Silymarin-laden PVP-PEG polymeric composite for enhanced aqueous solubility and dissolution rate: Preparation and in vitro characterization

The aim of this work was to develop, optimize and characterize a silymarin-laden polyvinylpyrrolidone(PVP)-polyethylene glycol(PEG) polymeric composite to resolve low aqueous solubility and dissolution rate problem of the drug. A number of silymarin-laden polymeric formulations were fabricated with different quantities of PVP K-30 and PEG 6000 by the solvent-evaporation method. The effect of PVP K-30 and PEG 6000 on the aqueous solubility and dissolution rate was investigated. The optimized formulation and its constituents were characterized using powder X-ray diffraction(PXRD), differential scanning calorimetry(DSC), scanning electron microscopy(SEM) and Fourier transform infrared spectroscopy(FTIR) techniques. Both the PEG 6000 and PVP K-30 positively affected the aqueous solubility and dissolution rate of the drug. In particular, a formulation consisting of silymarin, PVP K-30 and PEG 6000(0.25/1.5/1.5, w/w/w) furnished the highest solubility(24.3972.95 mg/mL) and an excellent dissolution profile( $100% in 40 min). The solubility enhancement with this formulation was $ 1150-fold as compared to plain silymarin powder. Moreover, all the constituents existed in the amorphous state in this silymarin-laden PVP-PEG polymeric composite. Accordingly, this formulation might be a promising tool to administer silymarin with an enhanced effect via the oral route.

Portable and automated analyzer for rapid and high precision in vitro dissolution of drugs

We developed a novel portable and automated dissolution test analyzer for rapid and high precision in vitro dissolution testing of drugs.The analyzer consists of a flow-through-cell drug dissolution system,an automated sequential sampling system,a high-speed capillary electrophoresis(HSCE)system,and a data acquisition system.Combining the high-temporal resolution flow-gating sampling approach with HSCE,which has outstanding advantages of efficient separation and resolution,the analyzer can achieve rapid analysis and exhibits the ability in miniaturization for on-site assessment of different active pharmaceutical ingredients.To integrate the flow-through-cell dissolution system with HSCE,a specially designed flow-gating-injection(FGI)interface was employed.The performance of the analyzer was investigated by analyzing the dissolution of immediate-release drugs including single dose(amoxicillin dispersible tablets)and fixed dose combination(amoxicillin and clavulanate potassium)drug tablets with the high-temporal resolutions of 12 s and 20 s,respectively.The dissolution profiles of different active pharmaceutical ingredients could be simultaneously and automatically monitored with high repeatability and accuracy.The analyzer was successfully utilized for the pharmaceutical quality control and bio-relevant dissolution testing,as well as in vivo-in vitro correlation analysis.Our portable analyzer is miniaturized,convenient and of low-cost,and will provide a valuable tool for dissolution testing in pharmaceutical research and development.

Characteristics and control factors of feldspar dissolution in gravity flow sandstone of Chang 7 Member,Triassic Yanchang Formation,Ordos Basin,NW China

To clarify the formation and distribution of feldspar dissolution pores and predict the distribution of high-quality reservoir in gravity flow sandstone of the 7^(th) member of Triassic Yanchang Formation(Chang 7 Member)in the Ordos Basin,thin sections,scanning electron microscopy,energy spectrum analysis,X-ray diffraction whole rock analysis,and dissolution experiments are employed in this study to investigate the characteristics and control factors of feldspar dissolution pores.The results show that:(1)Three types of diagenetic processes are observed in the feldspar of Chang 7 sandstone in the study area:secondary overgrowth of feldspar,replacement by clay and calcite,and dissolution of detrital feldspar.(2)The feldspar dissolution of Chang 7 tight sandstone is caused by organic acid,and is further affected by the type of feldspar,the degree of early feldspar alteration,and the buffering effect of mica debris on organic acid.(3)Feldspars have varying degrees of dissolution.Potassium feldspar is more susceptible to dissolution than plagioclase.Among potassium feldspar,orthoclase is more soluble than microcline,and unaltered feldspar is more soluble than early kaolinized or sericitized feldspar.(4)The dissolution experiment demonstrated that the presence of mica can hinder the dissolution of feldspar.Mica of the same mass has a significantly stronger capacity to consume organic acids than feldspar.(5)Dissolution pores in feldspar of Chang 7 Member are more abundant in areas with low mica content,and they improve the reservoir physical properties,while in areas with high mica content,the number of feldspar dissolution pores decreases significantly.

