In vitro and in vivo studies on the complexes of glipizide with water-soluble β-cyclodextrin-epichlorohydrin polymers

The purpose of this study was to evaluate the potential of a newly modified cyclodextrin derivative, water-soluble β-cyclodextrin-epichlorohydrin polymer (β-CDP), as an effective drug carrier to enhance the dissolution rate and oral bioavailability of glipizide as a poorly water-soluble model drug. Inclusion complexes of glipizide with β-CDP were prepared by the co-evaporation method and characterized by phase solubility, dissolution, and differential scanning calorimetry. The solubility curve was classified as type A(L), which indicated the formation of 1:1 complex between glipizide and β-CDP. β-CDP had better properties of increasing the aqueous solubility of glipizide compared with HP-β-CD. The dissolution rate of drug from the β-CDP complexes was significantly greater than that of the corresponding physical mixtures indicating that the formation of amorphous complex increased the solubility of glipizide. Moreover, the increment in drug dissolution rate from the glipizide/β-CDP systems was higher than that from the corresponding ones with HP-β-CD, which indicated that β-CDP could provide greater capability of solubilization for poorly soluble drugs. Furthermore, in vivo study revealed that the bioavailability of glipizide was significantly improved by glipizide /β-CDP inclusion complex after oral administration to beagle dogs.     

In vitro and in vivo studies on the complexes of glipizide with water-soluble β-cyclodextrin–epichlorohydrin polymers

The purpose of this study was to evaluate the potential of a newly modified cyclodextrin derivative, water-soluble β-cyclodextrin–epichlorohydrin polymer (β-CDP), as an effective drug carrier to enhance the dissolution rate and oral bioavailability of glipizide as a poorly water-soluble model drug. Inclusion complexes of glipizide with β-CDP were prepared by the co-evaporation method and characterized by phase solubility, dissolution, and differential scanning calorimetry. The solubility curve was classified as type A_L, which indicated the formation of 1:1 complex between glipizide and β-CDP. β-CDP had better properties of increasing the aqueous solubility of glipizide compared with HP-β-CD. The dissolution rate of drug from the β-CDP complexes was significantly greater than that of the corresponding physical mixtures indicating that the formation of amorphous complex increased the solubility of glipizide. Moreover, the increment in drug dissolution rate from the glipizide/β-CDP systems was higher than that from the corresponding ones with HP-β-CD, which indicated that β-CDP could provide greater capability of solubilization for poorly soluble drugs. Furthermore, in vivo study revealed that the bioavailability of glipizide was significantly improved by glipizide /β-CDP inclusion complex after oral administration to beagle dogs.     

The effect of shale in quartzite aggregate on the creep and shrinkage of concrete—A comparison with RILEM model B3

This paper presents the results of an investigation into the effects of increasing shale content in nominally “quartzite” aggregates on the creep and shrinkage behaviour of concretes made with such aggregate. The investigation was prompted by concern because of the increasing presence of the weaker and poorly shaped shale particles appearing in the quartzite aggregates being used in the Gauteng region of South Africa. In this investigation, two strength grades of concrete were prepared using varying proportions of shale in the stone and sand fractions of the quartzite aggregates. A secondary outcome of this investigation was the opportunity to assess the effect of aggregate type on the prediction of concrete creep and shrinkage using Model B3. The results indicate that increasing shale content in concrete has a significant effect in increasing both creep and shrinkage strains. Shrinkage increases almost linearly with increasing shale content of the total aggregate. On the other hand, shale in the sand fraction appears to have a larger effect in increasing creep than shale in the stone fraction. An assessment of the need for an aggregate-based adjustment to Model B3 is also presented.

---

Résumé Cet article présente les résultats d’une recherche relative aux effects que peut avoir l’augmentation de la teneur en schiste dans des granulats nominalement “quartzites” sur le comportement des bétons faits avec de tels granulats. La présente recherche est née du souci de comprendre la teneur croissante des particules de schiste plus faibles et mal formées apparaissant dans les granulats quartzites utilisés dans la région de Gauteng en Afrique du sud. Au cours de cette recherche, deux gammes de résistance de béton ont été préparées en utilisant des proportions variables de schiste dans les fractions de pierre et de sable des granulats quartzites. La recherche a aussi été l’occasion d’évaluer les effets du type granulat sur la prévision du fluage et du retrait du béton en utilisant le modèle B3. Les résultats indiquent qu’une augmentation de la teneur de schiste dans du béton a un effet significatif sur l’augmentation des contraintes du fluage et du retrait. Le retrait augmente presque linéairement avec l’augmentation de la teneur en schiste du granulat total. D’autre part, le schiste dans la fraction de sable semble avoir un plus grand effet sur l’augmentation du fluage que le schiste dans la fraction en pierre. Une évaluation du besoin d’un réglage basé sur le granulat par rapport au modèle B3 est également présentée.

