Slow Dissolution Research Articles

Preparation of meloxicam-salicylic acid co-crystal and its application in the treatment of rheumatoid arthritis

Meloxicam is a non-steroidal anti-inflammatory drug that can selectively inhibit cyclooxygenase 2 (COX-2), showing high anti-inflammatory activity, low gastrointestinal and renal side effects. However, the low solubility and slow dissolution rate limit its role in rapid pain relief. In this paper, using meloxicam as the active drug molecule and salicylic acid as the co-crystal former, the meloxicam-salicylic acid co-crystal (MLX-SLC CoC) was prepared by the reaction crystallization method. The co-crystal was characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The dissolution curve of the co-crystal was determined, and the result showed that the formation of drug co-crystal enhanced the solubility and dissolution rate of MLX. The oil-water partition coefficient of the MLX-SLC CoC was determined, and the results showed that the oil-water partition coefficient of the co-crystal was similar to that of pure MLX. The gel prepared by MLX-SLC CoC was used to study its in vitro release and transdermal penetration characteristics were investigated, which showed that the transdermal penetration of the drug was increased without affecting its in vitro release. Preparation of gel in the form of MLX-SLC CoC increased the drug concentration in the gel. Finally, the therapeutic effect of the gel on arthritis was preliminarily studied by establishing a rheumatoid arthritis rat model.

The overlooked mechanism of chalcopyrite passivation

Chalcopyrite (CuFeS₂) is the world's main source of copper. Electrification of the global economy will rely on economically viable Cu dissolution from low grade chalcopyrite ores, but this process is particularly slow. The reason for this slow reaction has been in dispute for over 50 years. In this study, electrochemical analysis showed that n-type chalcopyrite is in an accumulation state when immersed in electrolyte, not in a depletion state as is commonly assumed. A leaching test and surface analysis confirmed the formation of a Cu-rich surface layer during oxidative leaching. In addition, a similar leaching test on covellite (CuS) showed leaching kinetics that were as slow as chalcopyrite. Ex-situ current-voltage analysis showed that the Cu-rich (covellite-like) product layer on the surface of chalcopyrite was a p-type semiconductor. Therefore, as leaching progresses, chalcopyrite transitions from a resistor to a diode. Three mechanisms for slow dissolution of chalcopyrite in acidic ferric media are proposed based on these tests: 1. The dielectric breakdown potential of chalcopyrite (0.7 V vs Ag/AgCl) is higher than what the ferric/ferrous redox couple can provide (0.5 V). 2. A chemically stable covellite-like surface layer prevents further Cu dissolution. 3. Rapid formation of a p-n junction on the leached chalcopyrite surface hinders the electrochemical process. We hypothesize that all three mechanisms together prevent the full dissolution of chalcopyrite under oxidative conditions at ambient temperature.

Toxicokinetics of Nanoparticles Deposited in Lungs Using Occupational Exposure Scenarios.