Studies on the in Vitro Dissolution of Insoluble Volatile Drug from Su-Anxin Nasal Inhalant and Its Correlation on the Nose Steady Self-Controllable Expiration and Inspiration at Night

In the paper, the in vitro dissolution of borneol in 12 hours from 6 batches of optimized inhalant samples were investigated. As a new dosage form, the in vitro release apparatus of nasal inhalant was invented and a pushing bump was used according to the simulation of the nose expiration and inspiration. Based on the data of r2 in the profile and similar factor f2 from 6 linear release tendencies, a good controlled release and a zero order tendency were observed. It can be suggested that there is a good correlation between the in vitro controlled release and the nose steady self-controllable expiration and inspiration, which will contribute to the trend of insoluble volatile drug controlled release and the effect of quick absorption in nasal pulmonary delivery to cure severe or acute cardiovascular or lung diseases at patients' sleeping, such as angina or breathing obstruction. Also, it was concluded that the prescription composed of insoluble volatile drugs can be prepared to be nasal inhalant from which drugs can be absorbed through nose steady self-controllable inspiration to the lung then into the blood and have a great effectiveness improvement of bioavailability at night timing drug delivery system.

Effect of raw material variability of glipizide on the in vitro dissolution rate and in vivo bioavailability performance: The importance of particle size

The objective of this study was to understand the impact of active pharmaceutical ingredients(API) particle size on a re-developed generic product of glipizide and to improve its formulation so that it exhibits bioequivalent to that of the reference listed drug(RLD). Two commercial batches of APIs(API-1 and API-2) with the same polymorphism and one batch of home-made APIs(API-3) with super-small particle size were used in the present study.The in vitro dissolution profiles of the tested formulations were compared with the RLD in a series of dissolution media. Then, the impact of particle size on in vivo absorption was evaluated in Beagle dogs. Compared with the RLD, formulation A with larger API size showed slower dissolution in p H 6.0 and 7.4 medium, resulting bioinequivalent with the RLD. Conversely, formulation B with smaller API size demonstrated similar in vitro dissolution profiles with the RLD and thus exhibited bioequivalent in the present study. Furthermore, formulation C with super small particle size still exhibited identical oral absorption although rapid dissolution was observed in the tested condition. Herein, it indicated that 2–5 μm might be defined as the "inert size range" of glipizide for ensuring the bioequivalence with the RLD. The results in the present study might help to obtain a better understanding of the variability in raw materials for oral absorption, develop a bioequivalent product and thus post-market quality control.

Study on correlation of computed tomographic classification of a gallstone with its dissolution using methyl tert-butyl ether(MTBE) in vitro

Objective: To access whether CT scans can predict the process and results of MTBE dissolution of gallstones exactly. Methods: Each one of forty-five cases(two stones for each one) were scanned by CT in vitro. Infrared spectrum was performed to analyse qualitatively the stones. The other one of them was dissolved by MTBE. Results: The stones may be divided into five patterns according to CT features. The cholesterol content correlated well with dissolution outcome; only the stones containing more than 40% cholesterol could be dissolved. The lower CT value of a homogeneous stones the faster dissolution of it, and the less residual mass, viceversa. The cholesterol content of the rim of a laminate stone may affect its dissolution course. The rim with less cholesterol content could be penetrated and the center with more cholesterol could be dissolved by MTBE. Conclusion: CT scans can predict the process and outcome of MTBE dissolution of a gallstone exactly.

Ibuprofenβcyclodextrin Inclusion Complex: Preparation, Characterization, PhysicoChemical Properties and In vitro Dissolution Behavior

Inclusion complexation between ibuprofen (IBF) and βcyclodextrin (βCD) was investigated. Phase solubility studies of the complexation suggested the formation of a 1:3 complex and a 2:3 complex between IBF and βCD at room temperature (23℃) and at 37℃ respectively. Solid inclusion complexes were prepared by the homogeneous coprecipitation method. Scanning electron microscopy, differential scanning calorimetry, IR spectroscopy, and Xray diffractometry were used for the characterization and evaluation of the complexes. The solubility and dissolution rate of the complexes formed were found to have improved considerably over that of the physical mixture and the drug alone, indicating that βcyclodextrin played an important role in the solubilization of ibuprofen.

