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The low oral bioavailability of active pharmaceutical ingredients in aqueous media causes to partial absorption through the gastrointestinal tract. Increasing surface area by particle size reduction has been accomplished to overcome these challenges. In this study, Aprepitant (APT) nanoparticles were prepared using a green solvent anti-solvent precipitation method based on subcritical water (SW) technology. Effects of three different parameters such as SW temperature (368.15–388.15 K), anti-solvent temperature (273.15–293.15 K), and polyethylene glycol concentration (0.02–0.04 wt%) were studied on the size and morphology of the produced nanoparticles. As the next step, optimization of the process was performed using the response surface Box-Behnken design (BBD), and optimum operational conditions were obtained as follows: SW temperature (388.15 K), anti-solvent temperature (283.15 K), and polyethylene glycol concentration (0.04 wt%). The results revealed a significant decline in the size of the precipitated particle by subcritical water-based technologies (5.0 nm, on average), as compared to the unprocessed drug particles (30 μm, on average). Green SW-based technologies are proposed for the preparation of APT nanoparticles with no requirement for organic solvents and post-processing purification stages. [Display omitted] • Drug original particles were nanosized using subcritical water anti-solvent technology, for the first time. • Influences of solvent temperature, anti-solvent temperature and PEG concentration were investigated. • Optimization of the process was performed using the response surface Box-Behnken design (BBD). • Mean particle size of aprepitant has been reduced from its original 30 μm to 5 nm. [ABSTRACT FROM AUTHOR]

In recent years, significant academic and commercial interest has focused on collagen derived from horse tendons, with potential applications across diverse sectors such as medicine, pharmaceuticals, and cosmetics. Nano collagen, with its enhanced wound penetration, improved cell contact, and heightened cellular regeneration and repair capabilities due to its high surface area, holds promise for a wide range of applications. In this study, we present a novel method for producing nano collagen from the equine tendon. Our approach is characterized by its speed, affordability, simplicity and environmentally friendly nature, with precise temperature - control to prevent collagen denaturation. We conducted a comprehensive characterization of the obtained samples, including assessments of morphology, chemical and thermal properties, particle size distribution and biocompatibility. Importantly, our results indicate improvements in thermal stability, and surface roughness of nano collagen, while preserving its molecular weight. These advancements expand the potential applications of nano collagen in various fields. [Display omitted] • Swift, cheap and environmentally conscious nano-sized collagen by ball milling • Effect of the mechanical treatment on the microstructure, size and thermal stability • Improvement in thermal stability and surface roughness of nano collagen • Increase of collagen application range guaranteed by the nanometric size [ABSTRACT FROM AUTHOR]

[Display omitted] • VBSS contains above 40% CaO which poses difficulty in recovering vanadium, hence parametric ball-milling was used. • Above 80% vanadium was effectively recovered with the low-temperature Na 2 CO 3(aq) MA-Leaching. • The MA parametric modeling integrated the chemical concentration into derivation for effective reactivity prediction. • The process is simple, low-temperature leaching, cost-effective, and eco-friendly. Powder formation using a ball mill has found applications in various industries such as extractive metallurgy, nanomaterials, chemicals, materials science, and pharmaceuticals, but the particle size reduction rate, speed, and milling/ignition time required for each industrial application are very crucial. A novel environmentally-friendly parametric modeling of wet ball-milling- Na 2 CO 3 (aq) leaching at low temperature without roasting operation was carried out to recover vanadium from vanadium-bearing steel slag (VBSS). The paradigm shift in the source of strategic metals (SMs) globally validates the fact that the gangue of today is the valuable mineral of tomorrow. Due to the depletion of primary resources, the world has shifted focus towards recovering SMs from secondary resources to cater to its upsurge demands and sustainability worldwide satisfactorily. VBSS has proven to be a promising secondary resource from which SMs especially vanadium can be recovered more economically and environmentally via mechanical activation-assisted leaching. In previous research works, a rigorous process (high temperature, high stirring speed pressure MA- leaching with/without roasting) has been used to recover vanadium from VBSS. This present research work investigated the effective processing of VBSS by paying meticulous attention to the processing parameters via particle size reduction (reactivity) equation derivation considering the chemical solution. A vanadium recovery efficiency above 80 % was achieved from VBSS at a reaction/milling time of 30 min, ball size 10 mm, BPR 7.8, speed 140 rpm, leaching time 2hrs, leaching temperature 80 °C–90 °C, and stirring speed 300 rpm. Generally, the experimental and derived theoretical model results follow the same trend in perfect agreement. [ABSTRACT FROM AUTHOR]

This study investigates the effects of particle size reduction at different inoculum-to-substrate ratios and nutrient media supplementation on the assessment of biomethane production from food waste, under batch mesophilic conditions. Two different food waste samples were used and the best method for testing biomethane potential was chosen based on their characterisation and methane yields. Results obtained indicate that Inoculum-to-substrate ratios of 3:1 and 4:1 helped to stabilise test reactors with smaller particle sizes of 1 mm and 2 mm, respectively. Consequently, an overall biomethane yield increase of 38% was reported (i.e., from 393 NmLCH 4 gVS−1 added to 543 NmLCH 4 gVS−1 added). This could potentially imply a better assessment of energy outputs from anaerobic digestion of food waste (i.e., 43.5% higher energy output as electricity from biogas, using commercial scale Combined Heat and Power (CHP) units). Although nutrient media supplementation did not enhance methane yield from optimum inoculum-to-substrate ratio (3:1) and particle size (1 mm), it was found that its application helped to stabilise food waste digestion by avoiding volatile fatty acids accumulation and high propionic-to-acetic acid ratio, consequently, improving the overall test kinetics with 91% lag time reduction from 5.6 to 0.5 days. This work supports the importance of key variables to consider during biomethane potential tests used for assessing methane yields from food waste samples, which in return can potentially increase the throughput of anaerobic digestion system processing food waste, to further increase the overall energy output. • Food waste particle size reduction enhanced material solubilisation. • Inoculum-to-substrate ratio selection depends on substrate's particle size. • Nutrient media supplementation helped to improve anaerobic digestion kinetics. • 38% increase in methane yield was achieved at 1 mm PS and 3:1 ISR. • Up to 43.5% increase in energy output as electricity was achieved. [ABSTRACT FROM AUTHOR]

