Formulation studies on ibuprofen sodium–cationic dextran conjugate: effect on tableting and dissolution characteristics of ibuprofen

The effect of electrostatic interaction between ibuprofen sodium (IbS) and cationic diethylaminoethyl dextran (Ddex), on the tableting properties and ibuprofen release from the conjugate tablet was investigated. Ibuprofen exhibits poor flow, compaction (tableting) and dissolution behavior due to its hydrophobic structure, high cohesive, adhesive and viscoelastic properties therefore it was granulated with cationic Ddex to improve its compression and dissolution characteristics. Electrostatic interaction and hydrogen bonding between IbS and Ddex was confirmed with FT-IR and DSC results showed a stepwise endothermic solid–solid structural transformation from racemic to anhydrous forms between 120 and 175?°C which melted into liquid form at 208.15?°C. The broad and diffused DSC peaks of the conjugate granules as well as the disappearance of ibuprofen melting peak provided evidence for their highly amorphous state. It was evident that Ddex improved the flowability and densification of the granules and increased the mechanical and tensile strengths of the resulting tablets as the tensile strength increased from 0.67?±?0.0172 to 1.90?±?0.0038?MPa with increasing Ddex concentration. Both tapping and compression processes showed that the most prominent mechanism of densification were particle slippage, rearrangement and plastic deformation while fragmentation was minimized. Ddex retarded the extent of dissolution in general, indicating potentials for controlled release formulations. Multiple release mechanisms including diffusion; anomalous transport and super case II transport were noted. It was concluded that interaction between ibuprofen sodium and Ddex produced a novel formulation with improved flowability, tableting and dissolution characteristics with potential controlled drug release characteristics dictated by Ddex concentration.     

The effect of ionic dissolution products of Ca–Sr–Na–Zn–Si bioactive glass on in vitro cytocompatibility

Many commercial bone grafts cannot regenerate healthy bone in place of diseased bone. Bioactive glasses have received much attention in this regard due to the ability of their ionic dissolution products to promote cell proliferation, cell differentiation and activate gene expression. Through the incorporation of certain ions, bioactive glasses can become therapeutic for specific pathological situations. Calcium–strontium–sodium–zinc–silicate glass bone grafts have been shown to release therapeutic levels of zinc and strontium, however the in vitro compatibility of these materials is yet to be reported. In this study, the in vitro cytocompatibility of three different calcium–strontium–sodium–zinc–silicate glasses was examined as a function of their ion release profiles, using Novabone® bioglass as a commercial comparison. Experimental compositions were shown to release Si⁴⁺ ranging from 1 to 81 ppm over 30 days; comparable or enhanced release in comparison to Novabone. The maximum Ca²⁺ release detected for experimental compositions was 9.1 ppm, below that reported to stimulate osteoblasts. Sr²⁺ release was within known therapeutic ranges, and Zn²⁺ release ranged from 0.5 to 1.4 ppm, below reported cytotoxic levels. All examined glass compositions show equivalent or enhanced in vitro compatibility in comparison to Novabone. Cells exposed to BT112 ionic products showed enhanced cell viabilities indicating cell proliferation was induced. The ion release profiles suggest this effect was due to a synergistic interaction between certain combinations and concentrations of ions. Overall, results indicate that the calcium–strontium–sodium–zinc–silicate glass compositions show equivalent or even enhanced in vitro compatibility compared to Novabone®.     

Formulation and Comparative Characterization of Chitosan,Gelatin, and Chitosan–Gelatin-Coated Liposomes of CPT-11–HCl

Liposomes containing phosphatidylcholine and cholesterol (uncoated) and coated by chitosan, gelatin, and combination of chitosan and gelatin were prepared by the modified ethanol injection method. The aim of this work was to formulate and characterize liposomes of camptothecin (CPT)-11–HCl (Irinotecan HCl) containing chitosan, gelatin, and both polymers as coating materials; and also to increase its circulation longevity when compared with the free drug while maintaining the agent in its active lactone form. Size, shape, zeta potential, encapsulation efficiency, stability study, in vitro, and in vivo release study were used for characterization of liposomes. The size of liposomes was in the order of uncoated?<?chitosan coated?<?gelatin coated?<?combination of chitosan and gelatin coated. The zeta potential of liposomes was in the order of combination of chitosan and gelatin coated?>?chitosan coated?>?gelatin coated?>?uncoated. The formulations showed the long-term stability. The encapsulation efficiency of liposomes was in order of combination of chitosan and gelatin coated?>?gelatin coated?>?chitosan coated?>?uncoated. The in vitro and in vivo release of drug was observed in the order of combination chitosan and gelatin coated?>?gelatin coated?>?chitosan coated?>?uncoated.     