Heterointerface Engineering-Induced Oxygen Defects for the Manganese Dissolution Inhibition in Aqueous Zinc Ion Batteries

Manganese-based material is a prospective cathode material for aqueous zinc ion batteries(ZIBs)by virtue of its high theoretical capacity,high operating voltage,and low price.However,the manganese dissolution during the electrochemical reaction causes its electrochemical cycling stability to be undesirable.In this work,heterointerface engineering-induced oxygen defects are introduced into heterostructure MnO_(2)(δa-MnO_(2))by in situ electrochemical activation to inhibit manganese dissolution for aqueous zinc ion batteries.Meanwhile,the heterointerface between the disordered amorphous and the crystalline MnO_(2)ofδa-MnO_(2)is decisive for the formation of oxygen defects.And the experimental results indicate that the manganese dissolution ofδa-MnO_(2)is considerably inhibited during the charge/discharge cycle.Theoretical analysis indicates that the oxygen defect regulates the electronic and band structure and the Mn-O bonding state of the electrode material,thereby promoting electron transport kinetics as well as inhibiting Mn dissolution.Consequently,the capacity ofδa-MnO_(2)does not degrade after 100 cycles at a current density of 0.5 Ag^(-1)and also 91%capacity retention after 500cycles at 1 Ag^(-1).This study provides a promising insight into the development of high-performance manganese-based cathode materials through a facile and low-cost strategy.

Progress on Transition Metal Ions Dissolution Suppression Strategies in Prussian Blue Analogs for Aqueous Sodium-/Potassium-Ion Batteries

Aqueous sodium-ion batteries(ASIBs)and aqueous potassium-ion batteries(APIBs)present significant potential for large-scale energy storage due to their cost-effectiveness,safety,and environmental compatibility.Nonetheless,the intricate energy storage mechanisms in aqueous electrolytes place stringent require-ments on the host materials.Prussian blue analogs(PBAs),with their open three-dimensional framework and facile synthesis,stand out as leading candidates for aqueous energy storage.However,PBAs possess a swift capacity fade and limited cycle longevity,for their structural integrity is compromised by the pronounced dis-solution of transition metal(TM)ions in the aqueous milieu.This manuscript provides an exhaustive review of the recent advancements concerning PBAs in ASIBs and APIBs.The dissolution mechanisms of TM ions in PBAs,informed by their structural attributes and redox processes,are thoroughly examined.Moreover,this study delves into innovative design tactics to alleviate the dissolution issue of TM ions.In conclusion,the paper consolidates various strategies for suppressing the dissolution of TM ions in PBAs and posits avenues for prospective exploration of high-safety aqueous sodium-/potassium-ion batteries.

Dissolution behavior of Al_(2)O_(3)inclusions into CaO-MgO-SiO_(2)-Al_(2)O_(3)-TiO_(2)system ladle slags

To investigate the dissolution behaviors of Al_(2)O_(3)inclusions in CaO-5wt%MgO-SiO_(2)-30wt%Al_(2)O_(3)-TiO_(2)system ladle slags,confocal scanning laser microscopy was conducted on the slags with different TiO_(2)contents(0-10wt%),and scanning electron microscopy was performed to study the interfacial reaction between Al_(2)O_(3)and this slag system.The results disclose that the dissolution of Al_(2)O_(3)inclusions does not result in the formation of new phases at the boundary between the slag and the inclusions.In TiO_(2)-bearing and TiO_(2)-free ladle slags,there is no difference in the dissolution mechanism of Al_(2)O_(3)inclusions at steelmaking temperatures.Boundary layer diffusion is found as the controlling step of the dissolution of Al_(2)O_(3),and the diffusion coefficient is in the range of 4.18×10^(-10)to 2.18×10^(-9)m^(2)/s at 1450-1500℃.Compared with the solubility of Al_(2)O_(3)in the slags,slag viscosity and temperature play a more profound role in the dissolution of Al_(2)O_(3)inclusions.A lower viscosity and a lower melting point of the slags are beneficial for the dissolution.Suitable addition of TiO_(2)(e.g.,5wt%)in ladle slags can enhance the dissolution of Al_(2)O_(3)inclusions because of the low viscosity and melting point of the slags,while excessive addition of TiO_(2)(e.g.,10wt%)shows the opposite trend.

