Residual Crystallinity Research Articles

An explorative analysis of process and formulation variables affecting comilling in a vibrational mill: The case of praziquantel

Praziquantel, a BCS II class anthelmintic drug used for the treatment of schistosome infections, was coground in a vibrational mill with different polymers (linear and crosslinked povidone, copovidone and sodium starch glycolate). An explorative analysis of formulation variables (drug-polymer wt ratio and polymer type) and process parameters (type of grinding media, grinding time and frequency) was carried out with the help of an experimental screening design. The influence of the above mentioned factors on three PZQ characteristics (residual crystallinity, water solubility enhancement and drug recovery) was studied. The variation of carrier amount proved to be by far the most important variable affecting all the experimental responses. A lower impact and, in some cases, rather null effect, had the variation of the process variables. All coground systems were characterized by a high amorphous degree and a solubility significantly higher than the API. A very promising product was obtained by processing at 20Hz for 4h, using 3 spheres of 15mm as grinding media, i.e. a coground having a 50% API content, showing a 4.6-fold greater solubility at 20°C than pure praziquantel. This product maintained the same antischistosomal activity of pure API and was both physically and chemically stable for at least 6 months.

Process analytical techniques for hot-melt extrusion and their application to amorphous solid dispersions.

Newly developed active pharmaceutical ingredients (APIs) are often poorly soluble in water. As a result the bioavailability of the API in the human body is reduced. One approach to overcome this restriction is the formulation of amorphous solid dispersions (ASDs), e.g., by hot-melt extrusion (HME). Thus, the poorly soluble crystalline form of the API is transferred into a more soluble amorphous form. To reach this aim in HME, the APIs are embedded in a polymer matrix. The resulting amorphous solid dispersions may contain small amounts of residual crystallinity and have the tendency to recrystallize. For the controlled release of the API in the final drug product the amount of crystallinity has to be known. This review assesses the available analytical methods that have been recently used for the characterization of ASDs and the quantification of crystalline API content. Well-established techniques like near- and mid-infrared spectroscopy (NIR and MIR, respectively), Raman spectroscopy, and emerging ones like UV/VIS, terahertz, and ultrasonic spectroscopy are considered in detail. Furthermore, their advantages and limitations are discussed with regard to general practical applicability as process analytical technology (PAT) tools in industrial manufacturing. The review focuses on spectroscopic methods which have been proven as most suitable for in-line and on-line process analytics. Further aspects are spectroscopic techniques that have been or could be integrated into an extruder.

May polypropylene films be a sufficiently effective functional barrier for foods packed in recycled paperboard and stored at room temperature?

Bags or films of biaxially oriented polypropylene (BOPP) are widely used for packing dry foods in paperboard boxes. At room temperature, BOPP films may perform adequately as functional barrier against the migration of substances from recycled paperboard into foods. However, among other factors, the barrier efficiency strongly depends on temperature. With a glass transition temperature of around 0 °C, it still has some residual crystalline structure, but gradually loses it with every degree of rising temperature. For example, we show that at 22 °C the barrier is about 4.5-times longer effective than at 28 °C. From our results we conclude that BOPP films optimized with regard to barrier properties may adequately protect packed food against contaminants from recycled paperboard for fairly long time periods, provided temperatures are in the lower range of room temperatures.

Dissolution behavior of co-amorphous amino acid-indomethacin mixtures: The ability of amino acids to stabilize the supersaturated state of indomethacin

Arginine, phenylalanine, and tryptophan have been previously shown to improve the solid-state stability of amorphous indomethacin. The present study investigates the ability of these amino acids to prolong the supersaturation of indomethacin in both aqueous and biorelevant conditions either when freely in solution or when formulated as co-amorphous mixtures.The co-amorphous amino acid-indomethacin mixtures (molar ratio 1:1) and amorphous indomethacin were prepared by cryomilling. Dissolution and precipitation tests were performed in buffer solutions (pH 5 and 6.5) and in Fed and Fasted State Simulated Intestinal Fluids (FeSSIF and FaSSIF, respectively). Precipitation tests were conducted with the solvent shift method. The supersaturation stability of indomethacin and the precipitation inhibitory effect of amino acids were evaluated by calculating the supersaturation factor and the excipient gain factor, respectively.Biorelevant media exerted a significant effect on indomethacin solubility but had little effect on the supersaturation stability. Arginine had the most significant impact on the dissolution properties of indomethacin, but also phenylalanine and tryptophan stabilized supersaturation in some media when formulated as co-amorphous mixtures with indomethacin. Only arginine stabilized supersaturation without co-amorphization, an effect only observed in media of pH 6.5. The unique behavior of the arginine-indomethacin mixture was further demonstrated by the abrupt formation of a precipitate, when an excess physical mixture of arginine and indomethacin was added to FeSSIF (pH 6.5). The solid-state investigation of this precipitate indicated that it probably consisted of crystalline arginine-indomethacin salt with possibly some residual crystalline starting materials.