---

---

Editorial Note Dr. Yunus Ballim is a RILEM Senior Member.     

The effect of rhBMP-2 and PRP delivery by biodegradable β-tricalcium phosphate scaffolds on new bone formation in a non-through rabbit cranial defect model

This study evaluated whether the combination of biodegradable β-tricalcium phosphate (β-TCP) scaffolds with recombinant human bone morphogenetic protein-2 (rhBMP-2) or platelet-rich plasma (PRP) could accelerate bone formation and increase bone height using a rabbit non-through cranial bone defect model. Four non-through cylindrical bone defects with a diameter of 8-mm were surgically created on the cranium of rabbits. β-TCP scaffolds in the presence and absence of impregnated rhBMP-2 or PRP were placed into the defects. At 8 and 16 weeks after implantation, samples were dissected and fixed for analysis by microcomputed tomography and histology. Only defects with rhBMP-2 impregnated β-TCP scaffolds showed significantly enhanced bone formation compared to non-impregnated β-TCP scaffolds (P < 0.05). Although new bone was higher than adjacent bone at 8 weeks after implantation, vertical bone augmentation was not observed at 16 weeks after implantation, probably due to scaffold resorption occurring concurrently with new bone formation.     

The formation of NaMg2Al15O25 in an α-Al2O3 matrix and its effect on the mechanical properties of alumina

An in-situ sintering reaction was designed to produce lath-like \-alumina in an -alumina matrix in order to make alumina ceramics stronger and tougher. The reaction sequence to produce \-alumina (NaMg₂Al₁₅O₂₅) requires the formation of \-alumina (NaAl₁₁O₁₇) and spinel (MgAl₂O₄) at around 1100 dgC followed by a solid-state reaction of these two phases to give \-alumina at elevated temperatures; this reaction is complete at around 1600 °C. The in-situ sintering reaction produces near-theoretically dense alumina ceramics in which lath-like \-aluminas are homogeneously distributed. The bending strength and fracture toughness increase to 620 MPa and 5 MPam^1/2, respectively; these increases are thought to be due to the suppression of grain growth as well as the crack deflection and bridging associated with lath-like \-alumina.     

Bone response to surface modified titanium implants – studies on the tissue response after 1 year to machined and electropolished implants with different oxide thicknesses

The bone formation around titanium implants with varied surface properties was investigated after 1 year in rabbits. Machined and electropolished samples with and without thick, anodically formed surface oxides were prepared, surface characterized and inserted in the cortical bone of rabbits. Scanning electron microscopy, scanning Auger electron spectroscopy and atomic force microscopy revealed marked differences in oxide thickness, surface topography and roughness, but no significant differences in surface chemical composition between the different groups of implants. Light microscopic morphology and morphometry showed that all implants were in contact with bone and had a large proportion of bone within the threads. There were no significant differences between the differently prepared implant groups. Our study shows that a high degree of bone contact and bone formation is achieved after 1 year with titanium implants which are modified with respect to oxide thickness and surface topography. There is no indication that a reduction of surface roughness, which in the initial phase decreases the rate of bone formation, had any influence on the amount of bone after 1 year in rabbit cortical bone.     

Comparative in vitro study of the proliferation and growth of ovine osteoblast-like cells on various alloplastic biomaterials manufactured for augmentation and reconstruction of tissue or bone defects

In this in vitro study ovine osteoblast-like cells were cultured on seven different alloplastic biomaterials used for augmentation and for reconstruction of bone defects in dental and craniomaxillofacial surgery. The aim of this study was to examine the growth behaviour (viability, cell density and morphology) of ovine osteoblast-like cells on the investigated biomaterials to get knowledge which biomaterial is qualified to act as a cell carrier system in further in vivo experiments. The biomaterials were either synthetically manufactured or of natural origin. As synthetically manufactured biomaterials Ethisorb, MakroSorb, PalacosR, and PDS film were used. As biomaterials of natural origin BeriplastP, Bio-Oss and Titanmesh were investigated. The cell proliferation and cell colonization were analyzed by a proliferation assay and scanning electron microscopy. Osteoblast-like cells proliferated and attached on all biomaterials, except on Beriplast. On Ethisorb the highest cell proliferation rate was measured followed by PalacosR. Both biomaterials offer suitable growth and proliferation conditions for ovine osteoblast-like cells. The proliferation rates of Bio-Oss, MakroSorb, PDS-film and Titanmesh were low and SEM examinations of these materials showed less spread osteoblast-like cells. The results showed that ovine osteoblast-like cells appear to be sensitive to substrate composition and topography. This in vitro study provides the basis for further in vivo studies using the sheep model to examine the biocompatibility and the long-term interaction between the test material and tissue (bone regeneration).     

