Dissolution Conditions Research Articles

Optimizing dissolution and dispersion conditions for metal and metal oxide nanoparticles used as antimicrobial agents

Optimizing dissolution and dispersion conditions for metal and metal oxide nanoparticles used as antimicrobial agents

Impact of sink conditions on drug release behavior of controlled-release formulations

Developing a controlled release (CR) formulations is a complex and iterative process, often requiring preclinical or clinical studies to establish in vitro-in vivo correlations. This can be particularly challenging for poorly soluble drugs due to the non-sink conditions encountered in vitro. Although compendial dissolution methods (e.g., USP II, IV) have historically been used to understand the dissolution performance of CR formulations, there is increasing interest in more physiologically relevant experimental techniques to improve the predictive ability. In this study, traditional USP apparatus as well as the biorelevant absorptive dissolution apparatus were employed to understand the impact of apparatus type and sink condition on the release mechanisms of CR formulations and in turn evaluate the application of absorptive dissolution apparatus for dissolution testing of CR formulations. Release mechanisms were further analyzed using the Peppas equations, providing additional mechanistic insights. The release behavior showed a strong dependence on sink conditions for drugs with low intrinsic solubility, while highly soluble drugs were unaffected by dissolution conditions. Interestingly, the dissolution mechanism was found to be independent of the apparatus type. The study clearly underscores the importance of considering the sink conditions in developing more predictive and biorelevant dissolution testing methods for CR formulations. Furthermore, the study highlights the potential impact on the sink and resultant differences in the drug release mechanisms as a function of the dose.

Molecular-properties based formulation guidance tree for amorphous and supersaturable mesoporous silica preparations of poorly soluble compounds

A huge majority of new chemical entities (NCEs) advancing through the drug discovery pipeline often have poor aqueous solubility. This requires formulation scientists to search for solubility enhancement strategies, within the constraints of time and material. To address these challenges, a strategic platform formulation is often required for a rapid compound screening to enable early exploratory PK and toxicology studies. Through this work, we present an option of a material-sparing, high yielding and solubility-enabling amorphous API and HPMCAS-L co-loaded mesoporous silica-based formulation. The usability of this platform formation strategy was assessed for a physico-chemically diverse set of eleven compounds. The formulation approach was successful in stabilizing the model compounds mesoporous silica. Additionally, through the presence of HPMCAS-L, the precipitation risk in supersaturable aqueous environment was significantly reduced. Finally, this manuscript provides fundamental, computational and experimental molecular-properties based formulation guidance tree to a priori gauge the (1) possibility of generating solid-state stable amorphous formulations and (2) sustaining in vitro supersaturation in extreme non-sink dissolution conditions. This unique and conceptual formulation guidance tree is believed to be extremely beneficial to drug discovery formulators to triage NCEs and streamline solubility-enabling formulation efforts.

Application of shadowgraph imaging (SGI) particle characterisation data to interpret the impact of varying test conditions on powder dissolution and to develop an automated agglomeration identification method (AIM) in the USP flow-through apparatus

The aims of this work were 1) to explore the application of shadowgraph imaging (SGI) as a real time monitoring tool to characterize ibuprofen particle behaviour during dissolution testing under various conditions in the USP 4 flow-through apparatus and 2) to investigate the potential to develop an SGI-based automated agglomeration identification method (AIM) for real time agglomerate detection during dissolution testing. The effect of surfactant addition, changes in the drug mass and flow rate, the use of sieved and un-sieved powder fractions, and the use of different drug crystal habits were investigated. Videos at every sampling time point during dissolution were taken and analysed by SGI. The AIM was developed to characterize agglomerates based on two criteria – size and solidity. All detections were confirmed by manual video observation and a reference agglomerate data set. The method was validated under new dissolution conditions with un-sieved particles. Characterisation of particle dispersion behaviour by SGI enabled interpretation of the impact of dissolution test conditions. Higher numbers of early detections reflected greater dissolution rates with increased surfactant concentration, using sieved fraction or plate-shaped crystals, but was impacted by drug mass tested. An AIM was successfully developed and applied to detect agglomerates during dissolution, suggesting potential, with appropriate method development, for application in quality control.

A Rapid, Sensitive, and High-throughput Method for the Simultaneous Determination of Antihypertensive Drug Combinations in Dog Plasma by UHPLC-MS/MS: The Assessment of Predicable Bioequivalence of In-vitro Dissolution Condition.