Solid state amorphization of Mg-Zn-Ca system via mechanical alloying and characterization

Magnesium based bulk metallic glasses have attracted significant attention of researchers due to better mechanical and corrosion properties when compared to their crystalline counterparts especially for biomedical applications. Scaling up the part size and production volumes of such materials through liquid metallurgy route is challenging. In this work amorphous Ca5Mg60+xZn35−x (X=0, 3 and 7) alloys have been successfully synthesized through solid state amorphization using a high energy planetary ball mill. X-ray diffraction was used to identify the crystalline phases of the powder during reaction. Evolution of amorphous phase was analysed using a parameter involving the ratio of integral area of peaks to the integral area of background (IPB) obtained from XRD patterns. Results showed reaction time increases with decreasing Zn content in Ca5Mg60+xZn35−x (X=0, 3 and 7) alloy to obtain maximum amorphous structure with a small amount of residual crystalline phase. Prolonged milling of these powders, to eliminate residual crystalline phases, resulted in the nucleation of Mg102.08Zn39.6 phase. The composition dependent characteristic temperatures and thermal stabilities were studied using differential scanning calorimetry.

Utilization of ramon seeds (Brosimum alicastrum swarts) as a new source material for thermoplastic starch production

ABSTRACTThe development and characterization of biodegradable polymers deriving from renewable natural sources has attracted much attention. The aim of this work was to partially characterize a thermoplastic starch obtained from the starch of seeds from the ramon tree (TPS‐RS) as an option to substitute thermoplastic starch from corn (TPS‐CS), in some of its applications. At 55% of relative humidity (RH), TPS‐RS had higher tensile strength and deformation than TPS‐CS. X‐ray diffraction analysis showed similar values in residual crystallinity (percentage of crystallinity that remains after plasticization process) in both TPS. The SEM micrographs showed a few remnant granular structures in the TPS‐RS. The FTIR showed a greater intensity in band at 1016 cm−1 in the TPS‐CS and TPS‐RS in comparison with their corresponding native starch, indicating an increase in the amorphous region after plasticization. The TGA analysis showed greater thermal stability in TPS‐CS (340 °C) compared with TPS‐RS (327 °C). In addition, the glass transition temperature in both TPS was 24 °C. The results obtained represent a starting point to potentialize the use of TPS‐RS instead of TPS‐CS for the development of new biodegradable materials for practical applications in different areas. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44235.

Defect control of SiC polycrystalline fiber synthesized from poly-aluminocarbosilane

SiC-polycrystalline fiber (Tyranno SA) shows excellent heat-resistance up to 2000°C. Aiming to enlargement of the future application, increase in the mechanical strength of the fiber is eagerly required. Tyranno SA was produced via lots of heat-treatment procedure. This production process is very similar to that of carbon fiber containing decomposition and densification processes at high temperatures in inert gas atmosphere. As these production processes are accompanied by the gaseous by-products, it’s easy to remain pores in each filament along with some other defects. These pores would also become “defect” as well as both residual carbon and abnormal crystalline growth become remarkable defects. In this study, first, the relationship between the defect size and the tensile strength of SiC-polycrystalline fiber was obtained. From this result, it was clarified that the smaller the defect size became, the higher the strength became. By controlling the processes, smoother surface of SiC-polycrystalline fiber was obtained.