Chalcogenide semiconductors are widely used, due to their versatile structural, optical and electrical properties. They are used in image sensors, energy conversion, non-volatile memory, and waveguides applications. Due to these versatilities in the properties, nanostructured thin films of TlInS 2 are successfully prepared by thermal evaporation. The average particle size changes due to thermal treatment are examined by X-ray diffraction (XRD), and transmission electron microscope (TEM). A sharp reduction in the average particle size of the pristine nanostructured films is reported upon annealing processes at 423 K and 523 K. Besides, thermal treatment temperatures induce changes in the dispersion parameters viz oscillator energy, dispersion energy, high-frequency dielectric constant and dielectric constant. Of these, only the oscillator energy decreases with the annealing temperatures while all the other parameters increase. Moreover, the non-linear optical calculations have revealed that the nanostructured TlInS 2 films exhibit high third-order nonlinear optical susceptibility of order 10 −11  esu and strong nonlinear refractive index of order 10 −10  esu. [ABSTRACT FROM AUTHOR]

Food binders must be sticky to glue different components together. This study evaluated the impact of homogenization of pea proteins on the stickiness of pea protein – apple pectin mixtures. A reduction in protein particle size was suggested to improve adhesion and cohesion by increasing reactive surface area, resulting in a sticky material. In addition, impact of concentrating methods, namely freeze-drying and vacuum evaporation, on concentrating the homogenized pea protein dispersions was investigated. A reduced particle size of pea proteins upon homogenization led to an increased stickiness of the biopolymer matrix when the proteins were vacuum evaporated as demonstrated by a tack test. This was attributed to a firmer and more cohesive bulk structure demonstrated by rheological, confocal laser scanning microscopy and visual observations. Vacuum evaporation prevented re-aggregation of protein particles compared to freeze-drying since less water was expelled during vacuum evaporation. These results provide new insights into tuning stickiness of biopolymer mixtures. • Homogenization of pea proteins reduced their particle size. • Vacuum evaporation maintained reduced particle size better than freeze-drying. • Pea protein-apple pectin blends with small particles were more cohesive & stickier. [ABSTRACT FROM AUTHOR]

Sediments link hillslopes to river channels. The size of sediments entering channels is a key control on river morphodynamics across a range of scales, from channel response to human land use to landscape response to changes in tectonic and climatic forcing. However, very little is known about what controls the size distribution of particles eroded from bedrock on hillslopes, and how particle sizes evolve before sediments are delivered to channels. Here we take the first steps toward building a geomorphic transport law to predict the size distribution of particles produced on hillslopes and supplied to channels. We begin by identifying independent variables that can be used to quantify the influence of five key boundary conditions: lithology, climate, life, erosion rate, and topography, which together determine the suite of geomorphic processes that produce and transport sediments on hillslopes. We then consider the physical and chemical mechanisms that determine the initial size distribution of rock fragments supplied to the hillslope weathering system, and the duration and intensity of weathering experienced by particles on their journey from bedrock to the channel. We propose a simple modeling framework with two components. First, the initial rock fragment sizes are set by the distribution of spacing between fractures in unweathered rock, which is influenced by stresses encountered by rock during exhumation and by rock resistance to fracture propagation. That initial size distribution is then transformed by a weathering function that captures the influence of climate and mineralogy on chemical weathering potential, and the influence of erosion rate and soil depth on residence time and the extent of particle size reduction. Model applications illustrate how spatial variation in weathering regime can lead to bimodal size distributions and downstream fining of channel sediment by down-valley fining of hillslope sediment supply, two examples of hillslope control on river sediment size. Overall, this work highlights the rich opportunities for future research into the controls on the size of sediments produced on hillslopes and delivered to channels. [ABSTRACT FROM AUTHOR]

The stirred media mill is a piece of process equipment used in comminution, which uses grinding media, beads of ceramic or similar material, to mediate energy transfer between a rotating impeller and a slurry of the particles to be ground. Motion of the media is vital to the action of the mill, but is often assumed to be simple in modelling due to incomplete knowledge in detail. The movement of a media particle in a stirred media mill has been observed using Positron Emission Particle Tracking. The occupancy and the kinetic energy of the particle within the mill have been calculated and plotted in order to examine the effect of tip speed on the particle. The particle path has been shown to be different below, at, and above the impellers indicating the media are subject to different forces in the region of the impellers. Changes in velocity of the particle correspond with changes of height of the particle in the mill, caused by the particle colliding with the impellers. The impeller speed was found to significantly affect media KE distribution in the mill. At higher tip speeds the media particle has lower energy outside the impeller zone compared to in the impeller zone indicating that there is significantly less energy transfer between the zones when the tip speed is increased. Additionally, at high tip speeds the occupancy is low in the high kinetic energy region at the impellers. [ABSTRACT FROM AUTHOR]