Investigation of the effect of solidification processing parameters on the rod spacings and variation of microhardness with the rod spacing in the Sn–Cu hypereutectic alloy

Sn–3 wt% Cu hypereutectic alloy was prepared in a graphite crucible under the vacuum atmosphere. The samples were directionally solidified upwards under argon atmosphere with different temperature gradients (G = 4.24–8.09 K/mm) at a constant growth rate (V = 7.64 μm/s) and with different growth rates (V = 2.24–133.33 μm/s) at a constant temperature gradient (G = 4.24 K/mm) by using a Bridgman type directional solidification apparatus. The microstructure of directional solidified Sn–3 wt% Cu alloy seems to be rod eutectic structure. The influence of the growth rate (V) and temperature gradient (G) on the rod spacing (λ) and undercooling (ΔT) were analysed. The values of λ²V, λ²G, ΔTλ, ΔTV^−0.5 and ΔTG^−0.5 were determined by using the Jackson–Hunt eutectic theory. The dependence of microhardness (HV) on the rod spacing (λ) was analyzed. According to present results, it has been found that the value of HV increases with the increasing the value of λ.     

Formulation of ternary complexes of glyburide with hydroxypropyl-β-cyclodextrin and other solubilizing agents and their effect on release behavior of glyburide in aqueous and buffered media at different agitation speeds

Glyburide, a sulfonylurea derivative, widely used as hypoglycaemic agent. In the present study, an attempt has been made to investigate the most effective third component which can be used with hydroxylpropyl-β-cyclodextrin (HPβCd) to form a ternary complex with glyburide in order to enhance its dissolution rate, as well as reduce the amount of HPβCd used for formulating the binary complex with glyburide. Moreover, the objective of this study was also to develop a discriminatory dissolution media in order to discriminate the effect of the different solubilizing agents used for formulating the ternary complex system. Sodium lauryl sulphate, Poloxamer-188, Polyvinylpyrrolidone K-30, lactose and l-arginine were used to formulate ternary system along with HPβCd and glyburide. The ternary system formulated with glyburide:HPβCd:l-arginine in a proportion of 1:1:0.5 has shown the fastest dissolution rate when compared to other solubilizing agents. Unbuffered aqueous media with stirring speed 50?rpm has produced the most discriminatory dissolution profiles. The DSC thermograms and the powder X-ray analysis revealed the decrease in crystallinity of the drug. This was an indication of amorphous solid dispersion or molecular encapsulation of the drug into the cyclodextrin cavity.     

Formulation of ternary complexes of glyburide with hydroxypropyl-β-cyclodextrin and other solubilizing agents and their effect on release behavior of glyburide in aqueous and buffered media at different agitation speeds

Glyburide, a sulfonylurea derivative, widely used as hypoglycaemic agent. In the present study, an attempt has been made to investigate the most effective third component which can be used with hydroxylpropyl-β-cyclodextrin (HPβCd) to form a ternary complex with glyburide in order to enhance its dissolution rate, as well as reduce the amount of HPβCd used for formulating the binary complex with glyburide. Moreover, the objective of this study was also to develop a discriminatory dissolution media in order to discriminate the effect of the different solubilizing agents used for formulating the ternary complex system. Sodium lauryl sulphate, Poloxamer-188, Polyvinylpyrrolidone K-30, lactose and l-arginine were used to formulate ternary system along with HPβCd and glyburide. The ternary system formulated with glyburide:HPβCd:l-arginine in a proportion of 1:1:0.5 has shown the fastest dissolution rate when compared to other solubilizing agents. Unbuffered aqueous media with stirring speed 50?rpm has produced the most discriminatory dissolution profiles. The DSC thermograms and the powder X-ray analysis revealed the decrease in crystallinity of the drug. This was an indication of amorphous solid dispersion or molecular encapsulation of the drug into the cyclodextrin cavity.     