Relating residual stresses to machining and finishing in silicon carbide

Machining and surface finishing is essential in the processing of many ceramics, however, it can be detrimental to subsequent performance as it introduces residual stresses and structural defects. Using micro-Raman spectroscopy the residual stress and crystallinity of hot-pressed SiC tiles were examined after finishing with several different methods. 514nm and 633nm lasers in both conventional and confocal settings enabled stress as a function of depth to be assessed. Single crystal, electronics grade SiC was used for comparison. Compressive residual stresses were present at the surface and in the sub-surface region in all the samples, but the surface with lowest roughness and a mirror-like finish had the highest residual stress. Crystallinity in SiC is reduced by defects and stacking faults produced during machining and finishing. The finer surface finishes had higher residual stresses, but were actually found to have better crystallinity than the rough surfaces. The dependence of residual stress and crystallinity on surface roughness is attributed to a change in the mode of ceramic removal from energetic and brittle for rough finishes to ductile for the shallow cuts of smooth finishes. The dependence of stress and crystallinity on roughness means a balance must be struck between smoothness, crystallinity and stresses in choosing the best finish for a given application.

Differential scanning calorimetry predicts the critical quality attributes of amorphous glibenclamide

Selection of a crystallinity detection tool that is able to predict the critical quality attributes of amorphous formulations is imperative for the development of process control strategies. The main aim of this study was to determine the crystallinity detection tool that best predicts the critical quality attributes (i.e. physical stability and dissolution behaviour) of amorphous material. Glibenclamide (model drug) was milled for various durations using a planetary mill and characterised using Raman spectroscopy and differential scanning calorimetry (DSC). Physical stability studies upon storage at 60°C/0% RH and dissolution studies (non-sink conditions) were performed on the milled glibenclamide samples. Different milling durations were needed to render glibenclamide fully amorphous according to Raman spectroscopy (60min) and onset of crystallisation using DSC (150min). This could be due to the superiority of DSC (onset of crystallisation) in detecting residual crystallinity in the samples milled for between 60 and 120min, which were not detectable with Raman spectroscopy. The physical stability upon storage and dissolution behaviour of the milled samples improved with increased milling duration and plateaus were reached after milling for certain periods of time (physical stability — 150min; dissolution — 120min). The residual crystallinity which was detectable with DSC (onset of crystallisation), but not with Raman spectroscopy, adversely affected the critical quality attributes of milled glibenclamide samples. In addition, mathematical simulations were performed on the dissolution data to determine the solubility advantages of the milled glibenclamide samples and to describe the crystallisation process that occurred during dissolution in pH7.4 phosphate buffer. In conclusion, the onset of crystallisation obtained from DSC measurements best predicts the critical quality attributes of milled glibenclamide samples and mathematical simulations based on the solvent-mediated crystallisation model were successfully performed on the dissolution data.

Water and temperature contribution to the structuration of starch matrices in the presence of flavour

The effect of modulating the gelatinisation extent by hydration (50/50 and 80/20 water to starch ratio) and temperature (65 or 85°C) on various properties of wheat starch in presence of flavours has been studied. The hydrothermal treatments resulted in samples with different properties. The lowest residual flavour content was found in samples treated at the highest hydration and temperature (85°C) while the other treatment conditions led to samples with similar residual flavour content. Ethyl hexanoate significantly increased the characteristic pasting viscosities compared to starch±2-hexanone; suggesting a greater structuration with ethyl hexanoate. Heating starch in excess water caused amylopectin melting, but promoted an incomplete granular swelling as revealed by RVA. This study suggested that lowering the hydration upon treatment could limit both crystal melting (with a residual crystalline content up to 38% in the most extreme conditions) and granular swelling but increased granule organisation like following annealing.

Quantification of residual crystallinity in ball milled commercially sourced lactose monohydrate by thermo-analytical techniques and terahertz spectroscopy

The quantification of crystallinity is necessary in order to be able to control the milling process. The use of thermal analysis for this assessment presents certain challenges, particularly in the case of crystal hydrates. In this study, the residual crystallinity on ball milling of lactose monohydrate (LMH), for periods up to 90min, was evaluated by thermo-analytical techniques (TGA, DSC) and terahertz spectroscopy (THz). In general, the results from one of the DSC analysis and the THz measurements agree showing a monotonous decrease in relative residual crystallinity with milling time (∼80% reduction after 60min milling) and a slight increase at the 90min time point. However, the estimates from TGA and two other methods of analyzing DSC curve do not agree with the former techniques and show variability with significantly higher estimates for crystallinity. It was concluded that, the thermal techniques require more complex treatment of the data in the evaluation of changes in crystallinity of a milled material (in particular to account for the de-vitrification and mutarotation of the material that inevitably occurs during the measurement cycle) while the analysis of THz data is more straightforward, with the measurement having no impact on the native state of the material.