Nanocrystals have emerged as a potential formulation strategy to eliminate the bioavailability-related problems by enhancing the initial dissolution rate and moderately super-saturating the thermodynamic solubility. This review contains an in-depth knowledge of, the processing method for formulation, an accurate quantitative assessment of the solubility and dissolution rates and their correlation to observe pharmacokinetic data. Poor aqueous solubility is considered the major hurdle in the development of pharmaceutical compounds. Because of a lack of understanding with regard to the change in the thermodynamic and kinetic properties (i.e., solubility and dissolution rate) upon nanosizing, we critically reviewed the literatures for solubility determination to understand the significance and accuracy of the implemented analytical method. In the latter part, we reviewed reports that have quantitatively studied the effect of the particle size and the surface area change on the initial dissolution rate enhancement using alternative approaches besides the sink condition dissolution. The lack of an apparent relationship between the dissolution rate enhancement and the observed bioavailability are discussed by reviewing the reported in vivo data on animal models along with the particle size and food effect. The review will provide comprehensive information to the pharmaceutical scientist in the area of nanoparticulate drug delivery. [ABSTRACT FROM AUTHOR]

All- trans retinoic acid (ATRA) is a derivative of retinol (or vitamin A) presenting similar benefits but considerable lower adverse toxicity, mainly in cases of high or long-term therapeutic doses. ATRA showed to be effective in the treatment and/or chemoprevention of several epithelial and hematological malignancies and diverse dermatological and eye diseases however, its low solubility in aqueous media and photosensitivity hinder its wider usage by the conventional administration methods. Supercritical fluids technologies are being widely used to enhance the in vivo bioactivity of this type of drugs both by improving their dissolution rate (using particle size reduction processes) and/or by controlling their release into the media after incorporation into solid polymeric/inorganic matrices (using supercritical impregnation/foaming processes). In both cases the solubility of the drug in the supercritical fluid (usually scCO 2 ) is required for process optimization purposes. Therefore, in this work the solubility of ATRA in scCO 2 was measured at different isotherms (308.2, 318.2 and 328.2 K) and pressures that ranged from 10 up to 30 MPa using a static analytical method. Solubility data were correlated using three commonly used density-based models, namely the Bartle, Chrastil and Méndez-Santiago–Teja models. The solubility of ATRA in scCO 2 was found to be between 1.52 × 10 −6 and 1.84 × 10 −5 in terms of ATRA mole fraction and between 7.50 × 10 −3 and 1.07 × 10 −1 in terms of amount of solid solute per unit of volume of scCO 2 . Fairly good correlation agreement was obtained with all the applied models being the lowest deviations obtained with the Chrastil model. ATRA particles obtained after scCO 2 processing (dissolution in scCO 2 followed by re-precipitation) were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) and in vitro dissolution studies. The results showed that the processed particles maintained their chemical structure and presented enhanced dissolution in aqueous media (PBS:ethanol, 80:20, v/v) when compared with commercial (non-processed) ATRA. [ABSTRACT FROM AUTHOR]

This article reports on particle engineering by a top-down method involving organic solvent-free acoustic cavitation as a wet-grinding procedure. The effects of static and dynamic sonication on particle size reduction methods were compared to each other. The most effective process parameters were determined by a factorial design plan for the particle size distribution of an important active pharmaceutical ingredient, meloxicam, as response factor after sonication. Samples sonicated with appropriate process parameters were dried and investigated. Scanning electron microscopy images showed that the sonication resulted in a rounded shape and micronized size of the particles. Differential scanning calorimetry and X-ray powder diffraction examinations revealed the crystalline structure of the produced meloxicam by both sonication methods. Fourier transform infrared spectroscopy demonstrated that no chemical degradation occurred. Static sonication is recommended primarily for particle size reduction in preclinical samples, where the amount of the drug candidate is very small (e.g. nasal formulation), while dynamic sonication may be suitable for wet-grinding of different active substances to prepare pre-suspension (e.g. micronization and nanonization). [ABSTRACT FROM AUTHOR]

Incineration is an important municipal solid waste management process in Singapore. The incineration bottom ash (IBA) generated may contain heavy metals (HMs) and rare earth elements (REEs) that can cause environmental concerns upon reutilization. In this study, the particle size distribution, density, circularity, and chemical composition of the overall IBA as well as individual size ranges were determined. The particle size reduction characteristics and the mobility of HMs and REEs among different size ranges through ball milling and fluidization processes were examined. Certain HMs were found to present in high concentrations at particular particle size ranges. Mechanisms concerning the mobility of HMs and REEs were revealed. [ABSTRACT FROM AUTHOR]

To improve nanoconfinement of LiBH 4 and MgH 2 in carbon aerogel scaffold (CAS), particle size reduction of MgH 2 by premilling technique before melt infiltration is proposed. MgH 2 is premilled for 5 h prior to milling with LiBH 4 and nanoconfinement in CAS to obtained nanoconfined 2LiBH 4 –premilled MgH 2 . Significant confinement of both LiBH 4 and MgH 2 in CAS, confirmed by SEM–EDS–mapping results, is achieved due to MgH 2 premilling. Due to effective nanoconfinement, enhancement of CAS:hydride composite weight ratio to 1:1, resulting in increase of hydrogen storage capacity, is possible. Nanoconfined 2LiBH 4 –premilled MgH 2 reveals a single–step dehydrogenation at 345 °C with no B 2 H 6 release, while dehydrogenation of nanoconfined sample without MgH 2 premilling performs in multiple steps at elevated temperatures (up to 430 °C) together with considerable amount of B 2 H 6 release. Activation energy ( E A ) for the main dehydrogenation of nanoconfined 2LiBH 4 –premilled MgH 2 is considerably lower than those of LiBH 4 and MgH 2 of bulk 2LiBH 4 –MgH 2 (Δ E A = 31.9 and 55.8 kJ/mol with respect to LiBH 4 and MgH 2 , respectively). Approximately twice faster dehydrogenation rate are accomplished after MgH 2 premilling. Three hydrogen release ( T = 320 °C, P (H 2 ) = 3–4 bar) and uptake ( T = 320–325 °C, P (H 2 ) = 84 bar) cycles of nanoconfined 2LiBH 4 –premilled MgH 2 reveal up to 4.96 wt. % H 2 (10 wt. % H 2 with respect to hydride composite content), while the 1st desorption of nanoconfined sample without MgH 2 premilling gives 4.30 wt. % of combined B 2 H 6 and H 2 gases. It should be remarked that not only kinetic improvement and B 2 H 6 suppression are obtained by MgH 2 premilling, but also the lowest dehydrogenation temperature ( T = 320 °C) among other modified 2LiBH 4 –MgH 2 systems is acquired. [ABSTRACT FROM AUTHOR]

