR]

The main purpose of the study was to evaluate various pre-processing and quantification approaches of Raman spectrum to quantify low level of amorphous content in milled lactose powder. To improve the quantification analysis, several spectral pre-processing methods were used to adjust background effects. The effects of spectral noise on the variation of determined amorphous content were also investigated theoretically by propagation of error analysis and were compared to the experimentally obtained values. Additionally, the applicability of calibration method with crystalline or amorphous domains in the estimation of amorphous content in milled lactose powder was discussed. Two straight baseline pre-processing methods gave the best and almost equal performance. By the succeeding quantification methods, PCA performed best, although the classical least square analysis (CLS) gave comparable results, while peak parameter analysis displayed to be inferior. The standard deviations of experimental determined percentage amorphous content were 0.94% and 0.25% for pure crystalline and pure amorphous samples respectively, which was very close to the standard deviation values from propagated spectral noise. The reasonable conformity between the milled samples spectra and synthesized spectra indicated representativeness of physical mixtures with crystalline or amorphous domains in the estimation of apparent amorphous content in milled lactose. [ABSTRACT FROM AUTHOR]

The precipitation of struvite (MgNH 4 PO 4 ·6H 2 O) from waste streams has attracted considerable attention due to its potential for recovering phosphorus for fertilization. As struvite is primarily acquired by means of precipitation and crystallization from aqueous solutions, it is important to evaluate the roles of common metal ions, particularly those that are commonly found in wastewater, in the struvite crystallization process. This study was performed to quantitatively evaluate the effects of calcium and ferric ions on struvite crystallization using the Rietveld refinement method, which is based on the analysis of X-ray diffraction data. The results indicate that both calcium and ferric ions significantly inhibit the formation of struvite crystals, and the effects vary under different pH conditions. There was a negative linear correlation between the struvite weight content in the precipitates and the Ca/Mg molar ratio in the initial solution. However, ferric ions were confirmed to be a more efficient inhibitor of struvite crystallization. Ca 2+ and Fe 3+ further modified the needle-like struvite into irregular shapes. An unambiguous and quantitative understanding of the effects of foreign ions on struvite crystallization will help to reliably improve the quality of struvite products recovered from wastewater and the control of struvite deposits in water and sludge piping systems. [ABSTRACT FROM AUTHOR]

Ferric orthophosphate (FePO4) has had limited use as an iron fortificant in ready-to-eat (RTE) cereal because of its variable bioavailability, the mechanism of which is poorly understood. Even though FePO4 has desirable sensory properties as compared to other affordable iron fortificants, few published studies have well-characterized its physicochemical properties. Semi-crystalline materials such as FePO4 have varying degrees of molecular disorder, referred to as amorphous content, which is hypothesized to be an important factor in bioavailability. The objective of this study was to systematically measure the physicochemical factors of particle size, surface area, amorphous content, and solubility underlying the variation in FePO4 bioavailability. Five commercial FePO4 sources and ferrous sulfate were added to individual batches of RTE cereal. The relative bioavailability value (RBV) of each iron source, determined using the AOAC Rat Hemoglobin Repletion Bioassay, ranged from 51% to 99% (p < 0.05), which is higher than typically reported. Solubility in dilute HCl accurately predicted RBV (R2 = 0.93, p = 0.008). Amorphous content measured by Dynamic Vapor Sorption ranged from 1.7% to 23.8% and was a better determinant of solubility (R2 = 0.91; p = 0.0002) than surface area (R2 = 0.83; p = 0.002) and median particle size (R2 = 0.59; p = 0.12). The results indicate that while solubility of FePO4 is highly predictive of RBV, solubility, in turn, is strongly linked to amorphous content and surface area. This information may prove useful for the production of FePO4 with the desired RBV. [ABSTRACT FROM AUTHOR]