The role of C–H⋯O hydrogen-bonding interactions in the solid-state packing of squaraine dyes

The role of C–H⋯O hydrogen-bonding interactions in the solid-state packing networks of squaraine dyes has been investigated by re-examining the nine previously published X-ray crystal structures of these materials. In addition, two new compounds, 2,4-bis(1-hexyl-3,3-dimethyl-2-indolinylidenemethyl)cyclobutenebis(ylium)-1,3-diolate and 2,4-bis(1-(ethan-2-ol)-3,3-dimethyl-2-indolinylidenemethyl)cyclobutenebis(ylium)-1,3-diolate, have had their structures determined and lattice packings discussed with respect to their hydrogen-bonding networks. Analysis of the eleven structures shows, in seven cases, two emergent packing motifs. All structures exhibit molecules in stacked columns, but the two differing patterns arise from specific intermolecular C–H⋯O associations which are directed at the molecules of either an adjacent parallel column or a column of opposing direction. In the four structures which do not exhibit either of these two packing arrangements, hydrogen-bonding associations are still important in the analysis of the overall lattice network.     

The precipitation behaviours and strengthening mechanism of a Cu-0.4 wt％Sc alloy

The precipitation behaviours during the aging process and the corresponding strengthening mechanism of a Cu-0.4 wt％Sc alloy were systematically investigated in ...     

Room-temperature ferromagnetic and photoluminescence properties of indium–tin-oxide nanoparticles synthesized by solid-state reaction

In the present study, indium–tin-oxide (ITO) nanoparticles were synthesized using solid-state reaction and studied for their structural, vibrational and magnetic properties. The ITO nanoparticles were prepared under reduced pressure, which can increase the oxygen vacancies in the samples. The X-ray diffraction studies confirmed singe-phase cubic bixbyite structure of ITO with average crystallite size of 47 nm. The lattice vibrational studies (FT-IR and Raman spectroscopy) at room temperature indicated that Sn ions were occupied in In₂O₃ lattice and gives corresponding active vibrational modes in the respective spectra. The magnetic studies at room temperature reveal the ferromagnetic nature of ITO and the strength of magnetization is superior to those of In₂O₃ and SnO₂. However, the magnetic studies at 100 K revealed reduced ferromagnetism, which could be attributed to reduced itinerary electrons at low temperature. Blue and blue–green emissions were found from the ITO nanoparticles, which could be due to vacancies or surface defects present in the system.     

The solid-state packing of sulfur substituted 2-aminopyrimidines and the occurrence of N-H—S hydrogen-bonding associations

The solid-state packing arrays of eight 4-sulfur substituted 2-aminopyrimidines have been examined and the occurrence of N–H—S hydrogen-bonding associations in those structures discussed. The eight compounds were 2,5-diamino-4-mercapto-6-methylpyrimidine 1, 2-amino-4,6-bis(phenylthio)pyrimidine 2, 2-amino-4,6-bis(4-chlorophenylthio)pyrimidine 3, 2-amino-4,6-bis(4-methylphenylthio)pyrimidine 4, 5 (two polymorphs), 2-amino-4-chloro-6-(4-fluorophenylthio)pyrimidine 6, 2-amino-4-(4-chlorophenylthio)-6-morpholinopyrimidine 7, 2-amino-4-(4-(2,3-dimethylphenyl)piperizino)-6-phenylthiopyrimidine 8, and 2-amino-4-(4-(2-ethoxyphenyl)piperizino)-6-(4-chlorophenylthio)pyrimidine 9. The single-crystal x-ray structures of 1 – 3 have been previously reported while the structures of 4 – 9 are presented in this paper. All packing motifs exhibit characteristic R₂²(8) hydrogen-bonded 2-aminopyrimidine dimers, to varying degrees of polymerisation, whereas compounds 1 – 5 and 7 include N–H—S associations, the majority of which are three-center associations with an included N–H—N interaction.     

Effect of HCl concentrations on apatite-forming ability of NaOH–HCl- and heat-treated titanium metal

Titanium (Ti) metal was treated with water or HCl solutions after 5 M NaOH solution treatment and then subjected to heat treatment at 600°C. The apatite-forming abilities of the treated Ti metals were examined in simulated body fluid. The apatite-forming ability of the Ti metal subjected to NaOH, water and heat treatment was lower than that of just NaOH and heat treatments. Ti metals subjected to NaOH, HCl and heat treatment showed apatite-forming abilities, which increased with increasing HCl concentrations up to the same level as that of NaOH- and heat-treated Ti metal. The former did not show a decrease in its apatite-forming ability, even in a humid environment for a long period, whereas the latter decreased its ability. The increase in the apatite-forming ability with increasing HCl concentrations suggests a different mechanism of apatite formation from that previously proposed.     

