Significant Reduction In Particle Size Research Articles

Stealth Amphotericin B nanoparticles for oral drug delivery: In vitro optimization

PurposeAmphotericin B (AmB) is an effective anti-fungal and anti-leishmanial agent. However, AmB has low oral bioavailability (0.3%) and adverse effects (e.g., nephrotoxicity). The objectives of this study were to improve the oral bioavailability by entrapping AmB in pegylated (PEG) poly lactide co glycolide copolymer (PLGA–PEG) nanoparticles (NPs). The feasibility of different surfactants and stabilizers on the mean particle size (MPS) and entrapment efficiency were also investigated. Materials and methodsNPs of AmB were prepared by a modified emulsification diffusion method employing a vitamin E derivative as a stabilizer. Physicochemical properties and particle size characterization were evaluated using Fourier Transform Infra-Red spectroscopy (FTIR), differential scanning calorimetry, scanning electron microscopy and transmission electron microscopy. Moreover, in vitro dissolution profiles were performed for all formulated AmB NPs. ResultsMPS of the prepared spherical particles of AmB ranged from 26.4±2.9 to 1068±489.8nm. An increased stirring rate favored AmB NPs with a smaller MPS. There was a significant reduction in MPS, drug content and drug release, when AmB NPs were prepared using the diblock polymer PLGA–PEG with 15% PEG. Addition of three emulsifying agents poly vinyl pyrrolidone (PVP), Vitamin E (TPGS) and pluronic F-68 to AmB formulations led to a significant reduction in particle size and increase in drug entrapment efficiency (DEE) compared to addition of PVP alone. FTIR spectroscopy demonstrated a successful loading of AmB to pegylated PLGA–PEG copolymers. PLGA–PEG copolymer entrapment efficiency of AmB was increased up to 56.7%, with 92.7% drug yield. After a slow initial release, between 20% and 54% of AmB was released in vitro within 24h phosphate buffer containing 2% sodium deoxycholate and were best fit Korsmeyer–Peppas model. In conclusion, PLGA–PEG diblock copolymer with 15% PEG produced a significant reduction (>70%) in MPS with highest drug content. The percentage of PEG in the copolymer and the surfactant/stabilizer used had a direct effect on AmB release in vitro, entrapment efficiency and MPS. These developed formulations are feasible, effective and improved alternatives to other carriers for oral delivery of AmB.

Effect of high pressure homogenisation and heat treatment on physical properties and stability of almond and hazelnut milks

The effect of high pressure homogenisation (HPH) and heat treatments on physicochemical properties and physical stability of almond and hazelnut milks was studied. Vegetable milks were obtained and homogenised by applying 62, 103 and 172 MPa (MF1, MF2 and MF3, respectively). Untreated and MF3 samples were also submitted to two different heat treatments (85 °C/30 min (LH) or 121 °C/15 min (HH)). Physical and structural properties of the products were greatly affected by heat treatments and HPH. In almond milk, homogenised samples showed a significant reduction in particle size, which turned from bimodal and polydisperse to monodisperse distributions. Particle surface charge, clarity and Whiteness Index were increased and physical stability of samples was improved, without affecting either viscosity or protein stability. Hazelnut beverages showed similar trends, but HPH notably increased their viscosity while change their rheological behaviour, which suggested changes in protein conformation. HH treatments caused an increment of particle size due to the formation oil droplet-protein body clusters, associated with protein denaturation. Samples submitted to the combined treatment MF3 and LH showed the greatest stability.

Confined crystallization of drug in directionally freeze-dried water-soluble template

The applicability of confined crystallization is limited by the use of extra template materials unsuitable for oral dosage forms. In consideration of this limitation, mannitol was processed into a template with well controlled pores. This template was used for the subsequent confined crystallization of a model drug, resulting in drug/mannitol composite powders processable into the common operations of oral solid dosage forms. The confined crystallization produced a significant melting point depression, caused by a significant particle size reduction, but did not alter the crystal polymorphism. The in vitro release of drug was significantly improved by the confined crystallization.