The effect of morphology and amorphous content, of three types of lactose, on the properties of ribbon produced using roller compaction was investigated. The three types of lactose powders were; anhydrous SuperTab21AN, α-lactose monohydrate 200 M, and spray dried lactose SuperTab11SD. The morphology of the primary particles was identified using scanning electron microscopy (SEM) and the powder amorphous content was quantified using NIR technique. SEM images showed that 21AN and SD are agglomerated type of lactose whereas the 200 M is a non-agglomerated type. During ribbon production, an online thermal imaging technique was used to monitor the surface temperature of the ribbon. It was found that the morphology and the amorphous content of lactose powders have significant effects on the roller compaction behaviour and on ribbon properties. The agglomerated types of lactose produced ribbon with higher surface temperature and tensile strength, larger fragment size, lower porosity and lesser fines percentages than the non-agglomerated type of lactose. The lactose powder with the highest amorphous content showed to result in a better binding ability between the primary particles. This type of lactose produced ribbons with the highest temperature and tensile strength, and the lowest porosity and amount of fines in the product. It also produced ribbon with more smooth surfaces in comparison to the other two types of lactose. It was noticed that there is a relationship between the surface temperature of the ribbon during production and the tensile strength of the ribbon; the higher the temperature of the ribbon during production the higher the tensile strength of the ribbon. [ABSTRACT FROM AUTHOR]

In a former publication the authors showed that low amounts of amorphous content (LOQ of 0.5%) in a hydrophobic model API (Ciclesonide) can be measured with an individually adjusted one-step dynamic organic vapor sorption (DVS). In this investigation the applicability is tested on various APIs which differ in lipophilicity (poor water solubility) and hygroscopicity (absorption of water). The vapor sorption method proved to be applicable in almost all cases. Moisture sorption isotherms were determined for all five investigated crystalline and amorphous APIs. However, it was necessary to select the parameters individually for each API. The used solvents (water, methanol, isopropanol and methylene chloride) and the humidity-levels (0.05 p / p 0 until 0.5 p / p 0 ) were chosen carefully because otherwise the amorphous amounts switch to their crystalline counterparts and are not detectable. The production of fully amorphous samples (absence of crystalline material measured by DSC, mDSC and XRPD) was optimized over several trials. As successfully methods proved ball-milling, freeze-drying, spray-drying and/or quench cooling. In the next step these fully amorphous amounts were blended with crystalline starting material to calibration curves (Turbula blender, influence of electrostatic charge to homogeneity) for the calculation of amorphous content. In summary, the following presented methods were used to determine and quantify low amorphous amounts (between 1.5% and 17.0%) in jet-milled powders (grinding pressure of 8 bar, 1–3 grinding cycles), respectively. [ABSTRACT FROM AUTHOR]

The effects of different manufacturing methods to induce formation of amorphous content, changes of physico-chemical characteristics of powder blends and changes of aerodynamic properties over storage time (6 months) analyzed with the Next Generation Impactor (NGI) are investigated. Earlier studies have shown that standard pharmaceutical operations lead to structural disorders which may influence drug delivery and product stability. In this investigation, fully amorphous drug samples produced by spray-drying (SD) and ball-milling (BM) as well as semi-crystalline samples (produced by blending and micronization) are studied and compared to fully crystalline starting material. The amorphous content of these hydrophilic and hydrophobic active pharmaceutical ingredients (APIs) was determined using a validated one-step DVS-method. For the conducted blending and micronization tests, amorphous amounts up to a maximum of 5.1% for salbutamol sulfate (SBS) and 17.0% for ciclesonide (CS) were measured. In order to investigate the impact of small amorphous amounts, inhalable homogenous powder mixtures with very high and low amorphous content and a defined particle size were prepared with a Turbula blender for each API. These blends were stored (6 months, 45% RH, room temperature) to evaluate the influence of amorphous amounts on storage stability. The fine particle fraction (FPF: % of emitted dose < 5 μm) was determined with the NGI at defined time points. The amorphous amounts showed a major effect on dispersion behavior, the mixtures of the two APIs showed differences at the beginning of the study and significant differences in storage stability. The FPF values for SBS decreased during storage (FPF: from 35% to <27%) for the blend with high amorphous amounts, in contrast the initially re-crystallized sample achieved a comparable constant level of about 25%. For the hydrophobic CS a constantly increasing FPF (from 6% to >15%) over storage time for both types of blends was determined. Therefore, prolonged stability of amorphous parts and an incalculable behavior for CS blends are supposed, in contrast, SBS showed a controllable FPF after conditioning. [ABSTRACT FROM AUTHOR]