Zn Dissolution-Passivation Behavior with ZnO Formation via In Situ Characterizations

In this study,ZnO formation during the dissolution-passivation process of Zn anodes is observed via in situ Raman and optical characterization.The Zn passivation during galvanostatic anodization merely follows the dissolution-precipitation model,whereas that of potentiodynamic polarization exhibits different behaviors in different potential ranges.Initially,the Zn electrode is gradually covered by a ZnO precipitation film and then undergoes solid-state oxidation at~255 mV.The starting point of solid-state oxidation is well indicated by the abrupt current drop and yellow coloration of the electrode surface.During the pseudo passivation,an intense current oscillation is observed.Further,blink-like color changes between yellow and dark blue are revealed for the first time,implying that the oscillation is caused by the dynamic adsorption and desorption of OH groups.The as-formed ZnOs then experience a dissolution-reformation evolution,during which the crystallinity of the primary ZnO film is improved but the solid-state-formed ZnO layer becomes rich in oxygen vacancies.Eventually,oxide densification is realized,contributing to the Zn passivation.This study provides new insights into the Zn dissolution-passivation behavior,which is critical for the future optimization of Zn batteries.

Effect of Slag Basicity on Alumina Dissolution and Diffusivity:A High-temperature Confocal Laser Scanning Microscopy Study

Alumina is one of the crucial and extensively utilized refractory components.As the refractory wear due to dissolution at elevated temperatures during operation is a major threat to refractory lifespan,quantifying dissolution is important for developing cost-effective and resource-efficient refractories.This study investigated the dissolution of alumina particles in two silicate and one calcium aluminate slags at 1450,1500,and 1550°C using high-temperature confocal laser scanning microscopy(HT-CLSM).Dissolution was quantified in terms of diffusivity,with all influencing factors,including Stefan flow and bath movement,incorporated into the determination process.The trends observed in total dissolution time and diffusivity in three slags at three experimental temperatures could not be explained solely on the basis of slag basicity.Two parameters,considering the influencing factors,were introduced to explain these trends.Furthermore,the linear trend observed in Arrhenius plots of diffusivities supports the diffusivity results.Additionally,good agreement between the diffusivities of alumina in one silicate slag obtained via CLSM and rotating finger test investigations verified the reliability of the results.

The Identification of Phenylalanine Ammonia-Lyase(PAL)Genes from Pinus yunnanensis and an Analysis of Enzyme Activity in vitro

Phenylalanine ammonia lyase(PAL)is the rate-limiting and pivotal enzyme of the general phenylpropanoid path-way,but few reports have been found on PAL genes in Pinus yunnanensis.In the present study,three PAL genes were cloned and identified from P.yunnanensis seedlings for thefirst time,namely,PyPAL-1,PyPAL-2,and PyPAL-3.Our results indicated that the open-reading frames of PyPAL genes were 2184,2157,and 2385 bp.Phylogenetic tree analysis revealed that PyPALs have high homology with other known PAL genes in other plants.In vitro enzymatic analysis showed that all three PyPAL recombinant proteins could catalyze the deamination of L-phenylalanine to form trans-cinnamic acid,but only PAL1 and PAL2 can catalyze the conversion of L-tyrosine toρ-coumaric acid.Three PyPAL genes were expressed in different tissues in 1-year-old P.yunnanensis,and such genes had different expression patterns.This study lays a foundation for further understanding of the biosynthesis of secondary metabolites in P.yunnanensis.