In this work we present a novel approach to model the micronization of pharmaceutical ingredients at process scales and times. 3D single-phase fluid-dynamics simulations are used to compute the gas velocity field within a spiral jet mill which are provided as input in a 1D compartmentalized model to calculate solid velocities along the radial direction. The particles size reduction is taken into account through a breakage kernel that is function of gas energy and local solid hold-up. Simulation results are validated against micronization experiments for lactose and paracetamol, comparing the model predictions with D10, D50 and D90 diameters values coming from Design of Experiments isosurfaces. The developed model allows for a fair estimation of the outlet particle size distribution in a short computational time, with very good predictions especially for D90 values. [Display omitted] • A novel decoupled model is developed to study spiral jet milling at process-scales. • The model exploits CFD simulations and 1D compartment-based calculations. • Breakage parameters were defined availing of ad hoc micronization experiments. • The proposed strategy works for brittle and semi-brittle substances. • Model predictions are in good accordance with experiments. [ABSTRACT FROM AUTHOR]

Abstract: Standard particle size reduction techniques such as high pressure homogenization or wet bead milling are frequently used in the production of nanosuspensions. The need for micronized starting material and long process times are their evident disadvantages. Combinative particle size reduction technologies have been developed to overcome the drawbacks of the standard techniques. The H 42 combinative technology consists of a drug pre-treatment by means of spray-drying followed by standard high pressure homogenization. In the present paper, spray-drying process parameters influencing the diminution effectiveness, such as drug and surfactant concentration, were systematically analyzed. Subsequently, the untreated and pre-treated drug powders were homogenized for 20 cycles at 1500bar. For untreated, micronized glibenclamide, the particle size analysis revealed a mean particle size of 772nm and volume-based size distribution values of 2.686μm (d50%) and 14.423μm (d90%). The use of pre-treated material (10:1 glibenclamide/docusate sodium salt ratio spray-dried as ethanolic solution) resulted in a mean particle size of 236nm and volume-based size distribution values of 0.131μm (d50%) and 0.285μm (d90%). These results were markedly improved compared to the standard process. The nanosuspensions were further transferred into tablet formulations. Wet granulation, freeze-drying and spray-drying were investigated as downstream methods to produce dry intermediates. Regarding the dissolution rate, the rank order of the downstream processes was as follows: Spray-drying>freeze-drying>wet granulation. The best drug release (90% within 10min) was obtained for tablets produced with spray-dried nanosuspension containing 2% mannitol as matrix former. In comparison, the tablets processed with micronized glibenclamide showed a drug release of only 26% after 10min. The H 42 combinative technology could be successfully applied in the production of small drug nanocrystals. A nanosuspension transfer to tablets that maintained the fast dissolution properties of the drug nanocrystals was successfully achieved. [Copyright &y& Elsevier]

Abstract: Particle size reduction is a crucial factor in transportation logistics as well as cellulosic conversion. The effect of particle size on enzymatic hydrolysis of pretreated Miscanthus x giganteus was determined. Miscanthus was ground using a hammer mill equipped with screens having 0.08, 2.0 or 6.0mm sieve openings. Particle size distribution and geometric mean diameters were determined for all samples. Ground samples were subjected to hot water, dilute acid or dilute ammonium hydroxide pretreatment. Enzyme hydrolysis was conducted on washed pretreated solids; sugar generation was used as a measure for pretreatment efficiency. Glucose and xylose concentrations were monitored using HPLC. Glucose and xylose profiles were generated and hydrolysis rates estimated. Glucose, xylose and total conversion yields were determined by comparing final sugar concentrations obtained to amounts present in pretreated biomass. Geometric mean diameters were the smallest from 0.08mm sieve screen (56μm) followed by 2.0mm (301μm) and 6.0mm (695μm) screens. An increasing trend in percent total conversion was observed with decreasing mean particle size. Across all pretreatments, biomass ground using 0.08mm screens resulted in highest total conversion. Enzyme hydrolysis of unpretreated biomass samples also resulted in increased total conversions as particle size decreased, although mean conversions (10–20%) were much lower than for pretreated biomass samples (53–94%), indicating the need for chemical pretreatments in biomass conversion. [Copyright &y& Elsevier]

Abstract: Particle size may significantly affect the speed and stability of anaerobic digestion, and matching the choice of particle size reduction equipment to digester type can thus determine the success or failure of the process. In the current research the organic fraction of municipal solid waste was processed using a combination of a shear shredder, rotary cutter and wet macerator to produce streams with different particle size distributions. The pre-processed waste was used in trials in semi-continuous ‘wet’ and ‘dry’ digesters at organic loading rate (OLR) up to 6kg volatile solids (VS) m−3 day−1. The results indicated that while difference in the particle size distribution did not change the specific biogas yield, the digester performance was affected. In the ‘dry’ digesters the finer particle size led to acidification and ultimately to process failure at the highest OLR. In ‘wet’ digestion a fine particle size led to severe foaming and the process could not be operated above 5kgVSm−3 day−1. Although the trial was not designed as a direct comparison between ‘wet’ and ‘dry’ digestion, the specific biogas yield of the ‘dry’ digesters was 90% of that produced by ‘wet’ digesters fed on the same waste at the same OLR. [Copyright &y& Elsevier]