Fabrication and photocatalytic properties of Gd-doped ZnO nanoparticle-assembled nanorods

Gd-doped ZnO nanorods composed of nanoparticles were synthesized via an electrospinning combined with calcination route. It is revealed that the Gd-doped ZnO catalyst calcined at 500°C for a time of 7h shows the best photodegradation activity. A short calcination time of 1h gives rise to large amounts of residual carbon and low crystallinity of ZnO, which are adverse for charge separation. Increasing calcination time to 3h or 5h, suitable amounts of residual carbon that favors charge transfer plays a greater role than crystallinity. When the calcination time is further prolonged to 9h, a growth of nanoparticle size leads to a decreased photocatalytic performance. Thus, the efficiency for degradation activity is determined by the combinational effects of residual carbon, crystallinity and nanoparticle size.

Quantification of residual crystallinity of ball-milled, commercially available, anhydrous β-lactose by differential scanning calorimetry and terahertz spectroscopy

The quantification of crystallinity is necessary in order to be able to control the milling process. In this study, the changes in the amount of residual crystallinity of ball-milled anhydrous β-lactose (β-LA), for periods up to 60 min, were evaluated by differential scanning calorimetry (DSC) and by terahertz pulsed spectroscopy. The percentage of residual crystallinity using DSC was estimated by two methods: The first method was based on the measurement of the melting of the crystalline part, while the second was based on the measurement of the devitrification of the amorphous part. Peaks in THz spectra, related to the residual crystalline material were analyzed by two methods: (1) area under peak and (2) partial least square. The milled samples of β-LA show a monotonic decrease in crystallinity with milling time, although the quantitative analysis performed by different techniques reveals very different results. THz technique gives significantly lower estimates for % crystallinity (in the early time period) than that calculated from the DSC data, possibly because of the recrystallization of amorphous form during sample preparation. The comparison of residual crystallinity of β-LA with its hydrated counterpart [i.e., α-lactose monohydrate (α-LMH)] has shown that the amount of amorphous material produced from the α-LMH is 20–30 % greater than from β-LA at extended milling times (i.e. 60 min).

Quantitative Infrared Photoelasticity of Silicon Photovoltaic Wafers Using a Discrete Dislocation Model

Residual stress and crystalline defects in silicon wafers can affect solar cell reliability and performance. Infrared photoelastic measurements are performed for stress mapping in monocrystalline silicon photovoltaic (PV) wafers and compared to photoluminescence (PL) measurements. The wafer stresses are then quantified using a discrete dislocation-based numerical modeling approach, which leads to simulated photoelastic images. The model accounts for wafer stress relaxation due to dislocation structures. The wafer strain energy is then analyzed with respect to the orientation of the dislocation structures. The simulation shows that particular locations on the wafer have only limited slip systems that reduce the wafer strain energy. Experimentally observed dislocation structures are consistent with these observations from the analysis, forming the basis for a more quantitative infrared photoelasticity-based inspection method.

Effect of supercritical CO2plasticization on the degradation and residual crystallinity of melt-extruded spironolactone

Immediate-release solid dispersions of a slowly dissolving active pharmaceutical ingredient, spironolactone, were prepared by supercritical-CO2-assisted melt extrusion (a solvent-free and continuous manufacturing technology) using Eudragit E as matrix. Through optimizing process parameters (i.e. temperature, melt throughput, pressure and CO2 flow), stable foams with high porosity, homogeneous structure and thin (even submicronic) walls could be prepared, as revealed by scanning electron microscopy. The samples were found to be rigid enough to mill, enabling further processing, as is necessary to formulate tablets. The influence of extrusion temperature and melt throughput on residual drug crystallinity was measured using non-invasive confocal Raman mapping coupled with chemometric analysis, while the influence on the degree of drug degradation was determined using high performance liquid chromatography. The plasticizing effect of supercritical CO2 was shown to reasonably improve the purity of the prepared solid dispersions by enabling high-yield production at lower temperature ranges. At the same time, shorter residence time and lower temperature slightly increased residual drug crystallinity. The obtained foamy structures ensured immediate drug dissolution in an acidic medium. Copyright © 2014 John Wiley & Sons, Ltd.