Changes in Polyphenols and Antioxidant Activities of Yingshan Yunwu Tea during Digestion in Vitro

[Objectives]To explore the change rule of polyphenol content and antioxidant activity of coarse old leaves of Yingshan Yunwu Tea in the process of human digestion.[Methods]The coarse and old leaves of Yunwu tea in Yingshan,Huanggang,Hubei Province were selected as the research object,and their digestion in vitro was simulated.The total polyphenol content was determined by Folin-phenol reagent colorimetric method,and the DPPH radical scavenging activity and total antioxidant activity were determined.[Results]After simulated gastrointestinal digestion in vitro,the polyphenol content and antioxidant activity of coarse old leaf tea soup showed a downward trend.After gastrointestinal digestion,the polyphenol content in tea infusion separately decreased by 31.8%and 8.5%;the scavenging rate of DPPH free radical was 97%before digestion,decreased to 92%after gastric digestion and 65%after intestinal digestion,which decreased by 5%and 27%,respectively;after gastrointestinal digestion,the total antioxidant capacity of tea soup decreased by 4.7%and 3.1%,respectively.[Conclusions]This study provided a reference for the development and application of coarse old leaves of Yingshan Yunwu tea,and provided a reference for the nutritional value evaluation and comprehensive utilization of coarse old leaves,so as to make the best use of coarse tea leaves and reduce the waste of resources.

Later-Life Marital Dissolution in Italy:An Emerging Phenomenon?

The phenomenon of marital dissolution in later life,also referred to as“gray divorce”,is described on the rise in contemporary Western societies.This article contributes to the study of marriage breakdown in older age,with a specific focus on Italian society.First,the temporal trends of this phenomenon are reconstructed using official statistics.The data reveal that,although still relatively rare,the dissolution of marriage in later life is expanding in Italy.The analysis of the period from 1974 to 2015 indicates a rise in the average age at separation,a higher percentage of spouses over 50 years on the total number of couples obtaining legal separation,and an increase in the proportion of Italian spouses separating after many years of marriage.Furthermore,data from the national survey“Family and Social Subjects”,conducted in 2016 by the Italian National Institute of Statistics,are utilized to explore the relationship between specific traits of those who separated and their tendency to dissolve marriages before or after the age of 50.The data suggest that individuals with characteristics such as lower educational attainment,residence in the South and Islands,and adherence to more traditional family models are more likely to experience separation in later life.

Role of Polyethylene Glycol and Silica for Dissolution Enhancement of Cefuroxime Axetil: In-Vitro Performance Evaluation and Characterization

Cefuroxime Axetil (CA) a widely used cephalosporin antibiotic displays low aqueous solubility and high membrane penetrability. This results in its solubility driven variable and/or low oral bioavailability and therapeutic efficacy as a major drawback. Thus, most of the goal of our study was to increase the solubility as well as dissolution rate of CA using the simple and cost-effective solid dispersion (SD) method. At first, the SD formulations of CA were prepared at various weight ratios of Carplex-67 and PEG-4000 by solvent evaporation technique. These new formulations were then subjected to an in-vitro drug release performance study and tested for physicochemical characterization to distinguish the thermal behavior, crystallinity, interactions phenomena, and surface morphology. Among the formulated Cefuroxime Axetil Solid Dispersion (CSD), CSD-8 which contained CA, Carplex-67, and PEG-4000 at the weight ratio 1:3:2, respectively showed the most significant (p in-vitro dissolution in water, Gastric Simulated Fluid (GSF), and Intestinal Simulated Fluid (ISF). This study also showed a significant (p < 0.001) increase in drug release compared to the marketed product. Therefore, it is supposed to be a promising alternative to conventional antimicrobial therapy.

Oxygen tension modulates cell function in an in vitro three-dimensional glioblastoma tumor model