Effects of forage family on rates of particle size reduction in, and passage from, the rumen and the relationship of these effects with preliminary dry matter intake (pDMI) were evaluated using 13 ruminally and duodenally cannulated Holstein cows in a crossover design with a 14-d preliminary period and two 18-d treatment periods. During the preliminary period, pDMI of individual cows ranged from 19.6 to 29.5 kg/d (mean = 25.9 kg/d). Experimental treatments were diets containing either a) alfalfa silage (AL) or b) orchardgrass silage (OG) as the sole forage. Silages were chopped to 10-mm theoretical length of cut and contained 42.3 and 58.2% neutral detergent fiber (NDF) for alfalfa and orchardgrass, respectively. Both diets contained approximately 25% forage NDF and 30% total NDF. Feed, orts, rumen, and duodenal samples were wet sieved to fractionate particles above (large) and below (small) 2.36 mm. Indigestible NDF (iNDF) was used as a flow marker. Preliminary DMI, an index of nutrient demand, was determined during the last 4 d of the preliminary period when cows were fed a common diet and used as a covariate. Main effects of forage family and their interaction with pDMI were tested by ANOVA. Approximately 75% of the NDF consumed was large and 25% was small for both treatments, but cows fed AL consumed more iNDF and less potentially digestible NDF (pdNDF) than cows fed OG. The AL diet increased the reduction rate (large to small) compared with OG despite less rumination per unit of forage NDF for AL than OG, suggesting alfalfa NDF was more fragile than orchardgrass NDF. Over 55% of particles in the rumen were below 2.36 mm for AL and OG, indicating that particle size was not a limiting constraint to passage. Passage rates (kp) of large iNDF and large pdNDF were similar for AL and OG, but AL increased kp of large pdNDF and OG decreased it as pDMI increased. The AL diet increased kp of small iNDF and small pdNDF compared with OG, resulting in lower rumen fill for AL than OG. The kp of small iNDF and small pdNDF were similar within forage family, suggesting buoyancy was not limiting passage. The OG diet increased rumen pool size of large NDF compared with AL, which likely retained small NDF, contributing to the slower kp of small iNDF and small pdNDF observed for OG. Particle size reduction was a prerequisite to ruminal passage but not a constraint. Selective retention of small particles was less for alfalfa than orchardgrass, resulting in lower rumen fill and less effective fiber. [ABSTRACT FROM AUTHOR]

Abstract: By controlling of two significant parameters mainly alkaline media concentration and temperature, magnetite nanoparticles were produced via coprecipitation method. Effect of named parameters on the particle size, size distribution and magnetic behaviour of particles were analyzed by means of X-ray diffraction spectroscopy (XRD), transmission electron microscopy (TEM), and vibrating sample magnetometry (VSM). To the best of our knowledge, there is no report on evaluation of sample preparation at room temperature and then post stirring at higher temperature on particle size and its magnetic properties. Results show the particles synthesized at elevated temperature (70¡C) and lower alkaline concentration (0.9M) have highest saturation magnetization, about 68 emu/gr at 70¡C, compared with 63 emu/gr at 25¡C and smallest particle size. [Copyright &y& Elsevier]

Abstract: One of the key factors in drug''s efficacy is the value of their bioavailability that increases by the reduction of particle size through improvement of dissolution rate. In this study, raloxifene particle size was reduced by Rapid Expansion of Supercritical Solution (RESS). The effect of extraction temperature (40–80°C), extraction pressure (10–18MPa) and spray distance (5–10cm) were investigated on size and particle size distribution of the nanoparticles. Particles were characterized using X-ray diffraction (XRD), Fourier Transform Infrared Analysis (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS). The average size of the unprocessed raloxifene particles was 45.28μm. After the process, depending on the experimental conditions, smaller particles were obtained, the smallest of which was 18.93nm. In addition, dissolution rate study indicated that a 7-fold increase in dissolution rate could be obtained by particle size reduction of raloxifene using RESS. Response Surface Methodology was used for the optimization of the results and showed that the smallest particle size could be achieved at temperature of 50°C, pressure of 17.7MPa and spray distance of 10cm. [Copyright &y& Elsevier]

Abstract: The dissolution properties of a drug and its release from the dosage form have a basic impact on its bioavailability. Solubility problems are a major challenge for the pharmaceutical industry as concerns the development of new pharmaceutical products. Formulation problems may possibly be overcome by modification of particle size and morphology. The application of power ultrasound is a novel possibility in drug formulation. This article reports on solvent diffusion and melt emulsification, as new methods supplemented with drying in the field of sonocrystallization of poorly water-soluble Gemfibrozil. During thermoanalytical characterization, a modified structure was detected. The specific surface area of the drug was increased following particle size reduction and the poor wettability properties could also be improved. The dissolution rate was therefore significantly increased. [Copyright &y& Elsevier]