The effect of high-pressure torsion on the behaviour of intermetallic particles present in Al–1Mg and Al–3Mg

The effect of severe plastic deformation on intermetallic particles was investigated using high-pressure torsion on an Al–1Mg–0.2Si–0.2Fe–0.3Mn alloy and an Al–3Mg–0.2Si–0.2Fe–0.3Mn (wt%) alloy. Extensive optical microscopy and scanning electron microscopy was performed to analyse the intermetallic particles using image analysis software. It was found that all the intermetallic particles decreased in size with increasing strain whilst their spatial distribution was homogenised. A greater decrease in size was found for the intermetallic particles present in Al–1Mg alloy and the possible causes are discussed. Even though the strain near the centre of the sample is close to zero, refinement of intermetallic particles is substantial at this location.     

Influence of sintering conditions on the electrical properties and the PTCR effect of the multilayer Ba1.005(Ti1?xNbx)O3 ceramics with Ni internal electrode

The effects of the Nb-dopant content and the sintering conditions on the electrical properties and the positive temperature coefficient of resistance (PTCR) effect of Ba_1.005(Ti_1?xNb_x)O₃ (BTN) ceramics were investigated, which were sintered at 1,070–1,220?°C for 0.5–6?h in a reducing atmosphere and then re-oxidized at 600–750?°C for 1?h. The results indicated that both the sintering temperature and sintering time affected the electrical properties and the PTCR effect of the multilayer BTN samples, whose room-temperature (RT) resistance first reduced and then increased as a function of the donor–doped concentration at all sintering temperature; moreover, the higher the sintering temperature was, the lower the critical dopant concentration. The BTN ceramics showed a remarkable PTCR effect, with a resistance jump greater by 3.3 orders of magnitude, along with a low RT resistance of 0.3?Ω at a low reoxidated temperature of 600?°C after sintering in a reducing atmosphere.     

The effect of a Cr2O3-addition on the phase transformation and catalytic properties of γ-Al2O3 in treatment of lean-burn exhausts

The solid-state thermal behaviour of -Al₂O₃ doped with 10 mol% Cr (oxide) was studied with respect to phase-transition behaviour and the co-ordination of the dopant Cr cations. A series of transformations: -Al₂O₃ -Al₂O₃ -Al₂O₃ -Al₂O₃ was observed for Cr₂O₃-doped alumina samples between 500 °C and 1100 °C. Rapid grain growth occurred at temperatures close to 1100 °C. The electron spin resonance (ESR) spectra for the sample heat-treated at 500 °C corresponded to the resonance of -Cr³⁺ in an amorphous Cr oxide impregnated onto the - and -alumina support. The change of ESR spectrum indicated the existence of Cr³⁺, suggesting the formation of a solid solution with the same structures as -Al₂O₃ and/or -Al₂O₃ at 800–1000 °C. The evaluation of catalytic activities for model exhaust was performed under lean-burn (an excess of oxygen) condition of air/fuel ratio A/F = 18 and space velocity SV = 100 000 h^–1 . The modified Al₂O₃ catalyst heat-treated at 1000 °C in air showed removal conversion of 100% for hydrocarbon (C₃H₆), 92% for CO and 5% for NO at 550 °C. Present results suggest that Cr-modification to Al₂O₃ leads to catalytic improvement with good thermal durability.     

Evidence for a Self-bound Liquid State and the Commensurate–Incommensurate Coexistence in 2D 3He on Graphite

We made heat-capacity measurements of two dimensional (2D) ³He adsorbed on graphite preplated with monolayer ⁴He in a wide temperature range (0.1≤T≤80 mK) at densities higher than that for the 4/7 phase (=6.8 nm^?2). In the density range of 6.8≤ρ≤8.1 nm^?2, the 4/7 phase is stable against additional ³He atoms up to 20% and they are promoted into the third layer. We found evidence that such promoted atoms form a self-bound 2D Fermi liquid with an approximate density of 1 nm^?2 from the measured density dependence of the γ-coefficient of heat capacity. We also show evidence for the first-order transition between the commensurate 4/7 phase and the ferromagnetic incommensurate phase in the second layer in the density range of 8.1≤ρ≤9.5 nm^?2.     