Essential hypertension is a common clinical disease and a risk factor for cardiovascular and cerebrovascular diseases. Olmesartan medoxomil, amlodipine, and hydrochlorothiazide are commonly used antihypertensive drugs. The aim of this study was to establish a robust UPLC-MS/MS method for the simultaneous determination of olmesartan medoxomil, amlodipine, and hydrochlorothiazide in dog plasma. At the same time, the in vivo and in vitro release studies were conducted, and a preliminary in vitro-in vivo correlation (IVIVC) evaluation was performed. The bioequivalence experiment was conducted with a double-crossed design. Three major components were extracted and analyzed by UHPLC-MS/MS. With the MRM scan, olmesartan and amlodipine were quantified by fragment conversion (m/z 447.10→190.10) and (m/z 408.95→294.00) under positive ESI mode, while hydrochlorothiazide was quantified with fragment conversion (m/z 295.90→268.90) under negative ESI mode. The in vitro release studies were performed using a USP paddle, and the dissolution medium was chosen from pH 6.0 to pH 6.8 according to the BCS classification of compounds. The IVIVC was calculated using the Wagner-Nelson equation. The linear ranges of olmesartan, amlodipine, and hydrochlorothiazide in the plasma were 5.0-2500, 0.1-50, and 3.0-1500 ng/mL, respectively. All accuracies were within 3.8% of the target values, and the findings revealed that intra-day and inter-day accuracies were less than 12.1%. Moreover, the recoveries exceeded 88.3%, the matrix effect tests were positive, and the stability tests were positive. With the establishment of correlation, the distinguishable dissolution condition (pH 6.8) was selected as the predictable condition. The established method was suitable for the preclinical pharmacokinetic study of tripartite drugs with strong specificity and high sensitivity. Through the evaluation of IVIVC, the connection between in vivo and in vitro drug testing was initially established.

Leaching of Neodymium From Hard Disk Drive Magnet Waste Using Citric Acid‐ Design of Experiments and Optimization

AbstractNeodymium magnet waste recycling and precious metal recovery have drawn a lot of researchers’ attention because of their vital role in contemporary technology. In this work, the potential of citric acid for the leaching of neodymium from hard disk drive waste magnets has been examined using statistical approaches like full factorial design(FFD) and central composite design (CCD).The variables have been screened and conditions are optimized to obtain higher leaching. The polynomial quadratic Model proves effective to predict optimized conditions for neodymium leaching. Leachant concentration and temperature were screened as the most effective factors. Optimization conditions for the leaching process were achieved through central composite design, revealing that 2 mol/L citric acid and a temperature of 333 K provide the ideal conditions for the complete dissolution of neodymium. This extensive study contributes to sustainable materials management and resource conservation by illuminating the effective recovery of important metals from neodymium magnets.

Establishment of Dissolution Test Method for Multi-Components in Traditional Chinese Medicine Preparations Based on In Vitro-In Vivo Correlation.

In this study, a multi-component integrated dissolution evaluation system of Yuanhu Zhitong tablets (YZTs) was established based on in vitro and in vivo correlation (IVIVC). The dissolution tests of five quality markers (Q-markers), including tetrahydropalmatine, α-allocryptopine, protopine, corydaline, and byakangelicin, in YZTs were conducted under different dissolution conditions, and pharmacokinetic studies were performed in beagle dogs to construct a correlation model using numerical deconvolution. The data of the five ingredients were integrated in vitro and in vivo according to the biopharmaceutical classification system (BCS) to establish an IVIVC integrating multiple Q-markers. The dissolution media with the best correlation of components were obtained and validated. The results showed that all five components were classified as BCS I compounds, and α-allocryptopine, byakangelicin, tetrahydropalmatine, and corydaline showed good correlation in the paddle method, 75 rpm, with dissolution media of artificial gastric fluid, acetate buffer, acetate buffer and 0.1 M HCl, respectively. Protopine showed good correlation in the paddle method, 100 rpm, with dissolution media of 0.1 M HCl. The integrated BCS I Q-markers showed the best correlation in the medium of acetate buffer. The multi-component integrated dissolution evaluation system established in this experiment accurately predicted the pharmacokinetic data of YZTs by verifying the media, which can be used for the quality control of YZTs. The present study provides an effective and promising strategy for the dissolution evaluation for traditional Chinese medicine preparations.

Dissolution of porous media with disordered geometry

Dissolution of porous media is a crucial phenomenon in various application fields, necessitating a comprehensive understanding of the underlying mechanisms in order to accurately predict and control the evolution of the media. In our study, we investigate the impact of geometric disorder and injection rates using a combination of experimental and theoretical approaches. To capture more detailed information about dissolution, we employed a high-resolution camera to accurately record the dissolution process observed in our experiments. We identified several dissolution patterns and discussed how both the injection rate and geometric disorder influence these patterns. In addition, we analyzed the evolution of porosity, dissolution rates, and flow velocity using image processing technology. We found a complex, non-linear relationship between the evolution of the media and the flow dynamics, indicating that both injection rate and geometric disorder are crucial factors in the dissolution process. To improve our ability to predict the evolution of porous media under dissolution conditions, we developed a model that incorporates the coupling effects of injection rate and degree of disorder. Our models have successfully provided insights into the interconnected roles of injection rate and geometric disorder in dissolution processes, which can be valuable for the exploitation of subsurface resources.