The Fe-Cr-Mo-B-C coating was prepared on the 45 steel by laser cladding with different process parameters. The phase, morphology and microstructure of the obtained coatings were analyzed using X-ray diffraction (XRD), laser scanning microscope (LSM), scanning electron microscope (SEM) equipped with energy disperse spectroscopy (EDS), respectively. The influence of parameters on the crystallization, porosity, microhardness, wear resistance and corrosion resistance of the coatings was explored. As a result, the increase of laser power or overlap rate will cause more serious crystallization, porosity and even cracks, which can reduce the comprehensive properties of the coatings. The microhardness of the coatings is determined by the amorphous phase as well as the hard phase B 6 Fe 23 and Cr 2 B. By analyzing the performance of the coating, it is determined that the optimal conditions of the laser cladding is the power of 1400 W with the overlap rate of 30%. [ABSTRACT FROM AUTHOR]

Abstract: The so-called pharmaceutical solid chain, which encompasses drug substance micronisation to the final tablet production, at pilot plant scale is presented as a case study for a novel, highly potent, pharmaceutical compound: SAR114137. Various solid-state analytical methods, such as solid-state Nuclear Magnetic Resonance (ssNMR), Differential Scanning Calorimetry (DSC), Dynamic Water Vapour Sorption Gravimetry (DWVSG), hot-stage Raman spectroscopy and X-ray Powder Diffraction (XRPD) were applied and evaluated to characterise and quantify amorphous content during the course of the physical treatment of crystalline active pharmaceutical ingredient (API). DSC was successfully used to monitor the changes in amorphous content during micronisation of the API, as well as during stability studies. 19F solid-state NMR was found to be the method of choice for the detection and quantification of low levels of amorphous API, even in the final drug product (DP), since compaction during tablet manufacture was identified as a further source for the formation of amorphous API. The application of different jet milling techniques was a critical factor with respect to amorphous content formation. In the present case, the change from spiral jet milling to loop jet milling led to a decrease in amorphous API content from 20–30w/w% to nearly 0w/w% respectively. The use of loop jet milling also improved the processability of the API. Stability investigations on both the milled API and the DP showed a marked tendency for recrystallisation of the amorphous API content on exposure to elevated levels of relative humidity. No significant impact of amorphous API on either the chemical stability or the dissolution rate of the API in drug formulation was observed. Therefore, the presence of amorphous content in the oral formulation was of no consequence for the clinical trial phases I and II. [Copyright &y& Elsevier]

The current research focused on adjusting the low hydration activity of the metallurgical slag by phase reconstruction technique. Boron oxide was used as a phase regulator to improve the amorphous phase composition of the manganese slag, consequently enhancing its hydraulic activity. The effects of boron oxide dosage and calcination temperature on the manganese slag amorphous phase content were investigated. XRD and DTG were performed to analyze the hydration mechanism of the manganese slag powder and cement. Results show that, when boron oxide dosage is 15%, calcination temperature is 1 300 °C, and holding time for 1 hour, the amorphous content of the modified manganese slag reaches 95% and its 28-day activity index reaches 81.7%. The manganese slag powder can then be used as cement or concrete admixtures for the building materials industry. [ABSTRACT FROM AUTHOR]

Abstract: Starch has always been an important ingredient in human food, but increasingly it is being used for nonfood purposes. The amorphous content of starch granules is one of the major factors controlling food processing conditions and accounting for the quality of end products such as starchy foods and biodegradable plastics. However, the amorphous content of starch granules is usually estimated in an indirect fashion, by means of the determination of the degree of crystallinity. Here we show that due to the increased sensitivity of differential scanning calorimetry (DSC) at high scanning rates, (sometimes known as Hyper DSC), we can apply a direct method to quantify the amorphous content in waxy maize starch. These results show that Hyper-DSC has potential as a rapid and reliable technique to quantify the amorphous content of starch. [Copyright &y& Elsevier]