Various synthetic powders with primary particle sizes at the nanoscale and a high commercial impact have been studied using Wistar rats. The test materials were metal oxides, i.e., TiO2, ZnO and amorphous silica, and carbon black (technical soot). Dosing schemes were in the regular ranges typically used in subacute rat studies to simulate occupational exposure scenarios (mg range). Nanoscaled particle agglomerates have the potential to disintegrate and translocate as individual nanoparticles to remote locations following deposition in the lungs. The toxicokinetic fate of metal oxides post-inhalation in lungs/organs was investigated (i) by chemical analysis of the retained particulate/dissolved matter and (ii) by visualization of particles in various remote organs using transmission electron microscopy (TEM). The three titanium dioxides (NM-103, NM-104, NM-105; JRC coding) showed a very slow dissolution in lung fluids. In contrast, the coated ZnO (NM-111) dissolved quickly and was eliminated from the body within approximately 1 day. The precipitated amorphous silica (NM-200) showed a partial dissolution. Chemical analysis in lungs (particulate and soluble TiO2) and in remote organs (liver and brain) showed a small solubility effect under physiological conditions. The translocation to remote organs was negligible. This confirms that for poorly soluble TiO2 particles there was no considerable translocation to the liver and brain. The chemical analysis of zinc demonstrated a very rapid dissolution of ZnO particles after deposition in the lungs. Statistically significant increases in Zn levels in the lungs were detectable only on day 1 post-exposure (NM-111). Overall, no relevant amounts of increased NM-111 in the ionic or particulate matter were detected in any body compartment. Amorphous silica (NM-200) particles were found in the cytoplasm of intraalveolar macrophages in the lung and the cytoplasm of macrophages in the lung associated lymph node. Interestingly, these particles were found in a few animals of all treatment groups (1, 2.5, and 5 mg/m3 NM-200) even after 91 days post-exposure. In all other organs of the NM-200 treated animals such as the nasal epithelium, trachea, larynx, liver, spleen, kidney, and mesenteric lymph node no particles were found at any time point investigated. Carbon black was tagged internally (“intrinsically”) with a γ tracer (7beryllium; half-time: 53.3 days). Due to limited amounts, the test item (0.3 mg per rat lung) was intratracheally instilled into the lungs. This dose avoided a particle overload effect, meaning that the toxicokinetic fate of carbon black could be followed under the approximated physiological conditions of lung clearance. Analysis of the γ labeled carbon black confirmed conclusively that there was no evidence for the translocation of carbon black beyond the lung into the blood or other body compartments. Very small amounts were only detected in lung-associated lymph nodes (LALN). On day 20 post-treatment, upon necropsy, both carbon black samples were practically exclusively found in lungs (75.1% and 91.0%, respectively) and in very small amounts in the lung-associated lymph nodes (LALN), i.e., ~0.5%. In the other organs/tissues, the test item was not significantly detectable. Separation of leukocytes and cell-free supernatant of a bronchoalveolar lavagate by centrifugation revealed that carbon black was completely located in the cell sediment, indicating total engulfment by alveolar macrophages. In conclusion, in occupational settings the nanomaterials titanium dioxide, zinc oxide, amorphous silica, and carbon black acted as microscaled agglomerates, not as individual nanoparticles. They displayed no potential to translocate beyond the lung into the blood compartment. Besides lungs, very small particulate amounts were detected only in LALN. This finding is consistent with the behavior of microscaled poorly soluble particles. Overall, there was no evidence of translocation of the nanomaterials following pulmonary exposures.

Particle Agglomeration of Acid-Modified Tapioca Starches: Characterization and Use as Direct Compression Fillers in Tablets.

Acid-modified tapioca starches (AMTSs) possessed good compressibility but showed poor particle flowability for preparing tablets by the direct compression method. The aims of this work were to prepare and characterize AMTS agglomerates using polyvinylpyrrolidone (PVP) as an agglomerating agent. The dilution potential and stability studies of the AMTS agglomerates were investigated. The results showed that particle enlargement of TS and AMTS could be achieved via agglomeration using PVP. The thermal behavior and molecular interaction of the agglomerates were revealed using DSC and FTIR spectroscopy, respectively. An increase in PVP concentrations resulted in greater particle strength of the TS agglomerates and a higher acid concentration for modification enhanced the strength of the AMTS agglomerates. All agglomerates presented good particle flowability. Moreover, the AMTS agglomerates provided higher compressibility hardness than the TS agglomerates. The addition of PVP could extend the disintegration time and slow drug dissolution from the agglomerate tablets. The humidity of the storage conditions influenced the thickness and hardness of the AMTS agglomerate tablets, and good physical and chemical stability of the tablets was obtained under ambient conditions and in the refrigerator. Furthermore, the AMTS agglomerates displayed good carrying capacity and possessed desirable characteristics for use in direct compression tablets.