Enhanced Delivery of Quercetin by Encapsulation in Poloxamers by Supercritical Antisolvent Process

The promising applications of quercetin as a functional additive in food and pharmaceutical products are hindered by the low bioavailability of this compound. The formulation of quercetin by encapsulation in a surfactant polymer capable of forming micelles in aqueous media can help improve the dissolution of quercetin in water and thus facilitate the assimilation of this compound by organisms. In this work, quercetin was encapsulated in Pluronic F127 poloxamers by the supercritical antisolvent (SAS) technique. The structure and morphology of the product were characterized by SEM, DSC, XRD, and FTIR spectroscopy. The results indicated that, through SAS processing, a significant reduction in particle size was achieved. With appropriate polymer/active compound mass ratios, quercetin was homogeneously dispersed in an amorphous polymer matrix, and no segregated crystalline particles of quercetin were observed. These structural and morphological variations enabled an improved dissolution behavior of quercetin in simulated gastric and intestinal fluids.

Enhancing methane production from rice straw by extrusion pretreatment

Extrusion pretreatment was applied to enhance fermentative methane production from rice straw. The extrusion-pretreated rice straw (EPRS) showed significant particle size reduction, physical properties improvement and volume expansion, as compared to the milling-pretreatment rice straw (MPRS) and unpretreated rice straw (UPRS). The anaerobic digestion of EPRS, MPRS and UPRS with different inoculum-to-substrate ratios (ISRs) and solid loading rates (SLRs) was investigated. The highest specific methane production (SMP) of the EPRS was 227.3L/g VS with an ISR of 0.4 and SLR of 50kg/m3, which was 32.5% and 72.2% greater than that of the MPRS and UPRS at the corresponding ISR and SLR, respectively. Furthermore, the volumetric methane production (VMP) increased with increasing SLR. The highest VMP (17.0m3/m3) of the EPRS was obtained with an SLR of 90kg/m3, which was 1.5 times that of the MPRS. In addition, the EPRS had significantly shorter technical digestion time and higher cellulose and hemicellulose degradation efficiencies, which was due to the smaller particle size and larger specific surface area of the EPRS, thus contributing to the enhancement of methane production. The SEM analyses further demonstrated that the cellulose of the rice straw was devillicated after extrusion pretreatment, which was in agreement with the higher cellulose and hemicellulose degradation efficiencies of the EPRS.

Influence of different dry milling processes on the properties of an attapulgite clay, contribution of inverse gas chromatography

The effect of dry milling processes on the surface properties of an attapulgite clay, also called palygorskite, was investigated by carrying out experiments with different types of grinding devices. Ground products were then characterized by size measurement, scanning electron microscopy, X-ray diffraction, adsorption–desorption of N2 and inverse gas chromatography at infinite dilution (IGC-ID) as well as finite concentration conditions (IGC-FC). These analyses were performed to evaluate the changes in particle size distribution, morphology, crystallinity and surface properties of attapulgite powder, respectively. Among the tested dry grinding devices, grinding in an air jet mill (Alpine 50 AS) and a vibratory ball mill (Pulverisette 0) led to the most significant particle size reduction. SEM photomicrographs showed that a breakage of the fibrous structure took place during dry grinding. Moreover, long grinding in Pulverisette 0 resulted in the complete destruction of fibre morphology followed by agglomeration. XRD analysis showed that whatever the grinding process, the microstructure of the attapulgite was not affected. IGC confirmed that only grinding in Pulverisette 0 affected the surface properties notably. In this case, the most significant decreases were observed in the dispersive component of the surface energy (164 to 116mJ/m2) and in the specific surface area obtained with the octane probe (114.5m2/g to 62.6m2/g) by IGC-ID and IGC-FC, respectively. At the same time, a modification of the distribution functions of the adsorption energies (DFAE), giving information about surface heterogeneity, was noticed.

Flux Behavior and Quality of Effluent from a Poultry Processing Plant Treated by Membrane Bioreactor

Abstract Membrane bioreactor (MBR) provided with spiral wound modules of polyacrylonitrile ultrafiltration membranes was used to treat the wastewater obtained from primary and secondary processing operations of a poultry plant. The membrane bioreactor consisted of 3 tanks; an aerobic bioreactor, anoxic settling tank, and a third tank from which a permeate was drawn across ultrafiltration membranes for final discharge to a municipal sewer or for reuse in the processing of raw product. The Cleaning and backflush schedules were conducted to determine the best regimen for maximum permeate flux and for their effect on retention times in each of the biological treatment tanks. Continuous operation of MBR for 24 h period with no backflushing resulted in flux decay that led to a substantial change in retention times. The best operating cycle was found to be 1 h filtration followed by 120 s backflush or 20 min filtration followed by 20 s backflush. Significant reduction in particle size, COD and BOD (>90%) and reduction of microbial load by 4 – log levels in MBR effluent made it fit for reuse.

