Quantitative Characterization of Agglomerate Abrasion in a Tumbling Blender by Using the Stokes Number Approach

Removal of microcrystalline cellulose agglomerates in a dry-mixing system (lactose, 100 M) predominantly occurs via abrasion. The agglomerate abrasion rate potential is estimated by the Stokes abrasion (St_Abr) number of the system. The St_Abr number equals the ratio between the kinetic energy density of the moving powder bed and the work of fracture of the agglomerate. Basically, the St_Abr number concept describes the blending condition of the dry-mixing system. The concept has been applied to investigate the relevance of process parameters on agglomerate abrasion in tumbling blenders. Here, process parameters such as blender rotational speed and relative fill volumes were investigated. In this study, the St_Abr approach revealed a transition point between abrasion rate behaviors. Below this transition point, a blending condition exists where agglomerate abrasion is dominated by the kinetic energy density of the powder blend. Above this transition point, a blending condition exists where agglomerates show (undesirable) slow abrasion rates. In this situation, the blending condition is mainly determined by the high fill volume of the filler.     

Agglomerates Containing Pantoprazole Microparticles: Modulating the Drug Release

Pantoprazole-loaded microparticles were prepared using a blend of Eudragit® S100 and Methocel® F4M. The accelerated stability was carried out during 6 months at 40°C and 75% relative humidity. In order to improve technological characteristics of the pantoprazole-loaded microparticles, soft agglomerates were prepared viewing an oral delayed release and gastro-resistant solid dosage form. The agglomeration was performed by mixing the pantoprazole microparticles with spray-dried mannitol/lecithin powders. The effects of factors such as the amount of lecithin in the spray-dried mannitol/lecithin powders and the ratio between pantoprazole microparticles and spray-dried mannitol/lecithin powders were evaluated. The pantoprazole-loaded microparticles present no significant degradation in 6 months. The agglomerates presented spherical shape, with smooth surface and very small quantity of non-agglomerated particles. The agglomerates presented different yields (35.5–79.0%), drug loading (58–101%), and mechanical properties (tensile strength varied from 44 to 69 mN mm⁻²), when the spray-dried mannitol/lecithin powders with different lecithin amounts were used. The biopharmaceutical characteristics of pantoprazole microparticles, i.e., their delayed-release properties, were not affected by the agglomeration process. The gastro-resistance of the agglomerates was affected by the amount of spray-dried mannitol/lecithin powders. The ratio of lecithin in the spray-dried mannitol/lecithin powders was the key factor in the agglomerate formation and in the drug release profiles. The agglomerates presenting better mechanical and biopharmaceutical characteristics were prepared with 1:2 (w/w) ratio of pantoprazole-loaded microparticles and mannitol/lecithin (80:20) powder.Key words: agglomerates, delayed release, gastro-resistance, microparticles     

Trace metals in large agglomerates (marine snow)

Marine agglomerates were collected by SCUBA from surface watersof Monterey Bay, California and one coastal site 100 km offPoint Sur, California using trace metal clean techniques. Concentrationsof Al, Fe, Mn, Cu, Ni, Zn, Cd and Pb were measured for bothweak acid soluble and refractory metals and compared to suspendmaterial collected in water bottles at the same locations. Gravimetricanalysis of agglomerate and surrounding suspended particulatematter indicated that although agglomerates represented <0.1%of total water sample volume (determined photographically),they contained up to 50% of the total particulate dry weight;trace metal concentrations in the agglomerate fraction werealso disproportionately high. Agglomerates collected withinMonterey Bay contained large quantitites of inorganic material(>40% dry weight), with most of the associated metals containedprimarily within the refractory fraction. In contrast, the offshorestation agglomerates contained <0.3% inorganic material withmetals primarily associated with the weak acid soluble fraction.Both the metal concentrations and leach characteristics of theoffshore station suggest that these agglomerates were comprisedof an active phytoplankton assemblage highly enriched in Cd.Metal concentrations in the offshore samples in conjunctionwith agglomerate abundance indicate that agglomerates may bea major transporter of trace metals out of the euphotic zone.     