Lipid based Vehicles and Lipid-based Excipients in Drug delivery

In recent years, there has been increasing interest in the use of formulations containing lipid-based excipients that comprise combinations of synthetic or semisynthetic lipids with surfactants, co-surfactants or co-solvents. This review is generally focussed on lipid-based excipients in pharmaceutical formulations which improves the oral bioavailability of poorly water-soluble drugs. Lipid-based formulations can reduce the limitations of slow and incomplete dissolution of poorly water-soluble drugs, and facilitate the formation of solubilised phases from which absorption may occur. The improvement of bio-availability of drugs is one of the greatest challenges in drug formulations. This review discusses novel lipids like Compritol 888 ATO, Dynasan 114, Glyceryl monooleate (GMO), Maisine CC and Precirol ATO 5 focussing on how these can be employed for devising efficient drug delivery systems and also the in vivo effect and fate of lipid excipients.

Dissolution Rate of Nanomaterials Determined by Ions and Particle Size under Lysosomal Conditions: Contributions to Standardization of Simulant Fluids and Analytical Methods.

Dissolution of inhaled engineered nanomaterials (ENM) under physiological conditions is essential to predict the clearance of the ENM from the lungs and to assess their biodurability and the potential effects of released ions. Alveolar macrophage (AM) lysosomes contain a pH 4.5 saline brine with enzymes and other components. Different types of artificial phagolysosomal simulant fluids (PSFs) have been developed for dissolution testing, but the consequence of using different media is not known. In this study, we tested to which extent six fundamentally different PSFs affected the ENM dissolution kinetics and particle size as determined by a validated transmission electron microscopy (TEM) image analysis. Three lysosomal simulant media were consistent with each other and with in vivo clearance. These media predict the quick dissolution of ZnO, the partial dissolution of SiO2, and the very slow dissolution of TiO2. The valid media use either a mix of organic acids (with the total concentration below 0.5 g/L, thereof citric acid below 0.15 g/L) or another organic acid (KH phthalate). For several ENM, including ZnO, BaSO4, and CeO2, all these differences induce only minor modulation of the dissolution rates. Only for TiO2 and SiO2, the interaction with specific organic acids is highly sensitive, probably due to sequestration of the ions, and can lead to wrong predictions when compared to the in vivo behavior. The media that fail on TiO2 and SiO2 dissolution use citric acid at concentrations above 5 g/L (up to 28 g/L). In the present selection of ENM, fluids, and methods, the different lysosomal simulant fluids did not induce changes of particle morphology, except for small changes in SiO2 and BaSO4 particles most likely due to ion dissolution, reprecipitation, and coalescence between neighboring particles. Based on the current evidence, the particle size by TEM analysis is not a sufficiently sensitive analytical method to deduce the rate of ENM dissolution in physiological media. In summary, we recommend the standardization of ENM dissolution testing by one of the three valid lysosomal simulant fluids with determination of the dissolution rate and halftime by the quantification of ions. This recommendation was established for a continuous flow system but may be relevant as well for static (batch) solubility testing.

Incorporation of itraconazole nano-co-crystals into multiparticulate oral dosage forms

Limited research has been performed on the downstream processing of nano-co-crystal suspensions into solid oral dosage forms. The objectives of this study were to evaluate the impact of three downstream processes (wet granulation, spray granulation and bead layering) on the performance of itraconazole-succinic acid (ITZ-SUC) nano-co-crystal suspension. An optimized ITZ-SUC nano-co-crystal suspension mixed with HPMC E5 was utilized for the downstream processing. The suspension was converted in the solid state either by wet or spray granulation (with microcrystalline cellulose or lactose as substrates) or by layering onto microcrystalline cellulose and sugar beads. The multiparticulate solid dosage forms were characterized by optical microscopy, differential scanning calorimeter (DSC), X-ray powder diffraction (XRPD) and in situ dissolution studies. Spray granulation and bead layering resulted in less particle aggregation, a faster dissolution rate, and higher kinetic solubility when compared to wet granulation. ITZ-SUC nano-co-crystals spray granulated with lactose resulted in higher kinetic solubility profiles compared to microcrystalline cellulose granules. The type of bead core had no impact on the dissolution behavior. A slower dissolution and decreased kinetic solubility were observed with increasing drug loading for sprayed granules when microcrystalline cellulose was used as substrate. All dosage forms were stable under accelerated storage conditions (40 °C/75% RH) when blistered. Nano-co-crystals incorporated in granules were less stable than layered beads under non-blistered condition. Nano-co-crystals layered sugar beads are an interesting alternative to amorphous solid dispersion; a comparable kinetic solubility but a faster drug release were achieved. This study identified bead layering as a superior downstream process approach for incorporating ITZ-SUC nano-co-crystals into an oral solid dosage form without compromising drug dissolution.