Milling of magnesium powders without additives

Abstract Mechanical milling of ductile metals and alloys into fine powders is difficult to achieve due to particle agglomeration. Even though cryogenic milling and/or wet milling can lead to substantial reduction of particle size, the production of fine powders from ductile metals and alloys is a difficult process. The current study deals with the milling of Mg and examines alternative processing methods that would yield an efficient size reduction. Two methods were studied; milling with MgH 2 addition, and milling the powders pre-deformed by equal channel angular pressing (ECAP). The study showed that both methods are successful in preventing particle agglomeration resulting in a significant reduction in particle size. Equal channel angular pressing has the advantage that could be applied to all metals and alloys whereas milling with hydride could only be applied to metals forming their own hydride. It is concluded that, of the two methods, milling with hydride addition is a more effective method of size reduction.

Heat stability of micellar casein concentrates as affected by temperature and pH

The increased interest in using micellar casein concentrates (MCC) obtained by microfiltration in the manufacture of shelf-stable high-protein beverages creates a need to understand the effect of sterilization treatments on the stability of this ingredient. The goals of this work were to (1) elucidate the effects of pH and heat treatment temperatures in the sterilization range on the stability of MCC, and (2) use the generated knowledge to develop solutions for stabilizing the MCC during sterilization treatments. Micellar casein concentrate powders were reconstituted, and the resulting casein dispersions were adjusted to pH values of 6.5 to 7.3. Subsequently, the MCC samples were heated in an oil bath to 110 to 150°C. The treated samples were evaluated for particle size, soluble minerals, and casein dissociation. At pH <6.7, all heat-treated samples were visibly aggregated or coagulated. At pH 6.9, higher temperatures led to increased particle size, whereas at pH >6.9, few or no changes were observed after heat treatment. Casein dissociation increased with increasing pH for all caseins, at all temperatures, with dissociation of κ-casein and β-casein being the most pronounced. At higher pH, the levels of dissociated αs-casein decreased after heat treatment, suggesting aggregation of αs-casein in the presence of Ca and protection lost by κ-casein. It was concluded that increased stability of MCC requires increasing the pH or lowering the processing temperature. After applying these modifications, MCC was submitted to both retorting and UHT sterilization, at equivalent lethality. A significant reduction in particle size was obtained and no coagulation or aggregation occurred after retorting or UHT under the modified conditions as compared with the controls. The knowledge generated in this study will allow the effective stabilization of MCC in practical applications, such as the production of high-protein, shelf-stable beverages.

Influence of High Energy Milling on the Airflow Sensorproperty of the NBCa Ceramic

Some materials have been applied in many surrounding conditions as sensors, electronic devices and other applications. Inexpensive and reliable temperature and flow measurement are important in many applications including, for example, environmental monitoring and control, indoor air conditioning, weather forecasting, automotive and aerospace systems. Special ceramics are an example of such materials. Neodymium-Barium-Copper is a special ceramic that has high electrical conductivity and airflow sensor characteristics. This property is influenced by high energy milling of the powder, when it is not sintered. To evaluate the influence of this type of milling it was carried out an analysis of particle size as a function of milling time. SEM images and granulometric analysis showed significant reduction of particle size with the increase of milling time. For longer times of milling the mixture of precursor powders is favored, resulting in better homogeneity of the ceramic. This is reflected in the properties of airflow sensor.