Effect of Surface Coating with Magnesium Stearate via Mechanical Dry Powder Coating Approach on the Aerosol Performance of Micronized Drug Powders from Dry Powder Inhalers

The objective of this study was to investigate the effect of particle surface coating with magnesium stearate on the aerosolization of dry powder inhaler formulations. Micronized salbutamol sulphate as a model drug was dry coated with magnesium stearate using a mechanofusion technique. The coating quality was characterized by X-ray photoelectron spectroscopy. Powder bulk and flow properties were assessed by bulk densities and shear cell measurements. The aerosol performance was studied by laser diffraction and supported by a twin-stage impinger. High degrees of coating coverage were achieved after mechanofusion, as measured by X-ray photoelectron spectroscopy. Concomitant significant increases occurred in powder bulk densities and in aerosol performance after coating. The apparent optimum performance corresponded with using 2% w/w magnesium stearate. In contrast, traditional blending resulted in no significant changes in either bulk or aerosolization behaviour compared to the untreated sample. It is believed that conventional low-shear blending provides insufficient energy levels to expose host micronized particle surfaces from agglomerates and to distribute guest coating material effectively for coating. A simple ultra-high-shear mechanical dry powder coating step was shown as highly effective in producing ultra-thin coatings on micronized powders and to substantially improve the powder aerosolization efficiency.     

Transformed roots of Artemisia annua exhibit an unusual pattern of border cell release

Summary Border cells from Artemisia annua were examined from hairy roots grown in shake flasks, culture plates, a bubble column reactor, and a nutrient mist (aeroponic) reactor. When well-hydrated roots were subjected to shear, border cells were first released as an agglomerate and did not disperse for several hours. Staining with neutral red and fluorescein diacetate (FDA) showed that both agglomerates and dispersed cells were alive. It was determined that FDA is cleaved by pectin methylesterase (PME) and that PME may not be particularly active in the released agglomerates until the border cells disperse. Untransformed roots isolated from A. annua plants showed no border cell agglomerate formation and border cells readily dispersed. These results suggest that our hairy root clone is deficient in border cell release perhaps resulting from the transformation process.     

Influence of bulk and tapped density on the determination of the thermal conductivity of powders and blends

The aim of this study was to evaluate a non-steady-state needle sensor to determine the thermal conductivity (lambda) of powders and their blends. It was investigated how lambda of different powders was influenced by (1) bulk vs tapped density, (2) moisture content of the powders, and (3) blending time of the powders. Different powders were evaluated: 2 lactose powders with different properties, a microcrystalline cellulose powder, a cornstarch powder, and 3 herbal extracts. The results show that the values of lambda are highly dependent on the bulk and tapped density of the powders. Bulk density measurements were generally not sensitive enough to detect the moisture content within a powder. The tapped density measurements were reliable and highly reproducible and could differentiate between the nature of a powder and the powder moisture content. Measurements of lambda were able to be used to monitor the powder blending process. To be able to use thermal conductivity measurements to characterize powder properties in quality control, the powder density must be defined because changes in density affect lambda. Using thermal conductivity as a measure for process analytical technology seems to be feasible and can add valuable information to the process under investigation.     

Structural changes in the transition state of protein folding: alternative interpretations of curved chevron plots.

The interpretation of folding rates is often rationalized within the context of transition state theory. This means that the reaction rate is linked to an activation barrier, the height of which is determined by the free energy difference between a ground state (the starting point) and an apparent transition state. Changes in the folding kinetics are thus caused by effects on either the ground state, the transition state, or both. However, structural changes of the transition state are rarely discussed in connection with experimental data, and kinetic anomalies are commonly ascribed to ground state effects alone, e.g., depletion or accumulation of structural intermediates upon addition of denaturant. In this study, we present kinetic data which are best described by transition state changes. We also show that ground state effects and transition state effects are in general difficult to distinguish kinetically. The analysis is based on the structurally homologous proteins U1A and S6. Both proteins display two-state behavior, but there is a marked difference in their kinetics. S6 exhibits a classical V-shaped chevron plot (log observed rate constant vs denaturant concentration), whereas U1A's chevron plot is symmetrically curved, like an inverted bell curve. However, S6 is readily mutated to display U1A-like kinetics. The seemingly drastic effects of these mutations are readily ascribed to transition state movements where large kinetic differences result from relatively small alterations of a common free energy profile and broad activation barriers.     