Biomass-derived activated carbon as catalyst in the leaching of metals from a copper sulfide concentrate

Chalcopyrite is the resource with the highest amount of Cu content representing around 70–80% of the known reserves in the world. However, chalcopyrite like other copper sulfides, is usually found in deposits with grades around 0.4–0.5% copper. The exploitation of these reserves using traditional flotation methods followed by pyrometallurgical treatment of copper concentrate is at the limit of economic viability. Hydrometallurgical route would be more suitable for treating of these low-graded sulfide ores. However, chalcopyrite is refractory in ferric/sulfuric acid media and shows slow dissolution rates. For this a number of researches were carried out to accelerate the kinetics of leaching by adding pyrite, iron powder, nanosized silica, coal and activated carbon. The main objective of the present work was to study the use of one biomass-derived activated carbon as catalysts in the leaching of copper from chalcopyrite. Sulfuric acid solution of pH 1 with 5 g L−1 of Fe3+ was used as leaching agent. Experiments were performed at 90 °C and 250 rpm, during 48 and 96 h. Concentration of Cu, Zn, As, Sb and Co in the liquid phase was determined in order to evaluate their extraction degree, whereas solid residues were characterized by SEM-EDS and XRD. The presence of biomass-derived activated carbon significantly increased the extraction of copper, decreasing the leaching of arsenic. Furthermore, the use of biomass-derived activated carbon led to lower amounts of crystalline sulfur in the final residue.

Atomistic thermodynamics and kinetics of dicalcium silicate dissolution

Low-temperature cement manufacturing has garnered academic and industrial attention for its low environmental footprints. However, the sluggish hydration kinetics of the resultant cement affects their early-age strength development. This motivates fundamental studies to unravel the mechanistic picture of the dissolution process and discover science-informed pathways to accelerate hydration. Standard atomistic simulations seldomly exceed a microsecond making them impractical to study slow dissolution processes. Here, using rare event sampling techniques, we provide the mechanistic picture of Ca2+ ion dissolution from a kink site on the dicalcium silicate surface. The Ca2+ ion dissolution is comprised of two sequential stages: breaking restraints from the kink sites to form a ledge adatom and detaching from the ledge/terrace adatom sites into the solution. The first and second stages feature free energy barriers of ~63 kJ/mol and ~ 29 kJ/mol respectively, making the first stage the rate-limiting step of the entire Ca2+ dissolution kinetics. Using the reactive flux method, the rate and equilibrium constants for each reaction step are calculated, which yield the Ca2+ ion activity of ~1.03 × 10−5. The diffusion calculations indicate that the surface effects lower the self-diffusion coefficient of Ca2+ ions at the solid-water interface.

Ocean bubbles under high wind conditions – Part 2: Bubble size distributions and implications for models of bubble dynamics