Abstract: Particle size reduction is a suitable method to enhance the bioavailability of poorly soluble drugs. The reduction effectiveness depends on compound properties like crystallinity, hardness and morphology. Sometimes, it is difficult to obtain small particles. To solve this problem a combinative method was developed: a combination of freeze drying with high pressure homogenization (so-called H 96 process). The freeze drying modifies the drug structure to obtain a brittle, fragile starting material for the subsequent homogenization step. Screening experiments with glibenclamide have shown a relation between the lyophilization conditions and the final particle size. Systematic investigations using design of experiment (DoE) were conducted to identify optimal process parameters. The influence of the independent variables drug concentration and organic solvent composition during freeze drying were tested by conducting a two factorial design of experiment. The model drug was dissolved in mixtures of dimethyl sulfoxide (DMSO) and tert-butanol (TBA) in different concentrations, freeze dried and subsequently homogenized at high pressure. Using optimized process conditions the particle size after 20 cycles was very small: 164nm (z-average) and 0.114μm (d50%). On the contrary, with unmodified drug the results were 772nm (z-average) and 2.686μm (d50%). It was shown, that the structure modification of the drug by means of freeze drying can significantly improve the particle size reduction effectiveness of high pressure homogenization. The study confirmed also the usefulness of DoE for nanocrystal production. [Copyright &y& Elsevier]

Abstract: Salbutamol sulphate (SS) used in dry powder inhalers requires drug particles in the respirable size range of 1–5μm to achieve a suitable therapeutic effect. The aim of this study was therefore to determine strategies for controlling drug substance characteristics pre and post-crystallisation to facilitate the production of micronised SS with desirable particle attributes for optimal delivery as an inhaled aerosol. SS batches were crystallised using an antisolvent method to produce a range of crystal morphologies. Air jet milling was then used to reduce the size of crystallised SS particles. Starting materials and micronised batches of SS were characterised in the solid state using a range of techniques with subsequent assessment of aerosol properties. Assessment of the aerodynamic characteristics of micronised SS delivered by DPI (without any carrier) indicated that fine particle fraction and emitted dose as a percentage of the total recovered dose were dependent on the quality attributes of the micronised SS, which were directly linked to the degree of imperfections and the morphology of the crystalline feedstock used in micronisation. Aerosolization performance of micronised SS can be optimised by manipulation of feedstock characteristics through crystal engineering and through definition of optimal processing conditions for micronisation. [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]

Abstract: Jet milling is commonly used for reducing the particle size of active pharmaceutical ingredients. Unfortunately, this process is sometimes difficult to control as pre-existing flaws and mechanical properties affect the particle fracture behaviour in a mill. In this study the effect of pre-existing flaws on mechanical material properties of crystals of a model material, sodium chloride, from different sources have been investigated using optical microscopy, nanoindentation, and powder compaction. Subsequently, these properties have been correlated with particle fracture in a jet mill. The paper shows that particles that have a small average flaw size possess the lowest constraint factor (i.e. the constraint factor is defined as the ratio of the hardness and the yield pressure and is an expression of the ductility of the material) whereas particles that have a large average flaw size have a high constraint factor and hence behave more ductile. Moreover, the study shows that the rank orders of the mechanical properties are consistent with the rank order of the experimentally determined particle rate of breakage. Materials that have a relatively low hardness show the highest particle rate of breakage. The degree of particle fracture during jet-milling tends to decrease for particles that have a smaller flaw density and behave more ductile. The paper shows that pre-existing flaws have an impact on mechanical properties and on particle fracture behaviour in a jet mill. It is concluded that the increase of the particle rate of breakage as a function of particle size is influenced by the number of flaws rather than by flaw length. [Copyright &y& Elsevier]

Abstract: Using a LEITZ-II thermal microscope, thermal expansion characteristics of quartzite particles with different proportions of silicon dioxide (SiO2) were investigated at temperatures ranging from room temperature to 1600°C. The experimental results showed that the thermal expansion of the quartzite particles with the temperature can be divided into three temperature regions, namely: the slow-expansion region, the temperature-independent region where the linear expansion coefficient tends to be zero and the fast-expansion region with a sharp wave crest. A particle with high proportion of SiO2 (high purity particle) has higher melting characteristic temperatures and higher starting temperature of the fast-expansion region. In addition, the microstructure of high purity quartzite particles heated to different terminal temperatures were also observed through a HITACHI scanning electron microscope (SEM). Lots of micro-cracks (∼10μm wide on the sample surface and ∼1μm wide inside the sample) can be formed at temperatures exceeding the starting temperature of the fast-expansion region. Calculating the residual deformations of the cooled particles which had been heated up to the different terminal temperatures indicated that these micro-cracks can greatly weaken the elasticity of the quartzite particles. [Copyright &y& Elsevier]

Abstract: Several sample preparation techniques were evaluated for extracting active pharmaceutical ingredient (API) from immediate release (IR) and controlled release (CR) tablet formulations. These techniques utilized either elevated temperature [e.g., accelerated solvent extraction (ASE) and microwave assisted extraction (MAE)] or particle size reduction [e.g., ball mill and homogenizer/Tablet Processing Workstation II (TPWII)]. Results were compared for equivalence to those obtained with the existing standard method for each formulation. For the CR formulations, sample preparation times were significantly reduced when using these techniques compared to the standard method. Advantages and limitations associated with each technique are discussed. [Copyright &y& Elsevier]

Abstract: The oral bioavailability of EMD 57033, a calcium sensitizing agent with poor solubility, was compared in dogs using four solid dosage form formulation approaches: a physical blend of the drug with excipients, micronization of the drug, preparation of coground mixtures and spray-drying of the drug from a nanocrystalline suspension. The formulations contained generally accepted excipients such as lactose, hydroxypropylmethyl cellulose and sodium lauryl sulphate in usual quantities. Drug micronization and cogrinding was realized by a jet-milling technique. Nanoparticles were created by media milling using a bead mill. All formulations were administered orally as dry powders in hard gelatine capsules. While micronization increased the absolute bioavailability of the solid drug significantly compared to crude material (from nondetectable to 20%), cogrinding with specific excipients was able to almost double this improvement (up to 39%). With an absolute bioavailability of 26%, spray-dried nanoparticular EMD 57033 failed to show the superior bioavailability that had been anticipated from in vitro data. The control solution prepared with cyclodextrin was shown to have an absolute bioavailability of 57% (vs. i.v. infusion). It was concluded that cogrinding can be a useful tool to improve the bioavailability of poorly soluble drugs from a solid dosage form format. [Copyright &y& Elsevier]