The Cytokines Responses against Parvovirus B19 in Miscarriage Women and the Susceptibility of their RhD Blood Type to Contract Parvovirus B19 in South of Iraq

Background:Parvovirus B19 (B19) infection is linked with various diseases. Cytokines play critical roles in cellular response to viral infection. It has also been reported that’s susceptibility of the ABO blood type people to several viral infection. In this study, we evaluated interleukin 6 (IL-6), interleukin 8(IL-8), and interferon gamma (IFN-γ) levels in aborted women infected with parvovirus B19 (B19+/Abr+) and uninfected with B19(B19-/Abr+) in comparison with healthy women (B12-/Abr-) and susceptibility of their RhD blood type to contract B19.Methods:B19+/Abr+ were diagnosed using IgM and IgG antibodies against B19, and the concentrations of IL-6, IL-8, and IFN-γ were determined using enzyme-linked immunosorbent assay (ELISA) test in both B19+/Abr+, B19-/Abr+, and B19-/Abr-. Here, we also collected blood groups, number of abortion, and gestational ages from 200 B19+/Abr+ along with the same number ofB19-/Abr+ and B19-/Abr-.Results:The levels of IFN-γ were higher in serum of B19-/Abr+andB19+/Abr+ group in comparison to B19-/Abr-, while the serum levels of IL-6, IL-8were increased in B19+/Abr+ group in comparisontoB19-/Abr+ and B19-/Abr-. Our analyzed data also showed that aborted women with RhD+ are more susceptible to contract s B19 than people with RhD- blood type.Conclusion:B19 infection may differently modulate the amount of cytokines in the plasma of aborted women. So, it can be suggested that IL-6, IL-8, and IFN-γ potentially useful as markers for inflammation intrauterine. The susceptibility/protection of aborted women against B19 might be determined based on RhD blood type.Key Words: Aborted women, IL-6, IL-8, IFN-γ, Parvovirus B19, RhD blood type     

Study of biodegradable polylactide/poly(butylene adipate-co-terephthalate) blends

Both polylactide (PLA) and poly(butylene adipate-co-terephthalate) (PBAT) are biodegradable polymers. They are thermoplastics which can be processed using most conventional polymer processing methods. PLA is high in strength and modulus (63 MPa and 3.4 GPa, respectively) but brittle (strain at break 3.8%) while PBAT is flexible and tough (strain at break approximately 710%). In view of their complementary properties, blending PLA with PBAT becomes a natural choice to improve PLA properties without compromising its biodegradability. In this study, PLA and PBAT were melt blended using a twin screw extruder. Melt elasticity and viscosity of the blends increased with the concentration of PBAT. Crystallization of the PLA component, phase morphology of the blend, mechanical properties, and toughening mechanism were investigated. The blend comprised an immiscible, two-phase system with the PBAT evenly dispersed in the form of approximately 300 nm domains within the PLA matrix. The PBAT component accelerated the crystallization rate of PLA but had little effect on its final degree of crystallinity. With the increase in PBAT content (5-20 wt %), the blend showed decreased tensile strength and modulus; however, elongation and toughness were dramatically increased. With the addition of PBAT, the failure mode changed from brittle fracture of the neat PLA to ductile fracture of the blend as demonstrated by tensile test and scanning electron microcopy (SEM) micrographs. Debonding between the PLA and PBAT domains induced large plastic deformation in PLA matrix ligaments.     