The purpose of this study was to determine the cause for flowability difference observed during drug product processing when different Metformin HCl drug substance batches of varying age were used. It was found that the lead time (age) between the final step (milling) in the manufacturing process of the Metformin HCl drug substance could be a factor. The lead time had an impact on flowability of Metformin/excipient blends during drug product processing even though these batches had no apparent differences in their release specifications. To study and understand the aging effect, two batches of Metformin HCl manufactured at different periods of time were selected. The surface energy values obtained by the density functional theory (DFT) method together with X-ray diffraction patterns, thermally stimulated current measurements, and dynamic vapor sorption isotherms indicated that the freshly manufactured Metformin HCl material contains detectable amounts of surface crystal defects, but are absent in aged sample, which could be the cause of flowability differences of Metformin/excipient blends observed during the drug product processing. Having identified the cause for different flow behavior, a method to destroy these defects was designed and the issue was resolved by rapid aging of Metformin HCl under humidity at room temperature. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:5030-5039, 2010 [ABSTRACT FROM AUTHOR]

Differential scanning calorimetry (DSC) is one of the most frequently used techniques for analyzing small concentrations of amorphous phases in a crystalline matrix. In recent years novel enhanced DSC approaches have been intensively looked for to improve parameters such as sensitivity, accuracy, and detection limit of the technique. Low levels of amorphous phases can be quantitatively determined in DSC by measuring the heat capacity change associated with the glass transition. In this short review the potentials provided by the HyperDSC and StepScan DSC techniques are discussed. Examples illustrate the advantages and disadvantages of the techniques and compare their abilities to detect small glass transitions and determine low contents of amorphous phases in samples which are mostly crystalline. [ABSTRACT FROM AUTHOR]

Abstract: α-Lactose monohydrate is widely used as an excipient in dry powder inhalers, and plays a very important role in the efficiency of the drug delivery. Due to the processing, low levels of amorphous lactose could be present in the blends. Varying amounts could have a strong effect on the efficiency of drug delivery of the powder blends. Therefore, the accurate measurement of low levels of amorphous lactose content is very important. A new method was developed to measure the amorphous content, based on dynamic vapour sorption (DVS). In contrast to the traditional re-crystallization approach of amorphous lactose, the new method is based on moisture sorption isotherms. Moisture sorption isotherms of blends of crystalline α-lactose and freeze-dried or spray-dried amorphous lactose were measured. By fitting the data with a Brunauer, Emmett, and Teller (BET) isotherm, a linear correlation was found between measured and actual amorphous content for the whole range of 0.1–100%. Differences between freeze-dried and spray-dried lactose, due to different molecular arrangements, could be removed by a preconditioning the samples at 35% RH prior to the isotherm measurement. It was shown that accurate determination of very low concentrations of amorphous lactose content is possible using moisture sorption isotherm analyses. [Copyright &y& Elsevier]

Abstract: Formulation of actives for pulmonary delivery with dry powder inhaler devices frequently requires a particle size reduction step. The high-energy forces imparted to a material during milling, as well as reducing particle size, can cause a significant change in physicochemical properties, in particular mechanical activation of the surface (manifested as generation of amorphous regions) which can affect formulated product performance. It is not clear whether particle size reduction occurs prior to, or concomitantly with, generation of amorphous content. In this study the formation of amorphous content with time in crystalline salbutamol sulphate was quantified with isothermal gas perfusion calorimetry as the sample was ball-milled. The data showed that the most particle size reduction occurred initially (d 0.5 dropping from 12.83±0.4 to 4.2±0.4 within 5min). During this time period, no detectable amorphous content was observed. Between 5 and 15min milling time the particle size distribution remained relatively constant but the amorphous content increased non-linearly with time. After 20min milling time the particle size increased slightly. The data suggest that particle size reduction occurs initially upon application of a force to the crystal. Once maximum particle size reduction has occurred the crystal absorbs the force being applied and the crystal lattice becomes disordered. After extended milling the conditions in the ball mill (heat and/or humidity) may cause crystallisation of some of the amorphous material resulting in particle–particle fusion. It would appear that the ball-milling process could be optimised to achieve the desired particle size distribution but without any loss of crystalline structure. [Copyright &y& Elsevier]