Abstract: The rate of the dissolution of four poorly soluble drugs (EMD 57033, albendazole, danazol and felodipine) was improved by cogrinding them with various excipients (lactose monohydrate, corn starch, polyvinylpyrrolidone, hydroxypropylmethyl cellulose and sodium lauryl sulphate) using a jet-milling technique. Solid state characterization studies by X-ray diffraction and differential scanning calorimetry verified the maintenance of the crystalline state of the active substances after milling. In vitro dissolution of the coground mixtures in biorelevant media was much faster than from micronised drug in the corresponding physical mixtures for all four compounds. Supersaturated solutions were generated in some cases (EMD 50733 and felodipine), but this phenomenon appeared to be drug- and excipient-specific. Cogrinding with lactose monohydrate resulted in fast dissolution with unstable supersaturation for EMD 57033. Cogrinding the same drug with PVP or HPMC produced a more sustained supersaturation. SLS accelerated the dissolution of EMD 50733 but inhibited supersaturation. The results suggest that the cogrinding with selected excipients is a powerful tool to accelerate the dissolution of poorly soluble drugs without converting the drug to the amorphous form or changing the particle size. [Copyright &y& Elsevier]

Abstract: Several techniques were compared for improving the dissolution of fenofibrate, a poorly soluble drug. Particle size reduction was realized by jet milling (micronization; cogrinding with lactose, polyvinylpyrrolidone or sodium lauryl sulphate) and by media milling using a bead mill (nanosizing) with subsequent spray-drying. Solid state characterization by X-ray diffraction and Differential Scanning Calorimetry verified the maintenance of the crystalline state of the drug after dry milling and its conversion to the amorphous state during spray-drying. Micronization of fenofibrate enhanced its dissolution rate in biorelevant media (8.2% in 30min) compared to crude material (1.3% in 30min). Coground mixtures of the drug increased the dissolution rate further (up to 20% in 30min). Supersaturated solutions were generated by nanosizing combined with spray-drying, this process converted fenofibrate to the amorphous state. Fenofibrate drug products commercially available on the German and French markets dissolved similarly to crude or micronized fenofibrate, but significantly slower than the coground or spray-dried fenofibrate mixtures. The results suggest that cogrinding and spray-drying are powerful techniques for the preparation of rapidly dissolving formulations of fenofibrate, and could potentially lead to improvements in the bioavailability of oral fenofibrate products. [Copyright &y& Elsevier]

Abstract: The purpose of the present study was to investigate the effects of particle size on the dissolution and oral absorption of cilostazol. Three types of suspensions having different particle size distributions were prepared of the hammer-milled, the jet-milled cilostazol crystals and the NanoCrystal® spray-dried powder of cilostazol. In vitro dissolution rate of cilostazol was significantly increased by reducing the particle size. The dissolution curves of the cilostazol suspensions were in good agreement with the simulation based on the Noyes–Whitney equation. The bioavailability of cilostazol after oral administration to dogs was increased with reducing the particle size. While positive food effect on the absorption was observed for the suspensions made of the hammer-milled and the jet-milled crystals, no significant food effect was found for the suspension made of the NanoCrystal® cilostazol spray-dried powder. These results could be qualitatively predicted from the in vitro dissolution data using the bio-relevant media, FaSSIF and FeSSIF. In conclusion, the NanoCrystal® technology is found to be efficient to improve the oral bioavailability of cilostazol and to avoid the food effect on the absorption. [Copyright &y& Elsevier]

[Display omitted] The novel particle generation processes of Active Pharmaceutical Ingredient (API)/drug have been extensively explored in recent decades due to their wide-range applications in the pharmaceutical industry. The Rapid Expansion of Supercritical Solutions (RESS) is one of the promising techniques to obtain the fine particles (micro to nano-size) of APIs with narrow particle size distribution (PSD). In RESS, supercritical carbon dioxide (SC CO 2) and API are used as solvent and solute respectively. In this literature survey, the application of RESS in the formation of fine particles is critically reviewed. Solubility of API in SC CO 2 and supersaturation are the key factors in tuning the particle size. The different approaches to model and predict the solubility of API in SC CO 2 are discussed. Then, the effect of process parameters on mean particle size and the particle size distribution are interpreted in the context of solubility and supersaturation. Furthermore, the less-explored applications of RESS in preparation of solid-lipid nanoparticles, liposome, polymorphic conversion, cocrystallization and inclusion complexation are compared with traditional processes. The solubility enhancement of API in SC CO 2 using co-solvent and its applications in particle generation are explored in published literature. The development and modifications in the conventional RESS process to overcome the limitations of RESS are presented. Finally, the perspective on RESS with special attention to its commercial operation is highlighted. [ABSTRACT FROM AUTHOR]

[Display omitted] • Pretreatment of cotton and linen powders with two ultrasonic devices was tested. • The individual contribution of ultrasound to the enzymatic digestion was evaluated. • Enrichment of the smallest particles with increased accessibility was observed. • The enzyme preferably digested the small particles resulting in a high sugar yield. • The new particle size distribution curves shifted towards the larger size regions. The contribution of ultrasound-aided particle size reduction to the efficiency of the subsequent enzymatic hydrolysis and the accompanying morphological changes of bleached cotton and linen powders were investigated. The aqueous suspensions of cellulosic powders were pretreated either with an ultrasonic bath (US-B) or with a horn-type reactor (US-H). Results revealed that the impact of US-H was more pronounced than that of the US-B. Clearly, the linen particles were more sensitive to ultrasonication than cotton. The US-H modified the particle size distribution differently for the cotton and linen powders and reduced the mean size of particles from 49 to 40 µm and from 123 to 63 µm, respectively. A significant increase in the water retention and water sorption capacity was also measured. The smaller particles with increased accessibility were preferably digested in the enzyme treatment, resulting in a considerably higher concentration of reducing sugars and an enrichment of the residual particles with a larger average size (cotton: 47 µm; linen: 66 µm). [ABSTRACT FROM AUTHOR]