Plasticity of repetitive DNA in response to metal stress in Bryophytes

Abstract

The relationship between environmental stresses and the genome was investigated by examining the behaviour of repetitive DNA in response to lead or cadmium in two Bryophytes, differing from a physiological and an ecological point of view, namely the aquatic moss L. riparium and the terricolous moss F. hygrometrica. Using different experimental approaches, a direct relationship was shown to exist in these two mosses between the metal-induced stress and repetitive DNA. In fact, in both organisms, metal treatment was accompanied by a selective amplification of some GC-rich repetitive DNA sequences forming peculiar agglomerates inside the nucleus; this amplification is quantitatively proportional to the time of exposure of the plants to the metals and stops upon removal of the metal from the culture medium. Results show that ribosomal DNA sequences are involved in this metal-induced repetitive DNA agglomerate formation, although they are not the only repetitive sequences present within the heterochromatic DNA agglomerates. The plasticity of the genome of the Bryophytes in response to external stimuli, and the fact that repetitive DNA is involved in this plasticity are discussed.     

Challenges in Detecting Magnesium Stearate Distribution in Tablets

Magnesium stearate (MS) is the most commonly used lubricant in pharmaceutical industry. During blending, MS particles form a thin layer on the surfaces of the excipient and drug particles prohibiting the bonding from forming between the particles. This hydrophobic layer decreases the tensile strength of tablets and prevents water from penetrating into the tablet restraining the disintegration and dissolution of the tablets. Although overlubrication of the powder mass during MS blending is a well-known problem, the lubricant distribution in tablets has traditionally been challenging to measure. There is currently no adequate analytical method to investigate this phenomenon. In this study, the distribution of MS in microcrystalline cellulose (MCC) tablets was investigated using three different blending scales. The crushing strength of the tablets was used as a secondary response, as its decrease is known to result from the overlubrication. In addition, coating of the MCC particles by MS in intact tablets was detected using Raman microscopic mapping. MS blending was more efficient in larger scales. Raman imaging was successfully applied to characterize MS distribution in MCC tablets despite low concentration of MS. The Raman method can provide highly valuable visual information about the proceeding of the MS blending process. However, the measuring set-up has to be carefully planned to establish reliable and reproducible results.     

Improvement in ductility of chitosan through blending and copolymerization with PEG: FTIR investigation of molecular interactions

Chitosan is an important biomaterial used widely in medical applications. One of the key concerns about its use is the fragile nature of chitosan films. By comparing the component molecular interactions using FTIR, this study attempts to understand how the ductility of chitosan can be improved by blending and copolymerizing with poly(ethylene glycol) (PEG). An improvement in ductility was obtained for all compositions of blend as manifested by a decrease in modulus and an increase in strain at break. For comparable PEG composition (approximately 30%), the properties of the solution-cast blend were better than those of the grafted copolymer. Therefore, blending may be a more efficient way to improve ductility of chitosan. FTIR characterization of the materials revealed subtle decreases in molecular interactions upon annealing the partially miscible blend. These may not be apparent in DSC or X-ray diffraction, yet they play a key role in the mechanical behavior. It appears that in the case of the graft copolymer the improvement in the properties comes from suppression of the crystallinity of each component and not from component interactions. On the other hand, in the blend, the improvement appears to come predominantly from the "well-dispersed", "kinetically trapped" phase morphology and from the intermolecular interactions. Therefore, annealing the blend leads to decreased intermolecular interactions, phase coarsening, and deterioration in properties.     

A Kinetic Study of the Polymorphic Transformation of Nimodipine and Indomethacin during High Shear Granulation

The objective of the present study was to investigate the mechanism, kinetics, and factors affecting the polymorphic transformation of nimodipine (NMD) and indomethacin (IMC) during high shear granulation. Granules containing active pharmaceutical ingredient, microcrystalline cellulose, and low-substituted hydroxypropylcellulose were prepared with ethanolic hydroxypropylcellulose solution, and the effects of independent process variables including impeller speed and granulating temperature were taken into consideration. Two polymorphs of the model drugs and granules were characterized by X-ray powder diffraction analysis and quantitatively determined by differential scanning calorimetry. A theoretical kinetic method of ten kinetic models was applied to analyze the polymorphic transformation of model drugs. The results obtained revealed that both the transformation of modification I to modification II of NMD and the transformation of the α form to the γ form of IMC followed a two-dimensional nuclei growth mechanism. The activation energy of transformation was calculated to be 7.933 and 56.09 kJ·mol⁻¹ from Arrhenius plot, respectively. Both the granulating temperature and the impeller speed affected the transformation rate of the drugs and, in particular, the high shear stress significantly accelerated the transformation process. By analyzing the growth mechanisms of granules in high-shear mixer, it was concluded that the polymorphic transformation of NMD and IMC took place in accordance with granule growth in a high-shear mixer.     