Abstract. Bubbles formed by breaking waves in the open ocean influence many surface processes but are poorly understood. We report here on detailed bubble size distributions measured during the High Wind Speed Gas Exchange Study (HiWinGS) in the North Atlantic, during four separate storms with hourly averaged wind speeds from 10–27 m s−1. The measurements focus on the deeper plumes formed by advection downwards (at 2 m depth and below), rather than the initial surface distributions. Our results suggest that bubbles reaching a depth of 2 m have already evolved to form a heterogeneous but statistically stable population in the top 1–2 m of the ocean. These shallow bubble populations are carried downwards by coherent near-surface circulations; bubble evolution at greater depths is consistent with control by local gas saturation, surfactant coatings and pressure. We find that at 2 m the maximum bubble radius observed has a very weak wind speed dependence and is too small to be explained by simple buoyancy arguments. For void fractions greater than 10−6, bubble size distributions at 2 m can be fitted by a two-slope power law (with slopes of −0.3 for bubbles of radius <80 µm and −4.4 for larger sizes). If normalised by void fraction, these distributions collapse to a very narrow range, implying that the bubble population is relatively stable and the void fraction is determined by bubbles spreading out in space rather than changing their size over time. In regions with these relatively high void fractions we see no evidence for slow bubble dissolution. When void fractions are below 10−6, the peak volume of the bubble size distribution is more variable and can change systematically across a plume at lower wind speeds, tracking the void fraction. Relatively large bubbles (80 µm in radius) are observed to persist for several hours in some cases, following periods of very high wind. Our results suggest that local gas supersaturation around the bubble plume may have a strong influence on bubble lifetime, but significantly, the gas in the bubbles contained in the deep plumes cannot be responsible for this supersaturation. We propose that the supersaturation is predominately controlled by the dissolution of bubbles in the top metre of the ocean, and that this bulk water is then drawn downwards, surrounding the deep bubble plume and influencing its lifetime. In this scenario, oxygen uptake is associated with deep bubble plumes but is not driven directly by them. We suggest that as bubbles move to depths greater than 2 m, sudden collapse may be more significant as a bubble termination mechanism than slow dissolution, especially in regions of high void fraction. Finally, we present a proposal for the processes and timescales which form and control these deeper bubble plumes.

Enriching Oxygen Vacancy Defects via Ag-O-Mn Bonds for Enhanced Diffusion Kinetics of δ-MnO2 in Zinc-Ion Batteries.

Aqueous zinc-ion batteries (ZIBs) have received great attention due to their environmental friendliness and high safety. However, cathode materials with slow diffusion dynamics and dissolution in aqueous electrolytes hindered their further application. To address these issues, in this work, a MnO2-2 cathode doped with 1.12 wt % Ag was prepared, and after 1000 cycles of charge/discharge at 1 A·g-1, the capacity remained at 114 mA·h·g-1 (only 57.7 mA·h·g-1 for pristine MnO2). Cyclic voltammetry (CV), the galvanostatic intermittent titration technique (GITT), the electrochemical quartz crystal microbalance (EQCM) method, and density functional theory (DFT) calculation on pristine δ-MnO2 and MnO2-2 also proved the superior performance of MnO2-2. More investigation disclosed that its superior performance is attributed to the improved diffusion kinetics of the cathode brought by the enriched oxygen vacancy defects due to the formation of Ag-O-Mn bonds. Meanwhile, the kinetic mechanism of the Zn/MnO2-2 cell can be described as a reversible process of the dissolution/precipitation of the ZHS phase and consequent insertion/extraction of Zn2+ and H3O+. Herein, the primary issues of ZIB cathode materials have been addressed and solved to a certain extent. More importantly, such a modification in the design of the advanced manganese-based aqueous ZIB cathode materials can provide further insight and facilitate the development and application of this large-scale energy storage system in the near future.

Ocean bubbles under high wind conditions – Part 1: Bubble distribution and development