[Display omitted] The aim of this work was to strengthen the understanding of the intensified vibratory mill by unravelling the milling process in terms of the particle size reduction and heat generation via a modern design of experiments approach. Hence, the influence of five process parameters (acceleration, breaks during milling, bead size, milling time and bead-suspension ratio) was investigated via an I-optimal design. Particle size was measured via laser diffraction and the temperature of the sample after milling was computed. To advance our understanding, a mechanistic model for the set-up of wet-stirred media milling processes was applied on the observed milling trends. A generic approach for the optimisation of the milling process was retrieved and included the optimisation of the bead size and intermittent pausing for effective cooling. To finetune the remaining process parameters, the present work provides contour plots and strong predictive models. With these models, the particle size and the temperature after milling of suspensions manufactured with the intensified vibratory mill could be forecasted for the first time. [ABSTRACT FROM AUTHOR]

Abstract: This short paper is a personal account of the development of techniques to enhance the bioavailability of a series of poorly soluble drugs by particle size reduction to the nanometer size range. This is a nanotechnological approach which has come of age and has had a practical impact on drug delivery. The drug is in effect the nanosystem. [Copyright &y& Elsevier]

• Reduction of Cu-BTC particles size was done by three-layer synthesis method. • Pure and binary gas permeation behavior for He/CH 4 and He/N 2 was investigated. • Interface compatibility of MMMs was enhanced by addition of size-reduced particles. • Both permeability and selectivity are improved by adding MOF into Matrimid. • The MMM with 40 wt% Cu-BTC successfully surpassed the 1991 Robeson's upper bound. Preparation of mixed matrix membranes (MMMs) with appropriate separation efficiency requires tenacious interfacial affinity between filler particles and polymer matrix. In this work, Cu-BTC particles with two structures of size-reduced and needle were successfully synthesized via the three-layer synthesis approach and combined with Matrimid to prepare MMMs for helium separation. Extensive characterization of particles (XRD, SEM, TGA, FTIR and N 2 sorption) and membranes (SEM, TGA, DSC and density-FFV measurements) were performed to gain insight in the membranes separation behavior. Then gas separation performance of membranes were examined for the single gases He, CH 4 and N 2 and the gas mixtures He/CH 4 and He/N 2. The combination of MOFs with Matrimid resulted in an increase in T g , density and degradation behavior of MMMs indicating a good compatibility between the fillers and polymer, however this development is more pronounced for reduced particles. The MMMs containing size-reduced MOF had premiere gas separation performance in comparison with the needle particles and overcame the 1991 Robeson upper bond. The MMM at 40 wt% loading exhibited the best efficiency with He permeability of 66.4 Barrer which is about three times more than pure Matrimid. In addition, the improvements in He/CH 4 and He/N 2 ideal selectivities were 181 and 169%, respectively. Mixed gas permeability measurements showed that helium permeability values and also selectivities decreased slightly compared to single gas data due to the competitive effects between large gases of CH 4 and N 2 with small helium. [ABSTRACT FROM AUTHOR]

Recently, the intensified vibratory milling (IVM) has emerged as a viable milling technology known for its nanosizing and high-throughput potential. The extent of the heat generation is ambiguously discussed within the literature. For this reason, the impact of formulation and process parameters for both particle size reduction and heat generation, needs further investigation to develop robust processes using the IVM technology. For this reason, the impact on particle size and heat generation of three different process parameters: – bead-suspension ratio; milling time; and acceleration – as well as one formulation parameter – API concentration – was investigated by a one-variable-at-a-time approach. Further the effect of additional fixtures on the heat generation was noted. The data obtained in this work showed that if the impact on heat generation was taken into account, the process parameters could be fine-tuned to optimize the nano-sizing potential while containing a continuous milling process. A longer milling time and production of highly concentrated formulations were proposed as gentle optimisation steps for the herein presented comminution process. [ABSTRACT FROM AUTHOR]

• The effects of rice straw (RS) particle size on biogas production were investigated. • Particle size reduction of the RS significantly enhanced the methane production. • Cellulose degradation contributed to the elevated anaerobic digestion efficiency. • Changes in the RS properties were obtained through the comminution pretreatment. • Particle size reduction decreased the bacterial diversity in digestion system. The objective of this study was to investigate the effects of particle size reduction (20, 1, 0.15, and 0.075 mm) on biogas production from rice straw waste through batch anaerobic digestion experiments. To clarify the digestion mechanisms, the microbial community and rice straw properties including fractal dimension, dissolution abilities and the bio-liquefaction degree were determined. Particle size reduction of rice straw improved methane yield from 107 mL g−1 VS to 197 mL g−1 VS. The elevated digestion efficiency was attributed to the cellulose degradation (degradation rate from 27% to 93%) rather than hemicellulose or lignin. The comminution pretreatment improved the basic morphology, dissolution abilities and bio-liquefaction degree, which associated with the shifts in the bacterial community and the decreased bacterial diversity. These results suggested that particle size reduction of the rice straw in conjunction with optimized microbial growth could improve the methane yield in anaerobic digestion processes. [ABSTRACT FROM AUTHOR]