The formation of strong intermolecular interactions in immiscible blends of poly(vinyl alcohol) (PVA) and lignin

The intermolecular interactions of lignin with a hydrophilic polymer, poly(vinyl alcohol) (PVA), were studied using thermal analyses and FT-IR spectroscopy of a series of PVA/hardwood kraft lignin blend fibers prepared by thermal extrusion. Although two phases are observed in this blend system, some of the lignin was closely associated with the PVA in the PVA-rich phase. The crystallinity of the PVA fraction was reduced with increasing lignin content. An interaction energy density of -9.34 cal cm(-1), calculated from melting point depression data, suggests that strong intermolecular interactions exist between PVA and lignin. FT-IR analysis indicates the formation of strong intermolecular hydrogen bonds between the hydroxyl groups of PVA and lignin. Although the PVA/lignin blend system is immiscible in the bulk, the results herein show the existence of some specific intermolecular interaction between PVA and lignin.     

Preparation and characterization of biodegradable poly-3-hydroxybutyrate-starch blend films

Bacterial polyesters have attracted much attention as biodegradable biocompatible polymers. Poly-3-hydroxybutyrate, a microbially produced thermoplastic, has similar material properties to polypropylene. Its potential application as biodegradable and biocompatible plastics is well documented. However, due to high cost it is used mainly in biomaterials for medical applications. Materials with useful properties may result from blending bacterial polyhydroxybutyrate (PHB) with other polymers. In this paper, the compatibility of PHB with starch for improved properties and cost reduction is discussed. The thermal and mechanical properties of the blended films were studied by means of thermogravimetry, differential scanning calorimetry and an automated material testing system. The results revealed that blend films had a single glass transition temperature for all the proportions of PHB:starch tested. The nature of all combinations was found to be crystalline. The tensile strength was optimum for the PHB:starch ratio of 0.7:0.3 (wt/wt). The variation in tensile strength, Young's modulus, extension needed to break, thermal stability, glass transition temperature, melting temperature, for the different proportions of PHB:starch are discussed.     

Substrate ground state binding energy concentration is realized as transition state stabilization in physiological enzyme catalysis

Previously published kinetic data on the interactions of seventeen different enzymes with their physiological substrates are re-examined in order to understand the connection between ground state binding energy and transition state stabilization of the enzyme-catalyzed reactions. When the substrate ground state binding energies are normalized by the substrate molar volumes, binding of the substrate to the enzyme active site may be thought of as an energy concentration interaction; that is, binding of the substrate ground state brings in a certain concentration of energy. When kinetic data of the enzyme/substrate interactions are analyzed from this point of view, the following relationships are discovered: 1) smaller substrates possess more binding energy concentrations than do larger substrates with the effect dropping off exponentially, 2) larger enzymes (relative to substrate size) bind both the ground and transition states more tightly than smaller enzymes, and 3) high substrate ground state binding energy concentration is associated with greater reaction transition state stabilization. It is proposed that these observations are inconsistent with the conventional (Haldane) view of enzyme catalysis and are better reconciled with the shifting specificity model for enzyme catalysis.     