Abstract. The bubbles generated by breaking waves are of considerable scientific interest due to their influence on air–sea gas transfer, aerosol production, and upper ocean optics and acoustics. However, a detailed understanding of the processes creating deeper bubble plumes (extending 2–10 m below the ocean surface) and their significance for air–sea gas exchange is still lacking. Here, we present bubble measurements from the HiWinGS expedition in the North Atlantic in 2013, collected during several storms with wind speeds of 10–27 m s−1. A suite of instruments was used to measure bubbles from a self-orienting free-floating spar buoy: a specialised bubble camera, acoustical resonators, and an upward-pointing sonar. The focus in this paper is on bubble void fractions and plume structure. The results are consistent with the presence of a heterogeneous shallow bubble layer occupying the top 1–2 m of the ocean, which is regularly replenished by breaking waves, and deeper plumes which are only formed from the shallow layer at the convergence zones of Langmuir circulation. These advection events are not directly connected to surface breaking. The void fraction distributions at 2 m depth show a sharp cut-off at a void fraction of 10−4.5 even in the highest winds, implying the existence of mechanisms limiting the void fractions close to the surface. Below wind speeds of 16 m s−1 or a wind-wave Reynolds number of RHw=2×106, the probability distribution of void fraction at 2 m depth is very similar in all conditions but increases significantly above either threshold. Void fractions are significantly different during periods of rising and falling winds, but there is no distinction with wave age. There is a complex near-surface flow structure due to Langmuir circulation, Stokes drift, and wind-induced current shear which influences the spatial distribution of bubbles within the top few metres. We do not see evidence for slow bubble dissolution as bubbles are carried downwards, implying that collapse is the more likely termination process. We conclude that the shallow and deeper bubble layers need to be studied simultaneously to link them to the 3D flow patterns in the top few metres of the ocean. Many open questions remain about the extent to which deep bubble plumes contribute to air–sea gas transfer. A companion paper (Czerski et al., 2022) addresses the observed bubble size distributions and the processes responsible for them.

Sedimentary CaCO3 Accumulation in the Deep West Pacific Ocean

Distribution of calcium carbonate (CaCO3) in marine sediment has been studied over the last century, and influence by multiple factors with regard to dissolution and dilution of sedimentary CaCO3 has long been established. There is still lack of quantification on the influence of those factors, so it remains elusive to determine which specific process is driving the down-core variation of CaCO3 content (wtCaCO3%) records. Here, based on a newly compiled CaCO3 data set and a carbonate model, depth-profiles of sedimentary wtCaCO3% from the West Pacific Ocean can be well illustrated, and influence from different factors on their distribution features can be quantified. The deep ocean circulation is found to largely shape the inter-basin disparity in sedimentary wtCaCO3% distribution between the equatorial regions (e.g., the Western Equatorial Pacific Ocean and the Central Pacific Ocean) and the north–west regions (the Philippine Sea and the Northwest Pacific Ocean) in our study region. Moreover, the slow carbonate dissolution rate in the deep Central Pacific Ocean guarantees better accumulation of CaCO3 at depth compared to that in other regions. However, enhanced dilution by non-carbonate materials of sedimentary CaCO3 on a topographic complex can potentially obstruct the dissolution profiles constituted by sedimentary wtCaCO3% in the pelagic ocean. The aforementioned assertion suggests that changes of wtCaCO3% accumulation in marine sediment in the West Pacific Ocean can be used to dictate past changes of the deep ocean circulation (2,500 to 3,000 m) in this area but constraint on the non-carbonate flux, especially on the topographic complex, should be necessary.

Effects of different reduced sulfur forms as electron donors in the start-up process of short-cut sulfur autotrophic denitrification

In this study, two short-cut sulfur autotrophic denitrification (SSADN) reactors were initiated using different reduced sulfur forms as electron donors and their effects on the start-up speed of the SSADN process, NO2−-N accumulation characteristics, and microbial community were investigated. Results revealed that during the same period, due to the relatively slow S0 dissolution rate, the NO2−-N production rate realized by microorganisms in S0-SSADN (NO2−-N production rate (NPR), 174 mg/(L·d)) was significantly slower than S2−-SSADN (NPR, 679 mg/(L·d)). The NO2−-N accumulation efficiency (NAE) was maintained > 80%, which was significantly higher than S2−-SSADN. In the SSADN system using different reduced sulfur forms, the microbial community structure and abundance considerably differed. The main sulfur-oxidizing bacteria (SOB) in S0-SSADN were Sulfurimonas (6.5%) and Thiobacillus (5.3%). The main SOB species in S2−-SSADN was Thiomonas (13.6%). Thermomonas played an important role in the two reactors as an important NO3−-N denitrifying bacteria species.