Despite the high sensitivity of isothermal calorimetry (IC), reported measurements of amorphous content by this technique show significant variability even for the same compound. An investigation into the reasons behind such variability is presented using amorphous lactose and salbutamol sulfate as model compounds. An analysis was carried out on the heat evolved as a result of the exchange of water vapor between the solid sample during crystallization and the saline solution reservoir. The use of saturated salt solutions as means of control of the vapor pressure of water within sealed ampoules bears inherent limitations that lead in turn to the variability associated with the IC technique. We present an alternative IC method, based on an open cell configuration that effectively addresses the limitations encountered with the sealed ampoule system. The proposed approach yields an integral whose value is proportional to the amorphous content in the sample, thus enabling reliable and consistent quantifications. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2080–2089, 2010 [ABSTRACT FROM AUTHOR]

Abstract: The use of a new sample holder for dynamic mechanical analysis (DMA) as a means to characterise the T g of powdered hydroxypropyl methyl cellulose (HPMC) has been investigated. A sample holder was constructed consisting of a rectangular stainless steel container and a lid engineered to fit exactly within the walls of the container when clamped within a TA instruments Q800 DMA in dual cantilever configuration. Physical mixtures of HPMC (E4M) and aluminium oxide powders were placed in the holder and subjected to oscillating strains (1Hz, 10Hz and 100Hz) whilst heated at 3°C/min. The storage and loss modulus signals showed a large reduction in the mechanical strength above 150°C which was attributed to a glass transition. Optimal experimental parameters were determined using a design of experiment procedure and by analysing the frequency dependence of T g in Arrhenius plots. The parameters were a clamping pressure of 62kPa, a mass ratio of 0.2 HPMC in aluminium oxide, and a loading mass of either 120mg or 180mg. At 1Hz, a T g of 177±1.2°C (n =6) for powdered HPMC was obtained. In conclusion, the new powder holder was capable of measuring the T g of pharmaceutical powders and a simple optimization protocol was established, useful in further applications of the DMA powder holder. [Copyright &y& Elsevier]

Abstract: Photocatalysts of nominal composition (Ti1− x Co x )O2− δ with 0.001⩽x⩽0.05 were prepared via a sol–gel technique followed by air firing (200–1000°C). The incorporation of cobalt inhibited crystal growth and slightly raised the anatase to rutile transformation temperature (∼700°C). An amorphous component was invariably significant with the maximum content (41–53wt%) appearing simultaneously with the removal of anatase, suggesting that rutile crystallizes via an aperiodic structure. While the introduction of cobalt shifted the apparent band gap to visible light energies this did not enhance performance as there was limited miscibility of cobalt in titania, non-catalytic secondary phases were present, and active Ti3+ sites were displaced by cobalt. [Copyright &y& Elsevier]

Abstract: Quantitative X-ray diffractometry using a Rietveld-based computational method (SIROQUANT™) has been carried out for a series of coal samples from the various Turkish mines. Standard proximate and ultimate analyses were carried out. Chemical compositions of the high-temperature ash (HTA) of coal samples were determined by X-ray fluorescence (XRF) spectrometry technique. Crystalline (mineral) matter and amorphous content of raw coal samples were estimated. The Ca, Si, Al, S and Fe concentrations are higher than those of the other major elements (Ti, Mn, Mg, Na, P, K) in the studied coal samples. The percentage of crystalline (mineral) matter for each sample varies from 16.5% to 36.1% of the coal samples. The minerals in the sampled coals consist mainly of quartz, clay minerals, calcite, pyrite, and gypsum. Percentages of crystalline (mineral) matter in ash content remarkably decrease for the Elbistan, Orhaneli, and Tufanbeyli lower-rank coals. [Copyright &y& Elsevier]