One-step generation of Greenberger–Horne–Zeilinger states of multi solid-state spin qubits

We propose a one-step scheme for the generation of Greenberger–Horne–Zeilinger states of multi solid-state qubits and the implementation of quantum phase gates in a system consisting of N spatially separated nitrogen-vacancy centers coupled to the whispering-gallery mode (WGM) of a microsphere cavity. The proposed scheme is based on the effective electronic dipole–dipole interaction between electron spins associated with the NV centers, which is mediated by the WGM and applying external driving laser fields. As the spontaneous emission of the excited states of the NV centers is highly suppressed and the cavity mode is only virtually excited, the scheme is insensitive to decoherence.     

Preparation and characterization of PAN–KI complexed gel polymer electrolytes for solid-state battery applications

The free standing and dimensionally stable gel polymer electrolyte films of polyacrylonitrile (PAN): potassium iodide (KI) of different compositions, using ethylene carbonate as a plasticizer and dimethyl formamide as solvent, are prepared by adopting ‘solution casting technique’ and these films are examined for their conductivities. The structural, miscibility and the chemical rapport between PAN and KI are investigated using X-ray diffraction, Fourier transform infrared spectroscopy and differential scanning calorimetry methods. The conductivity is enhanced with the increase in KI concentration and temperature. The maximum conductivity at 30°C is found to be 2.089 × 10^?5 S cm^?1 for PAN:KI (70:30) wt%, which is nine orders greater than that of pure PAN (< 10^?14 S cm^?1). The conductivity-temperature dependence of these polymer electrolyte films obeys Arrhenius behaviour with activation energy ranging from 0.358 to 0.478 eV. The conducting carriers of charge transport in these polymer electrolyte films are identified by Wagner’s polarization technique and it is found that the charge transport is predominantly due to ions. The better conducting sample is used to fabricate the battery with configuration K/PAN + KI/I₂+ C + electrolyte and good discharge characteristics of battery are observed.     

Liquid-state and solid-state interfacial reactions between Sn–Ag–Cu–Fe composite solders and Cu substrate

The growth kinetics and morphology of the interfacial intermetallic compound (IMC) between Sn–3Ag–0.5Cu–xFe (x = 0, 0.5 wt%, 1 wt%) composite solders and Cu substrate were investigated in the present work. The Sn–Ag–Cu–Fe/Cu solder joint were prepared by reflowing for various durations at 250 °C and then aged at 150 °C. During soldering process, Fe particles quickly deposited in the vicinity of IMC, resulting in the formation of Fe-rich area. Isothermal equation of chemical reaction and phase diagrams were used to explain the effect of Fe on the growth kinetics of IMC during liquid-state interfacial reaction. It was shown that Fe could effectively retard the growth of interfacial Cu₆Sn₅ and Cu₃Sn layers during liquid-state reaction and reduce the size of Cu₆Sn₅ grains. Small cracks were observed in the Cu₆Sn₅ grains after reflowing for 2 min while they were found in the other composite solders reflowing for about 30 min. The Fe tended to suppress the growth of the Cu₃Sn layer during solid-state aging. However, the total thickness of IMCs (Cu₆Sn₅ + Cu₃Sn) for the composite solders with Fe particles was similar to that for SnAgCu without Fe particles.     

Effects of chitosan molecular weight on the physical and dissolution characteristics of amorphous curcumin–chitosan nanoparticle complex

Objective: To investigate the effects of varying molecular weight (MW) of chitosan (CHI) used in the complexation with curcumin (CUR) on the physical and dissolution characteristics of the amorphous CUR–CHI nanoparticle complex produced.

Significance: Amorphous CUR–CHI nanoparticle complex (or CUR nanoplex in short) recently emerged as a promising bioavailability enhancement strategy of CUR attributed to its fast dissolution, supersaturation generation capability, and simple preparation. Existing CUR nanoplex prepared using low MW CHI, however, exhibited poor colloidal stability during storage. Herein we hypothesized that the colloidal stability could be improved by using CHI of higher MW. The effects of this approach on the nanoplex’s other characteristics were simultaneously investigated.