Hypoxia is a typical feature of the tumor microenvironment,one of the most critical factors affecting cell behavior and tumor progression.However,the lack of tumor models able to precisely emulate natural brain tumor tissue has impeded the study of the effects of hypoxia on the progression and growth of tumor cells.This study reports a three-dimensional(3D)brain tumor model obtained by encapsulating U87MG(U87)cells in a hydrogel containing type I collagen.It also documents the effect of various oxygen concentrations(1%,7%,and 21%)in the culture environment on U87 cell morphology,proliferation,viability,cell cycle,apoptosis rate,and migration.Finally,it compares two-dimensional(2D)and 3D cultures.For comparison purposes,cells cultured in flat culture dishes were used as the control(2D model).Cells cultured in the 3D model proliferated more slowly but had a higher apoptosis rate and proportion of cells in the resting phase(G0 phase)/gap I phase(G1 phase)than those cultured in the 2D model.Besides,the two models yielded significantly different cell morphologies.Finally,hypoxia(e.g.,1%O2)affected cell morphology,slowed cell growth,reduced cell viability,and increased the apoptosis rate in the 3D model.These results indicate that the constructed 3D model is effective for investigating the effects of biological and chemical factors on cell morphology and function,and can be more representative of the tumor microenvironment than 2D culture systems.The developed 3D glioblastoma tumor model is equally applicable to other studies in pharmacology and pathology.

Corrosion and in vitro cytocompatibility investigation on the designed Mg-Zn-Ag metallic glasses for biomedical application

In the present work,seven Mg-Zn-Ag alloys with the nominal composition of Mg_(96-x)Zn_(x)Ag_(4)(x=17,20,23,26,29,32,35 in at.%)were prepared by induction melting and single-roller melt-spinning.The X-ray diffraction(XRD)analyses indicate the metallic glasses with three composition of Mg_(73)Zn_(23)Ag_(4),Mg_(70)Zn_(26)Ag_(4),and Mg_(67)Zn_(29)Ag_(4)were obtained successfully.The differential scanning calorimetry(DSC)measurement was used to obtain the characteristic temperature of Mg-Zn-Ag metallic glasses for the glass-forming ability analysis.The maximum glass transition temperature(Trg)was found to be 0.525 with a composition close to Mg_(67)Zn_(29)Ag_(4),which results in the best glass-forming ability.Moreover,the immersion test in simulated body fluid(SBF)demonstrate the relative homogeneous corrosion behavior of the Mg-Zn-Ag metallic glasses.The corrosion rate of Mg-Zn-Ag metallic glasses in SBF solution decreases with the increase of Zn content.The sample Mg_(67)Zn_(29)Ag_(4)has the lowest corrosion rate of 0.19mm/yr,which could meet the clinical application requirement well.The in vitro cell experiments show that the Madin-Darby canine kidney(MDCK)cells cultured in sample Mg_(67)Zn_(29)Ag_(4)and its extraction medium have higher activity.However,the Mg-Zn-Ag metallic glasses exhibit obvious inhibitory effect on human rhabdomyosarcoma(RD)tumor cells.The present investigations on the glass-forming ability,corrosion behavior,cytocompatibility and tumor inhibition function of the Mg-Zn-Ag based metallic glass could reveal their biomedical application possibility.

Effect of wall-disruption on nutrient composition and in vitro digestion of camellia and lotus bee pollens

The nutrient digestion,absorption and biological activity of bee pollen may be limited due to the complex pollen wall.Here,the effect of superfine grinding technology on the release of nutrients from bee pollen were investigated,and their antioxidant activities and in vitro digestion were explored in this study.Results showed that the content of nutrients in bee pollen increased after wall disruption.Among them,fat content increased by 22.55%-8.31%,protein content increased by 0.54%-4.91%,starch content increased by 36.31%-48.64%,soluble sugar content increased by 20.57%-29.67%,total phenolic acid content increased by 11.73%-86.98%and total flavonoids content increased by 14.29%-24.79%.At the same time,the antioxidant activity increased by 14.84%-46.00%.Furthermore,the active components such as phenolic compounds in the wall-disruption bee pollen were more readily to be released during the in vitro digestion,and easier to be absorbed because of their higher bioaccessibility.Antioxidant activities during in vitro digestion were also improved in walldisruption bee pollen.These findings provide evidence that bee pollen wall disruption was suggested,thus,it is more conducive to exerting the value of bee pollen in functional foods.

Simulation and fabrication of in vitro microfluidic microelectrode array chip for patterned culture and electrophysiological detection of neurons

To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip was designed based on the specific structure of neurons and the requirements for detection and modulation.Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels.By employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated successfully.Primary hippocampal neurons were cultured on the chip,forming a well-defined neural network.Spontaneous electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array.This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.