Abstract: Powder samples of ranitidine hydrochloride forms 1 and 2 were milled using a vibrational ball mill (Retsch MM301) for periods up to 240min at 4, 12 and 35°C. X-ray powder diffraction (XRPD), diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), solid-state nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC) were used to monitor solid-state properties of the milled samples. Milling of form 1 at 4°C led to a powder temperature of 36°C in the milling chamber and produced only amorphous drug; at 12°C (powder temperature 45°C) and at 35°C (powder temperature 62°C) progressive transformation of form 1 via amorphous drug to form 2 occurred. DSC of the milled samples showed a glass transition at 13–30°C and a crystallization exotherm (T c) between 30 and 65°C if the sample contained amorphous drug. The behaviour of the solid was speculated to be influenced by the relationship between powder temperature and T c; at powder temperatures below T c, amorphous drug is formed but no crystallization of form 2 occurs; at temperatures close to T c, amorphous content initially increases with transformation to form 2 on continued milling. At temperatures much higher than T c, at intermediate stages, less amorphous drug but both form 1 and form 2 are recovered, but continued milling gives only form 2. Form 2 did not transform to form 1 under any conditions used in this study. [Copyright &y& Elsevier]

A method was developed for the quantification of low levels of amorphous content in maltitol with StepScan DSC. The method was based on the fact that the change of specific heat at the glass transition is linearly proportional to the amorphous content. The influence of different measurement parameters of StepScan DSC was evaluated and two different calibration heating rates were tested. Synthetic mixtures with various proportions of crystalline and amorphous maltitol were prepared. Two different measurement methods were compared and the linear regression between Δ C p and amorphous content was obtained. The limit of detection (LOD) and the limit of quantification (LOQ) values were for the fictive temperature 0.24% (amorphous content) and 0.81% and for the half point temperature 0.27 and 0.92%, respectively, (method 1) and for the fictive temperature 0.18 (amorphous content) and 0.61% and for the half point temperature 0.16 and 0.52%, respectively (method 2). Very low determination limits for the quantification of amorphous content could be attained with the StepScan DSC method. However, the realistic limit of quantification was somewhat higher (about 3%) because of noise in the StepScan measurement. The main advantage of the StepScan DSC method for quantification of amorphous content was that the glass transition and relaxation peaks are separated into different curves and the interpretation becomes easier. [ABSTRACT FROM AUTHOR]

Abstract: A method was developed for the quantification of low levels of amorphous content in sucrose with hyperDSC. The method was based on the fact that the change of specific heat at the glass transition is linearly proportional to the amorphous content. It was found out that as annealing time increased, the glass transition temperature moved to a higher temperature and the change of specific heat increased. ΔC p for annealed totally amorphous sucrose was 0.761±0.012Jg−1 °C−1. Synthetic mixtures with various proportions of crystalline and amorphous sucrose were prepared. The following linear regression between ΔC p and amorphous content was obtained: ΔC p =0.0075x −0.00484 (R =0.999). The limit of detection (LOD) and the limit of quantification (LOQ) values were 0.062 and 0.207%, respectively. The effect of grinding time on the amorphous content of crystalline sucrose was studied and a correlation between grinding time and amorphous content of sucrose was found. It was also found that the amorphous content could only attain a value of about 80–90% by grinding in the way used in this study. [Copyright &y& Elsevier]

Abstract: Solution calorimetry can be used to determine the amorphous content of a compound when the solubility and dissolution rate of the compound in the chosen solvent are reasonably high. Sometimes, it can be difficult find a solvent in which a sample is freely soluble. The present study evaluated the use of solution calorimetry for the assessment of the amorphous content of a sample that is poorly soluble in a solvent. Physical mixtures of lactose and spray-dried lactose samples (the amorphous content varied from 0 to 100%) were analyzed by a solution calorimeter and the results were compared with Raman spectroscopy determinations. The heat of solvation of the samples was determined by solution calorimetry in organic solvents MeOH, EtOH, ACN, THF, acetone (400mg sample/100ml solvent). Lactose is virtually insoluble in ACN, THF and acetone and very slightly soluble in EtOH and MeOH. The amorphous content of the samples could not be determined by solution calorimetry in EtOH, ACN, THF or acetone. However, an excellent correlation was observed between the heat of solvation and the amorphous content of the samples in MeOH. Furthermore, the heat of solvation values of the samples in MeOH showed a linear correlation with the Raman quantifications. Therefore, our results demonstrate that solution calorimetry may represent a rapid and simple method for determining the amorphous content also in samples that are not freely soluble in the solvent. [Copyright &y& Elsevier]