典型喀斯特森林土壤的抗蚀性

喀斯特地区生态脆弱,极易发生土壤侵蚀。受地表要素空间异质性的影响,目前相关研究仍无法完全反映出喀斯特地区不同植被类型土壤抗蚀性的特征。通过野外调查,了解样地植被群落类型及其组成等基本情况,并以"S形布点法"实地采样;通过酒精烘烤法、环刀法等方法,获取土壤含水量、土壤容重、土壤有机质、土壤团聚体、土壤微团聚体及土壤机械组成、土壤抗蚀指数等土壤抗蚀指标值。结果表明,除有机质外的其他抗蚀指标表现出0—10cm土层内与10—20cm土层内的变化规律均和抗蚀指数一致。在土壤深度0—10cm范围内,土壤抗蚀指数表征的土壤抗蚀能力强弱为:阔叶林灌丛针叶林;在10—20cm土层范围为:灌丛针叶林阔叶林。0—10cm土层内各指标表征土壤抗蚀能力的显著程度为:有机质含量、水稳性团聚体、结构破坏率、团聚状况和团聚度较显著,10—20cm土层内为有机质含量、干筛团聚体、团聚度较为显著,水稳性团聚体次之。通过综合两个土层的情况,可认为有机质含量、水稳性团聚体、团聚度能较好地表征喀斯特林地土壤抗蚀性强弱。在喀斯特地区如果以防治土壤侵蚀为目的,应考虑种植阔叶树种,避免针叶树种。     

Structural characterization and properties of starch/konjac glucomannan blend films

In this work, a series of glycerol-plasticized pea starch/konjac glucomannan (ST/KGM) blend films was prepared by a casting and solvent evaporation method. The structure, thermal behavior, and mechanical properties of the films were investigated by means of Fourier Transform Infrared Spectroscopy, wide-angle X-ray diffraction, scanning electron microscopy, differential scanning calorimetry, and tensile testing. The results indicated that strong hydrogen bonding formed between macromolecules of starch (ST) and konjac glucomannan (KGM), resulting in a good miscibility between ST and KGM in the blends. Compared with the neat ST, the tensile strength of the blend films were enhanced significantly from 7.4 to 68.1 MPa with an increase of KGM content from 0 to 70 wt%. The value of elongation at break of the blend films was higher than that of ST and reached a maximum value of 59.0% when the KGM content was 70 wt% and 20% of glycerol as plasticizer. The incorporation of KGM into the ST matrix also led to an increase of moisture uptake for the ST-based materials. The structure and properties of pea starch-based films were modified and improved by blending with KGM.     

Numerical simulations of ion and electron transport in a low-temperature dusty plasma

Charged particle transport and kinetic processes in a low-temperature dusty plasma are numerically simulated. Dust grains are represented as spheres with a given radius. The self-consistent electric field in the plasma surrounding a charged dust grain is calculated taking into account the perturbations of plasma quasineutrality near the grains. It is shown that applying an external electric field leads to a rearrangement of the plasma space charge and a break of the spherical symmetry of the electron and ion density distributions around the grain. The mutual influence of two identical charged dust grains is considered, and the energy of the electrostatic interaction between the grains is calculated. It is shown that this energy has a minimum at a certain finite distance between the grains.     

The parasitism of the mouldPenicillium purpurogenum onAspergillus niger

The mycelium from a surface culture of the fungusAspergillus niger was mechanically destroyed in a mixer. By this action three distinct particle types arose: isolated hyphae, hyphae agglomerates and granules of cytoplasm. The hyphae agglomerates were removed by fractional centrifugation, the hyphae were separated from the granules by repeated filtration over a sieve with openings 0.063 mm. The isolated hyphae were then deprived of the cytoplasm by the action of pancreatin. Thus obtained cell walls preserved the cell shape and were free of cell contents. The chemical composition of the walls exhibits a dispersion after the mycelium origin. The walls give a positive reaction on chitin, and contain 55 to 85% of the total carbohydrate contents (cellulose 2.5 to 5.5%), 1.5 to 2.1% of total N₂ (0.8 to 0.9% of the amino-N₂) and 8% of the lipides. After an acid hydrolysis, the presence of 45 to 59% of glucose, 9.5 to 14.5% of glucosamine, 1.5 to 6% of galactose, and small amounts of arabinose and mannose were determined. By qualitative chromatography, several aminoacids were ascertained.