Methods: The CUR nanoplex was prepared by electrostatically driven self-assembled complexation between CUR and oppositely charged CHI of three different MWs (i.e. low, medium, and high). Besides colloidal stability, the effects of MW variation were investigated for the nanoplex’s (1) other physical characteristics (i.e. size, zeta potential, CUR payload, amorphous state stability), (2) preparation efficiency (i.e. CUR utilization rate, yield), and (3) dissolutions under sink condition and supersaturation generation.

Results: CUR nanoplex prepared using CHI of high MW exhibited improved colloidal stability, larger size, superior morphology, and prolonged supersaturation generation. On the other hand, the effects of MW variation on the payload, amorphous state stability, preparation efficiency, and dissolution under sink condition were found to be insignificant.

Conclusions: Varying MW of CHI used was an effective means to improve certain aspects of the CUR nanoplex characteristics with minimal adverse effects on the others.     

Gefitinib–cyclodextrin inclusion complexes: physico-chemical characterization and dissolution studies

Background: Gefitinib, an anticancer drug, has an extremely low aqueous solubility, and its oral absorption is limited by its dissolution rate. The solubility and dissolution of gefitinib can be improved by complexation with cyclodextrins (CDs). Methods: Phase solubility studies of gefitinib with hydroxypropyl βCD (HPβCD) and randomly methylated βCD (RMβCD) in n various aqueous systems was conducted to characterize the complexes in the liquid state. The inclusion complexes in the solid state were prepared by freeze-drying method and characterized by X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC). Results: Gefitinib formed stable complexes with HPβCD and RMβCD in distilled water as indicated by the association rate constants (Ks) of 458.9 and 1096.2 M^?1 for HPβCD and RMβCD, respectively. The complexation of gefitinib with CDs in pH 4.5 acetate buffer indicated an A_N type of phase-solubility diagrams, whereas gefitinib and HPβCD in distilled water in the presence of polymers such as polyvinyl pyrrolidone K-30 (PVP) or hydroxypropyl methylcellulose E3 (HPMC) resulted in A_P-type phase-solubility diagrams. The solid-state amorphous complexes (as described by DSC and X-RD) showed substantial increases in the solubility and dissolution rate of gefitinib with both CDs. Further increases in the solubility and dissolution rate of the gefitinib-HPβCD freeze-dried complex were obtained by physically mixing the complex with PVP and HPMC. Conclusion: Gefitinib formed stable inclusion complexes with HPβCD and RMβCD, and the solubility and dissolution rate of the drug was significantly increased.     

Solvents effects on crystallinity and dissolution of β-artemether*

β-artemether (ARM) is a widely used anti-malarial drug isolated from the Chinese antimalarial plant, Artemisia annua. The solvent effects on crystal habits and dissolution of ARM were thoroughly investigated and discussed herein. The ARM was recrystallized in nine different solvents of varied polarity, namely, methanol, ethanol, isopropanol, tetrahydrofuran, dichloromethane, trichloromethane, ethyl acetate, acetone and hexane by solvent evaporation method. The obtained crystals were morphologically characterized using scanning electron microscope (SEM). The average sizes of crystals were 1.80–2.64?μm calculated from microscopic images using Image-Pro software. No significant change in chemical structure was noticed after recrystallization and the specific band at 875?cm^?1 wavenumber (C–O–O–C) confirmed the presence of most sensitive functional group in the ARM chemical structure. The existence and production of two polymorphic forms, polymorph A and polymorph B, was confirmed by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The data suggested that the fabrication of polymorph B can be simply obtained from the recrystallization of ARM in a specific solvent. Significant effects of solvent polarity, crystals shapes and sizes on drug dissolution were noticed during in vitro dissolution test. The release kinetics were calculated and well fitted by the Higuchi and Hixon–Crowell models. The ARM-methanol and ARM-hexane showed highest and slowest dissolution, respectively, due to the effects of solvent polarity and crystal morphologies. Overall, proper selection of the solvents for the final crystallization of ARM helps to optimize dissolution and bioavailability for a better delivery of anti-malarial drug.     

Effect of temperature on high-cycle fatigue and very high cycle fatigue behaviours of a low-strength Cr–Ni–Mo–V steel welded joint

Axially push–pull fatigue tests of a low-strength Cr–Ni–Mo–V steel welded joint were conducted up to very high cycle fatigue regime at room temperature and 370 °C. The S–N curve at room temperature shows a duplex shape, while the S–N curve at 370 °C is continuously decreasing with lower fatigue strength. The welds at 370 °C undergoes dynamic strain ageing and has an enhanced load–defects interaction, leading to equal distribution of failures among different parts of the welds. The Z parameter model, with micro-defect location incorporated, having sound physical representation, is life-controlling of the welds at high temperature.     