Soil inorganic carbon sequestration through alkalinity regeneration using biologically induced weathering of rock powder and biochar

Soil inorganic carbon (SIC) accounts for about half of the C reserves worldwide and is considered more stable than soil organic carbon (SOC). However, soil acidification, driven mainly by nitrogen (N) fertilization can accelerate SIC losses, possibly leading to complete loss under continuous and intensive N fertilization. Carbonate-free soils are less fertile, productive, and more prone to erosion. Therefore, minimizing carbonate losses is essential for soil health and climate change mitigation. Rock/mineral residues or powder have been suggested as a cheaper source of amendments to increase soil alkalinity. However, slow mineral dissolution limits its efficient utilization. Soil microorganisms play a vital role in the weathering of rocks and their inoculation with mineral residues can enhance dissolution rates. Biochar is an alternative material for soil amendments, in particular, bone biochar (BBC) contains higher Ca and Mg that can induce even higher alkalinity. This review covers i) the contribution and mechanism of rock residues in alkalinity generation, ii) the role of biochar or BBC to soil alkalinity, and iii) the role of microbial inoculation for accelerating alkalinity generation through enhanced mineral dissolution. We conclude that using rock residues/BBC combined with microbial agents could mitigate soil acidification and SIC losses and also improve agricultural circularity.

Host-guest inclusion complexes of sulfabenzamide with β- and methyl-β-cyclodextrins: Characterization, antioxidant activity and DFT calculation

The inclusion complexation behavior, characterization and binding ability of sulfabenzamide (SBZ) with β-cyclodextrin (β-CD) and methyl-β-cyclodextrin (Mβ-CD) have been investigated both in solution and solid state by different experimental techniques. Sulfabenzamide drug having poor water solubility and slow dissolution. In order to improve its water solubility and thus dissolution, cyclodextrin complexation technique was followed. The spectral shifts revealed that part of aniline ring of SBZ is entrapped in the CD cavity. The association constants were determined by Benesi-Hildebrand plots and spectroscopic studies. The phase solubility studies were carried using two different types of cyclodextrins viz., β, methyl-β cyclodextrins. The phase solubility profiles with all the two cyclodextrins were classified as AL-type, indicating the formation of 1:1 stoichiometric inclusion complexes. Inclusion complexes exhibited higher rates of dissolution than the corresponding physical mixtures and pure drug. Characterization of inclusion complexes was done by solubility studies, in vitro dissolution studies, FTIR, 1HNMR, XRD and SEM studies. We investigated the interaction of the host–guest Mβ-CD/SBZ complex by means of molecular dynamics simulation using a density functional based tight-binding code (DFT).

Structural changes in milk from different species during gastric digestion in piglets

This study investigated the structural and physicochemical changes that occur in milk, a naturally designed complex structured emulsion, during gastric digestion using the bottle-fed piglet as an animal model. The gastric digestions of cow, goat, and sheep milk were compared in male piglets euthanized at different postfeeding times to collect the stomach chyme. The cow and noncow milks separated into curd (aggregated caseins) and liquid (mostly soluble whey) phases in the piglet's stomach. For milk from all the species, the curd remained longer in the stomach because of its slow disintegration, whereas the liquid phase emptied readily. The majority of the fat globules were found to be entrapped within the protein network of the curd. The rate of release of fat globules was strongly dependent on the breakdown of the surrounding protein network of the curd. The consistency of the gastric curds changed as digestion progressed, with goat and sheep milk curds having relatively softer curd consistency and less fused protein networks, especially toward the end of digestion. This might have led to the lower protein and fat retention in the goat and sheep milk curds and relatively faster gastric emptying of these nutrients from goat and sheep milk in comparison to cow milk. This in vivo study provided new and enhanced understanding of the mechanisms of the gastric digestion of milk from different species. It may have implications for developing bioinspired structures for the controlled digestion and delivery of nutrients.