Abstract: A Raman spectroscopy method was developed for the quantification of the amorphous content of lactose. Both physical mixtures and spray-dried samples were used and the results were compared with the IMC determinations. Sample inhomogeneities were averaged out by collecting multiple spectra from each sample, and the total measurement time remained below 10min due to the high sensitivity of the CCD-Raman spectrometer used in the measurements. The obtained calibration error (SEC) for the physical mixtures was 1.3% (w/w) in the 0–100% amorphous content range and was reduced to 0.2% (w/w) in the 0–10% range of more practical interest. The crystallization heat values of the spray-dried samples showed a linear correlation with the Raman quantifications in the amorphous content range of 0–80%, but saturated over the 80% concentration. This finding suggests a reference value of ca. 60J/g for the spray-dried samples, instead of the crystallization heat of amorphous lactose (ca. 50J/g) valid in the IMC determinations of physical mixtures. [Copyright &y& Elsevier]

Earlies studies suggest that solution calorimetry can be used to determine the extent of amorphous content of drug and excipient, when the solubility and dissolution rate of the compound in the chosen solvent are reasonably high. In the present study, the use of solution calorimetry for assessment of amorphous content of a sample that is not completely dissolved in a solvent was evaluated. Physical mixtures of lactose and spray-dried lactose samples were analysed. The amorphous content of the physical mixtures and the spray-dried samples varied from 0% to 100% determined by isothermal microcalorimetry. The enthalpy of solution(ΔsolH) was determined in water. The lactose samples were dissolved quickly in water. In addition, the enthalpy accompanied with an addition of a lactose sample in an over saturated aqueous solution(ΔsatH)(prepared from the corresponding lactose sample) was determined. The lactose sample did not completely dissolve in the over saturated aqueous solution. An excellent correlation was observed betweenΔsolH and the amorphous content of the samples. Interestingly, there was a linear correlation also betweenΔsatH and the amorphous content of the samples. Further, a linear relationship was observed between theΔsatH and theΔsolH of the samples. Therefore, solution calorimetry may represent a rapid and simple method for determining the amorphous content also in samples that are not completely dissolved in the solvent. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explore whether it is possible to use hyper differential scanning calorimetry (HDSC) to detect and quantify low levels of amorphous content in samples that are mostly crystalline. HDSC uses scan rates that are much faster than conventional DSC, and consequently results in greater sensitivity. It was found that with every increase in scan rate it became easier to detect the glass transition (Tg) response. Scanning at 500 °C/min was possible and this gave such great sensitivity that very low sample mass (ca. 1 mg) could be used without any loss in detection of Tg. Mixtures of crystalline and amorphous (spray dried) lactose were prepared and scanned at 500 °C/min. It was observed that the Tg response was easily detected even for samples that contained 1.5% amorphous content when using very low samples mass. The view held at present is that DSC is not well suited to studies of amorphous content if the sample contains 10% or less of the amorphous material. The data generated here show that much better detection sensitivity is possible when using the rapid scan rates. As well as being able to detect the presence of very low amorphous contents it was also possible to obtain a quantification, as a linear response was obtained for the step height change in heat flow as a function of amorphous content. It was concluded that HDSC provides a method of obtaining a very fast assessment of the presence of amorphous form, the possibility to quantify this and the need to use a very low sample mass. The combination of speed, low sample mass and sensitivity makes this a very valuable technique for studies on partially amorphous samples. [Copyright &y& Elsevier]