The role of cementite in the metal dusting of Fe–Cr and Fe–Ni–Cr Alloys

Abstract

Model Fe–25 w/o (weight percent) Cr and Fe–25 Cr–Ni alloys containing 2.5, 5, 10 and 25w/o nickel were exposed to a CO–26H₂–6H₂O (vol. pct) mixture at 680°C under thermal cycling conditions. The supersaturated carbon activity was calculated to be 2.9 (referred to graphite) and M₃C was predicted to form on Fe–25Cr and Fe–25 Cr–2.5 Ni, but not on higher nickel content alloys. Metal dusting occurred on all alloys, accompanied by internal carburisation. Transmission electron microscopy of the dusting deposit showed that much of the carbon consisted of hollow graphite nanotubes. Small, metal-rich particles were found at the carbon filament tips. These were identified as single crystal Fe₃C in the case of Fe–25 Cr, and M₃C, containing low levels of nickel, in the case of Fe–25 Cr–2.5 Ni and Fe–25 Cr–5 Ni. In contrast, the particles found at the filament tips on the higher nickel, two phase, alloys were both M₃C and austenitic Fe–Ni. Strong orientation relationships were determined between the graphite and cementite particles, however, no consistent and clear crystallographic relationship was deduced between the graphite and austenite particles. It is concluded that carbon deposition from the gas is catalysed by both Fe₃C and austenite. Subsequent carbon nanotube growth reflects the orientation relationship between Fe₃C and the graphite.     

The Effect of Sn Substitution of Pb on Microstructure and Superconducting Properties of Bi–Pb–Sr–Ca–Cu–O Superconductor

The effect of substitution of Pb by Sn in Bi_1.6Pb_0.4?x Sn _x Sr₂Ca₂Cu₃ O _δ samples at x = 0.0, 0.1, 0.2, and 0.3 on the critical transition temperature and structural properties was investigated in this work. All the samples were prepared by the solid-state reaction method. The prepared samples were characterized by X-ray diffraction (XRD), resistance–temperature curve (R–T), scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). The Sn ⁴⁺ substitution of Pb ²⁺ caused significant changes in the properties of the samples. The formation of the (Bi, Pb)-2212 phase was stabilized and the T _c (onset) was improved at the x = 0.2 level of Sn ⁴⁺ substitution. The SEM micrographs have shown that the structure of the sample with x = 0.2 became more dense. However, samples with x = 0.1 and 0.3 have not shown zero resistance by EDS analysis because of oxygen deficiency.     

The static and cyclic strength of a bone–cement bond

Four-point bending static and fatigue tests were carried out on bone–cement bonds. The effects of the pressurization and the washing of the bone joint face on the bond strength were investigated. The results are summarized as follows. When the bond surface of cancellous bone is washed prior to the application of the bone cement, both the static and fatigue strengths of the bond are increased relative to the corresponding properties of unwashed bone–cement bonds. From observations of bone–cement interfaces as well as the fracture surfaces of bone–cement specimens, it has been determined that bone cement was able to infiltrate into fine holes present in washed cancellous bone. However, such infiltration occurred to a much lesser degree in the case of unwashed cancellous bone. Increasing the molding pressure during the time of cement application to the bone from 39200 to 117600 Pa had a beneficial effect on the bending strength and fatigue properties, particularly in the case of washed bone cement specimens. An increase in molding pressure also resulted in a reduction in the amount of scatter in test results.     

Enhancement of dissolution rate and bioavailability of sulfamethoxazole by complexation with β-cyclodextrin

The purpose of this study was to improve the solubility and dissolution rate of sulfamethoxazole (SMZ) with inclusion compound of β-cyclodextrin (β-CD). The interaction between SMZ and β-CD in solution was studied by the phase-solubility method. The phase-solubility studies revealed the formation of inclusion complexes with poor solubility with an inclusion complex of 1:1 molar ratio and a stability constant of 122.3?M(-1). The solid complexes of SMZ with β-CD were prepared by using kneading and coprecipitation methods. The physical mixture of these chemicals was also prepared for comparison. Inclusion complexation was confirmed by the results from the studies of infrared spectoroscopy (IR) and differential scanning calorimetry (DSC). The effect of water-soluble polymers i.e., polyethylene glycol 20000 and non-ionic surfactants i.e., polysorbate 20 on the complexation of SMZ with β-CD was also investigated by the same methods. The rates of release of the active material from the complexes were determined from dissolution studies using USP XXII paddle method. The formulation, that provided delivery of active material near to the target value in six healthy volunteers and in vivo tests, clearly revealed that the bioavailability of active material was found to be enhanced by preparing ternary mixtures.