Effect of Al<Superscript>3+</Superscript> modification on cobalt ferrite and its impact on the magnetoelectric effect in BCZT–CFO multiferroic composites

One of the methods to enhance the functional properties of two-phase multiferroic magnetoelectrics is to increase magnetostriction of the ferrite phase. Al³⁺-modified cobalt ferrite Co(Al_0.5Fe_1.5)O₄ shows better magnetostriction than unmodified cobalt ferrite. It is used in combination with (Ba,Ca)(Zr,Ti)O₃ which has very good piezoelectric properties, to form a multiferroic composite. The composite shows good magnetoelectric characteristics, both macroscopically (converse magnetoelectric coefficient of 11 ps/m) and microscopically. Al³⁺ proves to be the best non-magnetic dopant to enhance magnetostriction in CoFe₂O₄ and thus the magnetoelectric coefficient.     

Influence of nanoparticle addition on the formation and growth of intermetallic compounds (IMCs) in Cu/Sn–Ag–Cu/Cu solder joint during different thermal conditions

Abstract

Nanocomposite lead-free solders are gaining prominence as replacements for conventional lead-free solders such as Sn–Ag–Cu solder in the electronic packaging industry. They are fabricated by adding nanoparticles such as metallic and ceramic particles into conventional lead-free solder. It is reported that the addition of such nanoparticles could strengthen the solder matrix, refine the intermetallic compounds (IMCs) formed and suppress the growth of IMCs when the joint is subjected to different thermal conditions such as thermal aging and thermal cycling. In this paper, we first review the fundamental studies on the formation and growth of IMCs in lead-free solder joints. Subsequently, we discuss the effect of the addition of nanoparticles on IMC formation and their growth under several thermal conditions. Finally, an outlook on the future growth of research in the fabrication of nanocomposite solder is provided.     

Metastable CoSn<Subscript>4</Subscript> formation induced by minor Ga addition and effective suppression effect on the IMC growth in solid-state Sn–Ga/Co reactions

Solid-state interfacial reactions between Co and Sn-based solders doped with different levels of Ga (0.02 to 0.5 wt%) were investigated. With minor Ga addition of less than 0.05 wt%, the CoSn₃ layer was uniformly formed at the interface. Compared to the pure Sn/Co reaction, the CoSn₃ growth was greatly suppressed by 95 % with only 0.02 wt%Ga addition at 160 °C. The growth kinetics of CoSn₃ were systematically studied at temperatures of 160 to 200 °C. The CoSn₃ phase clearly exhibited a linear growth with aging time and the suppression effect was more significant with decreasing the aging temperature. It could be attributed to the fact that Ga atoms doped in the CoSn₃ phase retarded the nucleation and growth of CoSn₃. In particular, with 0.1 wt%Ga addition, the reaction layer changed to the metastable CoSn₄ phase, rather than CoSn₃. Most importantly, the CoSn₄ growth was also strongly suppressed. It was only ~3-μm thick at 180 °C even after aging for 480 h. Similarly, a thin layer of CoSn₄ was formed in the reactions with 0.2 to 0.4 wt%Ga. When the Ga content was increased to 0.5 wt%, the dominant reaction phase changed to the CoGa, which was very thin and stably present at the interface. The CoSn₄ and α-CoSn₃ phases with similar orthorhombic crystal structures and the reasons for the phase change were further discussed.     

Pyrochlore phase in the Bi2O3–Fe2O3–WO3–(H2O) system: Physicochemical and hydrodynamic aspects of its production using a microreactor with intensively swirled flows

The present work deals with a study of physicochemical and hydrodynamic aspects of a new approach to the synthesis of a (Bi, Fe, □)₂(Fe, W)₂O₆O′_δ cubic pyrochlore-structured phase (hereinafter BFWO) in the Bi₂O₃–Fe₂O₃–WO₃–(H₂O) system. The considered approach is based on the use of microreactor technology at the stage of obtaining the amorphous precursor suspension, which is subsequently hydrothermally treated. The amorphous precursor suspension was obtained by co-precipitation method using two techniques of mixing reagent solutions, namely (i) by dropwise supply (traditional laboratory technique), and (ii) by intensive co-precipitation in a microreactor with a continuous supply of swirling flows of reagent solutions (microreactor technology with a suspension output of ∼ 7 L/min). It is shown that the microreactor strategy made it possible to avoid the spatial isolation of components during the amorphous precursor formation, which further ensured the formation of crystals of only the BFWO phase (without impurities). The values of the band gap (E_g) for direct allowed electronic transitions are 2.40 ± 0.03 and 2.35 ± 0.03 eV for the microreactor case and for the dropwise supply, respectively, which permits characterization of the obtained materials as wide bandgap semiconductors.