Finite element analysis of laser shock peening of 2050-T8 aluminum alloy

Laser shock processing is a recently developed surface treatment designed to improve the mechanical properties and fatigue performance of materials, by inducing a deep compressive residual stress field. The purpose of this work is to investigate the residual stress distribution induced by laser shock processing in a 2050-T8 aeronautical aluminium alloy with both X-ray diffraction measurements and 3D finite element simulation. The method of X-ray diffraction is extensively used to characterize the crystallographic texture and the residual stress crystalline materials at different scales (macroscopic, mesoscopic and microscopic).Shock loading and materials’ dynamic response are experimentally analysed using Doppler velocimetry in order to use adequate data for the simulation. Then systematic experience versus simulation comparisons are addressed, considering first a single impact loading, and in a second step the laser shock processing treatment of an extended area, with a specific focus on impact overlap. Experimental and numerical results indicate a residual stress anisotropy, and a better surface stress homogeneity with an increase of impact overlap.A correct agreement is globally shown between experimental and simulated residual stress values, even if simulations provide us with local stress values whereas X-ray diffraction determinations give averaged residual stresses.

Predicting final product properties of melt extruded solid dispersions from process parameters using Raman spectrometry

Raman spectrometry was utilized to estimate degraded drug percentage, residual drug crystallinity and glass-transition temperature in the case of melt-extruded pharmaceutical products. Tight correlation was shown between the results obtained by confocal Raman mapping and transmission Raman spectrometry, a PAT-compatible potential in-line analytical tool. Immediate-release spironolactone–Eudragit E solid dispersions were the model system, owing to the achievable amorphization and the heat-sensitivity of the drug compound. The deep investigation of the relationship between process parameters, residual drug crystallinity and degradation was performed using statistical tools and a factorial experimental design defining 54 different circumstances for the preparation of solid dispersions. From the examined factors, drug content (10, 20 and 30%), temperature (110, 130 and 150°C) and residence time (2.75, 11.00 and 24.75min) were found to have significant and considerable effect. By forming physically stable homogeneous dispersions, the originally very slow dissolution of the lipophilic and poorly water-soluble spironolactone was reasonably improved, making 3minute release possible in acidic medium.

Functionalized celluloses and their nanoparticles: Morphology, thermal properties, and solubility studies

Agricultural residues derived cellulose was used to synthesize a new series of carboxy functionalized cellulosic nanoparticles (quasi-spherical shaped, 13.2–21.5% carboxyl content) and macro-sized 6-carboxycelluloses (long-fibril shaped, 1.7–22% carboxyl content). The DP (50–70) and yield (upto 46%) of nanoparticles were manipulated by controlling the reaction temperature and time. TGA/DTG thermographs of the carboxycelluloses gave thermostability data and co-related well with the residual crystalline, amorphous, and anhydroglucuronic acid content. The particle shape and size had no effect on the thermal stability. Some derivatives were fully or partially soluble in aqueous alkali and non-aqueous solvents, which can lead to increased versatility of these polymers.

Multiscale deconstruction of molecular architecture in corn stover.

Lignocellulosic composite in corn stover is a candidate biofuel feedstock of substantial abundance and sustainability. Its utilization is hampered by resistance of constituent cellulose fibrils to deconstruction. Here we use multi-scale studies of pretreated corn stover to elucidate the molecular mechanism of deconstruction and investigate the basis of recalcitrance. Dilute acid pretreatment has modest impact on fibrillar bundles at 0.1 micron length scales while leading to significant disorientation of individual fibrils. It disintegrates many fibrils into monomeric cellulose chains or small side-by-side aggregates. Residual crystalline fibrils lose amorphous surface material, change twist and where still cross-linked, coil around one another. Yields from enzymatic digestion are largely due to hydrolysis of individual cellulose chains and fragments generated during pretreatments. Fibrils that remain intact after pretreatment display substantial resistance to enzymatic digestion. Optimization of yield will require strategies that maximize generation of fragments and minimize preservation of intact cellulosic fibrils.

Effect of ball milling on structure and thermal stability of Al84Gd6Ni7Co3 glassy powders

The influence of ball milling on microstructure and thermal stability of the gas-atomized Al84Gd6Ni7Co3 glassy powder has been investigated as a function of the milling time. The results show that the traces of crystalline phases present in the as-atomized powder decrease gradually with increasing the milling time. The thermal stability of the fcc-Al primary phase increases while the thermal stability of the intermetallic phases decreases with increasing milling. Moreover, significant improvement in hardness occurs after milling, which is attributed to the amorphization of the residual crystalline phases present in the as-atomized powder. These results demonstrate that milling is an effective way for amorphizing the residual crystalline present in the amorphous matrix and to control the thermal stability of the material.