Ultrasound-intensified mineral carbonation

Several aspects of ultrasound-assisted mineral carbonation were investigated in this work. The objectives were to intensify the CO2 sequestration process to improve reaction kinetics and maximal conversion. Stainless steel slags, derived from the Argon Oxygen Decarburization (AOD) and Continuous Casting/Ladle Metallurgy (CC/LM) refining steps, were used for assessing the technical feasibility of this concept, as they are potential carbon sinks and can benefit from reduction in alkalinity (pH) by mineral carbonation. Ultrasound was applied by use of an ultrasound horn into the reaction slurry, where mineral carbonation reaction took place at 50 °C for up to 4 h; comparison was made to solely mechanically mixed process. It was found that sonication increases the reaction rate after the initial stage, and permits achieving higher carbonate conversion and lower pH. AOD slag conversion increased from 30% to 49%, and pH decreased from 10.6 to 10.1; CC slag conversion increased from 61% to 73% and pH decreased from 10.8 to 9.9. The enhancement effect of ultrasound was attributed to the removal of passivating layers (precipitated calcium carbonate and depleted silica) that surround the unreacted particle core and inhibit mass transfer. Significant particle size reduction was observed for sonicated powders, compared to particle size growth in the case of stirring-only; D[4,3] values increased without sonication by 74% and 50%, and decreased with sonication by 64% and 52%, respectively for AOD and CC slags. Considerations on scale-up of this technology, particularly with regards to energy efficiency, are also discussed.

Benznidazole microcrystal preparation by solvent change precipitation and in vivo evaluation in the treatment of Chagas disease

Benznidazole (BNZ) is traditionally used to treat Chagas disease. Despite its common use, BNZ has a poor water solubility and a variable bioavailability. The purpose of this study was to prepare BNZ microcrystals by solvent change precipitation and to study the effects of BNZ micronisation on therapeutic efficiency using a murine model of Chagas disease. The solvent change precipitation procedure was optimised in order to obtain stable and homogeneous particles with a small particle size, high yield and fast dissolution rate. The thermal and crystallographic analysis showed no polymorphic change in the microcrystals, and microscopy confirmed a significant reduction in particle size. A marked improvement in the drug dissolution rate was observed for micronised BNZ particles and BNZ tablets in comparison with untreated BNZ and commercial Rochagan®. In vivo studies showed a significant increase in the therapeutic efficacy of the BNZ microparticles, corroborating the dissolution results.

Rational design, fabrication, characterization and in vitro testing of biodegradable microparticles that generate targeted and sustained transgene expression in HepG2 liver cells

Poly(lactide-co-glycolide) (PLGA) microparticles have significant potential for sustained delivery of plasmid DNA (pDNA). However, unmodified PLGA microparticles have poor transfection efficiencies. In this study, we use several approaches to enhance the transfection efficiencies of PLGA microparticles in a HepG2 liver cell line. Polyethylenimine (PEI) is used to condense the pDNA prior to loading into the PLGA microparticles. This provides enhanced loading efficiencies and greater protection to the pDNA during the entrapment process. In addition, the pDNA used (ApoE) incorporates a hybrid liver-specific murine albumin enhancer/α1 antitrypsin promoter (AlbE/hAAT) to enhance transgene expression in human liver (HepG2) cells. The percentage of surfactant used in the preparation of the microparticles, the polymer composition of the PLGA, the ratio of the PEI to pDNA (N/P), the structure of the PEI and the potential utility of a galactose targeting ligand were then investigated to further optimize the efficacy of the cationic microparticle non-viral delivery system in transfecting HepG2 cells. For each PLGA PEI-pDNA microparticle formulation prepared, we evaluated particle size, ζ-potential, loading of pDNA, cytotoxicity, and transgene expression in HepG2 cells and control human embryonic kidney (HEK293) and monkey African green kidney fibroblast-like (COS7) cells. Loading PLGA particles with PEI-ApoE pDNA complexes resulted in a significant reduction in particle size when compared to PLGA microparticles loaded with ApoE pDNA alone. Scanning electron microscopy images showed that all the particle formulations were smooth and spherical in appearance. Incorporation of the cationic PEI in the PLGA particles changed the ζ-potential from negative to positive. Complexing PEI with ApoE pDNA increased the loading efficiency of the ApoE pDNA into the PLGA microparticles. The cytotoxicity of PLGA particles loaded with PEI-ApoE pDNA complexes was similar to PLGA particles loaded with ApoE pDNA alone. The transfection efficiency of all particle formulations prepared with ApoE pDNA was significantly higher in HepG2 cells when compared to HEK293 and COS7 cell lines. The release of PEI-pDNA complexes from particles prepared with different PLGA polymer compositions including PLGA 50–50, PLGA 75–25, and PLGA 85–15 was sustained in all cases but the release profile was dependent on the polymer composition. Transmission electron microscopy images showed that PEI-pDNA complexes remained structurally intact after release. The optimum formulation for PLGA particles loaded with PEI-ApoE pDNA complexes was prepared using 2% polyvinyl alcohol, 50–50 PLGA compositions and N/P ratios of 5–10. Strong sustained transgene expression in HepG2 cells was generated by PLGA PEI-ApoE pDNA particles up to the full 13 days tested.