A series of heterometallic 3d-4f polyoxometalates as single-molecule magnets

Three sandwich-like [Ln 2 Fe 2 (B- α -FeW 9 O 34 ) 2 ] 10− clusters (Ln 2 Fe 4 , Ln = Dy( 1 ), Ho( 2 ), and Y( 3 )) were obtained by reacting Na 9 [B- α -SbW 9 O 33 ], Ln 2 O 3 , FeCl 3 •6H 2 O and KH 2 PO 4 . The [B- α -FeW 9 O 34 ] 11− units were formed via the in situ conversion of lacunary polyoxometalates (POM) [B- α -SbW 9 O 33 ] 9− and the Ln 3+ ions were generated from the slow dissolution of Ln 2 O 3 , both of which play important roles in the synthesis of Ln 2 Fe 4 . Ln 2 Fe 4 is the first 3d-4f cluster assembled from d-metal heteroatom-containing POM. The Dy 2 Fe 4 cluster exhibits single-molecule magnet properties with an 80 K energy barrier in an optimal DC field. Cyclic voltammetry tests and controlled-potential coulometry experiments show that the polyoxometalate Fe heteroatom in clusters 1–3 is also electrochemically active. Three polyoxometalate-based 3d-4f clusters featuring single-molecule magnet characteristics were obtained based on the synthetic strategies of conversion of lacunary polyoxometalates and lanthanide ion slow release.

3D printed bioceramic scaffolds: Adjusting pore dimension is beneficial for mandibular bone defects repair.

Bioceramic scaffolds for repairing mandibular bone defects have considerable effects, whereas pore architecture in porous scaffolds on osteogenesis in specific structures is still controversial. Herein 6mol% magnesium-substituted calcium silicate scaffolds were fabricated with similar porosity (∼58%) but different cylindrical pore dimensions (Ø 480, 600, and 720μm) via digital light processing-based three-dimensional (3D) printing technique. The mechanical properties, bioactive ion release, and bio-dissolution of the bioceramic scaffolds were evaluated in vitro, and the facilitation of scaffolds on bone formation was investigated after implanting in vivo. The results showed that as the pore dimension increased, the scaffolds indicated similar surface microstructures, but their compressive strength was enhanced gradually. There was no significant difference in vitro bio-dissolution between the 480 and 600μm groups, whereas the 720μm group showed a much slower dissolution and ion release. Interestingly, the two-dimensional/three-dimensional (2D/3D) micro-CT reconstruction analysis of rabbits' mandibular bone defects model showed that the 600μm group exhibited evidently higher ratio of the newly formed bone volume to total volume (BV/TV) and trabecular number (Tb. N) values and lower ratio of the scaffolds residual volume to total volume (RV/TV) compare to the other two sizes. Furthermore, the histological analysis also revealed a considerably higher new bone ingrowth rate in the 600μm group than the other two groups at 4-12weeks post-implantation. Totally, it is proved from these experimental studies that the DLP-based accurately fabricated calcium (Ca) silicate bioceramic scaffolds with appropriate pore dimensions (i.e., 600μm in pore size) are promising to guide new bone ingrowth and thus accelerate the regeneration and repair of cranial maxillofacial or periodontal bone defects.

The Vanishing Reality of the State: On Hans Blumenberg’s Political Theory

While many interpreters of Hans Blumenberg have searched The Legitimacy of the Modern Age or Work on Myth for hints of a political theory, there is still no in-depth discussion of the only essay published during his lifetime that deals directly with political theory, “The Concept of Reality and the Theory of the State,” which appeared in May 1968. This article reconstructs that essay’s main arguments and contextualizes it in the “historical phenomenology” Blumenberg developed in his middle period. Arguing that we are witnessing a slow dissolution of the state, he suggests that politics is supplanted by rhetoric and the state by supranational structures. Setting apart this historical approach from the anthropological one of his later work, the article argues for a break in Blumenberg’s oeuvre around 1968.