Recrystallization of erlotinib hydrochloride and fulvestrant using supercritical antisolvent process

Recrystallization of two anti-cancer active pharmaceutical ingredients (APIs), erlotinib hydrochloride (erlotinib HCl) and fulvestrant, using supercritical antisolvent (SAS) process was investigated in this study. The most commonly used supercritical carbon dioxide was employed as the antisolvent. Effect of three process parameters including the operating temperature, pressure and solution flow rate have been studied. Analyses of the recrystallized erlotinib HCl and fulvestrant were examined by SEM, XRD and DSC. Erlotinib HCl was recrystallized from its mean particle size of 20 μm to 2 μm with different crystal habits. Different polymorphs of erlotinib HCl were obtained and confirmed from the XRD and DSC results. The prior art polymorph form A of erlotinib HCl showed enhanced dissolution rate by 3.6 times to its original polymorph form B. Significant particle size reduction was also obtained for fulvestrant. The mean particle size was reduced from its original value of 22 μm to 2 μm with much narrower particle size distribution. The cross-interaction effect between the operating temperature and pressure observed in the SAS treatment of fulvestrant was verified by the method of calculated mixture critical point (MCP). The micronized fulvestrant particles showed consistent polymorph as the original API, but with different crystal habits. It is confirmed that the SAS method is applicable for controlling the crystal properties of two APIs, erlotinib HCl and fulvestrant, which require rigorous control of physical characteristics.

Study of a Layered Iron(III) Phosphate Phase Na3Fe3 ( PO4 ) 4 Used as Positive Electrode in Lithium Batteries

The layered phase prepared by solid-state reaction was studied as positive electrode in lithium batteries. Up to 1.9 ions/f.u. could be intercalated, and only 1.7 ions could be extracted between 4.5 and 2 V vs with an average voltage of around . In situ and ex situ X-ray diffraction data and Mössbauer spectroscopy measurements indicate that the intercalation/deintercalation process occurs through a solid solution process and is reversible. To improve its electrochemical performances, was also prepared via a hydrothermal method that leads to a significant particle size reduction. However, no clear improvements of the cycling performances were observed using this material as positive electrode in sodium and lithium batteries.

One-step compatibilization of polyamide 6/ poly (ethylene-1-octene) blends with maleic anhydride and peroxide

Polyamide 6/poly(ethylene-1-octene) (POE) blends were prepared in the presence of both maleic anhydride and peroxide via melt blending. The intrinsic viscosity, mechanical properties, rheology, and phase morphology of blends were evaluated. Molau test was adopted to confirm the formation of a graft copolymer between PA 6 and POE, rheology property also indicated the graft reaction. The SEM analysis showed a significant reduction in particle size of seperation phase after one-step compatibilization. It provides a promising method to obtain toughened polyamide material.

Effectiveness of dust dispersion in the 20-L Siwek chamber

The Siwek 20-L chamber is widely used throughout the world to evaluate the explosibility of dusts. This research evaluated the quality of dust dispersion in the Siwek 20-L chamber using Pittsburgh coal, Gilsonite, and purple K dusts. A Pittsburgh Research Laboratory (PRL) optical dust probe was used to measure optical transmittance through the dust cloud at various locations within the chamber. A total of 540 tests were performed, with triplicate tests at five nominal dust concentrations and six locations. The two standard dispersion nozzles (rebound and perforated annular nozzle) were compared. The transmissions corresponding to the normal ignition delay period were used to: (a) determine variations in spatial uniformity of dispersion obtained with both nozzles; (b) make comparisons between the experimental transmission data and those calculated from theory for the three dusts; and (c) make comparisons with transmission data measured in the PRL 20-L and Fike 1-m 3 dust explosion chambers. The uniformity of dispersion for the three dusts was similar with both nozzles, despite the differences in nozzle geometry and mode of operation. Transmission data of the three dusts were all significantly lower than those calculated from theory. This was discovered to be, in part, due to significant reduction in particle size that occurred during dispersion. By measuring particle sizes before and after dispersion, values of 60%, 50%, and 20% reduction in particle size (based on the surface-weighted mean diameter) were obtained for Pittsburgh coal, Gilsonite, and purple K, respectively. Transmission data from the PRL 20-L, Fike 1-m 3 and the Siwek 20-L chambers indicated comparable results in terms of uniformity of dispersion. However, transmission data from the Siwek 20-L chamber were significantly lower than those of the PRL and Fike chambers. Again, this was attributed, in part, to the significant reduction in particle size that occurred during dispersion in the Siwek chamber. The design of the outlet (dispersion) valve of the Siwek 20-L apparatus charge vessel was largely responsible for the particle break-up. The contribution to particle break-up by the dispersion nozzles and the high level of turbulence in the chamber were found to be minimal. This is a significant finding in that the dust particle size tested for explosibility in the Siwek chamber is considerably smaller than the original dust sample.

Fabrication and characterization of eco-friendly functional wallpaper using nonmetallic minerals

The effects of amounts and particle size of nonmetallic minerals on the rheological behavior of the slurry and microstructure evolution of an eco-friendly functional wallpaper were investigated to optimize preparation parameters. Mixed binder system was used to prepare the wallpaper. Nonmetallic minerals such as TiO 2, CaCO 3, illite, pearl, and small amounts of graphite were mixed with the binder and then ball milled for 12 h. The particle size of the starting materials was controlled by the milling process, showing a significant reduction in particle size. Mixed slurries coated on base paper (substrate) were dried and pressed at 150 °C, forming seven layers. The reduced particle size increases the amounts of the nonmetallic minerals in the slurry, which causes an increase in viscosity and inhibits powder sedimentation. Despite the increase in the amounts of nonmetallic minerals, the nonmetallic minerals are homogeneously dispersed, as confirmed by microstructure and EDS mapping. The nonmetallic minerals provide the wallpaper with eco-friendly functions such as unit-infrared emission and antifungal ability, and improve the deodorization ratio and decrease the emission ratio of TVOC and HCHO compared with conventional wallpaper.

Synthesis and structural characterization of uranium-doped Ca2CuO3, a one-dimensional quantum antiferromagnet

The technological settings of a modified sol-gel method for the preparation of highly fine homogeneous powder of Ca2CuO3 doped with uranium 238 (x= 0.0–0.05) is presented. The analysis of structure, purity of phases and the justification for the role of uranium in the given compounds are provided, together with an almost complete classification of the observed optical phonons by means of Raman, IR measurements and ab initio calculations. A significant reduction in particle size was achieved by doping, and a strong correlation between resistivity and doping concentration was observed and explained using the phonon-assisted electron hopping conduction model. The persistence of a covalent insulation state in all compounds is an interesting feature of this doping.

A comparative study of approaches used to improve solubility of roxithromycin

Roxithromycin (ROX), a class IV drug has 50% absolute oral bioavailability due to poor aqueous solubility. The present study deals with exploring the effect of homogenization, homogenization followed by freeze drying and homogenization followed by spray drying in the presence of solubilizers on drug solubility and dissolution rate. Homogenization and subsequent freeze drying resulted in 3–4 fold increase in saturation solubility and 18 times faster dissolution as compared to the pure drug. In this study, a more preferred aqueous system was developed for enhancement of the saturation solubility and dissolution rate and compared with the non-aqueous system. Interestingly the aqueous system was found equally effective and comparatively more stable. Enhancement of the saturation solubility and dissolution rate was a result of significant particle size reduction, improved hydrophilicity and complete or partial transformation to amorphous form as evidenced by DSC and XRPD studies. The study focused on utilization of solubilizer to synergistically enhance the efficiency of the processing techniques. The effect of processing and formulation variables on the saturation solubility, in vitro dissolution, drug crystallinity, physical interaction, antimicrobial activity and stability was also monitored.