Establishing Virtual Bioequivalence and Clinically Relevant Specifications for Omeprazole Enteric-Coated Capsules by Incorporating Dissolution Data in PBPK Modeling.

Currently, Biopharmaceutics Classification System (BCS) classes I and III are the only biological exemptions of immediate-release solid oral dosage forms eligible for regulatory approval. However, through virtual bioequivalence (VBE) studies, BCS class II drugs may qualify for biological exemptions if reliable and validated modeling is used. Here, we sought to establish physiologically based pharmacokinetic (PBPK) models, in vitro-in vivo relationship (IVIVR), and VBE models for enteric-coated omeprazole capsules, to establish a clinically-relevant dissolution specification (CRDS) for screening BE and non-BE batches, and to ultimately develop evaluation criteria for generic omeprazole enteric-coated capsules. To establish omeprazole's IVIVR based on the PBPK model, we explored its in vitro dissolution conditions and then combined in vitro dissolution profile studies with in vivo clinical trials. The predicted omeprazole pharmacokinetics (PK) profiles and parameters closely matched the observed PK data. Based on the VBE results, the bioequivalence study of omeprazole enteric-coated capsules required at least 48 healthy Chinese subjects. Based on the CRDS, the capsules' in vitro dissolution should not be < 28%-54%, < 52%, or < 80% after two, three, and six hours, respectively. Failure to meet these dissolution criteria may result in non-bioequivalence. Here, PBPK modeling and IVIVR methods were used to bridge the in vitro dissolution of the drug with in vivo PK to establish the BE safety space of omeprazole enteric-coated capsules. The strategy used in this study can be applied in BE studies of other BCS II generics to obtain biological exemptions and accelerate drug development.

Marriage without Love, Love outside Marriage: A Woman in the Eighteenth-century Noble Family

This article refers to a set of documents revealing the relations within the noble family of the Ural industrialist A. F. Turchaninov and one of his daughters, Natalia Koltovskaya, in the eighteenth century. The author considers general problems of the private life of people of a privileged Russian class, namely, marital relations, possibilities, and conditions of dissolution of marriage, the position of women in the family and their rights, and the attitude to extramarital affairs in secular society. The article examines the reasons for the emergence and development of a provincial woman’s sense of independence and inner freedom, the origins of her rebellion against patriarchal family structures, for the right to decide for herself, and the extent to which such manifestations of “freedom” could be considered typical of Russia at that time, or whether they should be considered an exception to the general norm of behaviour. The story of N. A. Koltovskaya’s escape from her family, her relations with Emperor Paul I and Senator G. R. Derzhavin, shows the conformism of the supreme power, which manifested itself, on the one hand, in the awareness of the latter of the importance of its role in protecting the family and the moral foundations of the upper class, and, on the other hand, in the possibility of the upper class to take advantage of the opportunities offered by the situation and, if necessary, of circumventing the existing rules of law, of influencing government bodies (the Senate) in one’s own interests and, in general, in the interference of the supreme power in the family life of its subjects. The appendix to the article contains four documents: two “women’s” letters – one from the mother to Catherine II and the other from the daughter to Paul I, as well as letters from her lover (translated from French) and her husband.

The ultrasound leaching kinetics of copper in the H2SO4 dissolution process

ABSTRACT The atmospheric immersion copper dissolution method, commonly employed in the current copper foil production process, is confronted with challenges such as low oxidation ability and the formation of passivation layers on the copper surface. These issues result in slow copper dissolution rates, significantly restricting copper foil production. To overcome this limitation, ultrasound is used to improve the copper dissolution process. The impact of ultrasound on the rate and kinetics of copper dissolution in a sulfuric acid solution was studied. Various factors, including ultrasound power, temperature, Cu2+ concentration, sulfuric acid concentration, and air flow rate, were analysed to assess their influence on the rate of copper dissolution. The optimised dissolution conditions were determined to be 30 g/L Cu2+, 120 g/L sulfuric acid, 300 mL/min air flow, 60°C, and 300 W ultrasonic power. The copper dissolution rate is 1.96 times higher when ultrasound is applied compared to conventional conditions. According to the kinetic study, ultrasound reduced the apparent activation energy from 61.12 kJ/mol to 46.44 kJ/mol, significantly lowering the potential barrier for copper dissolution. This study provides valuable insights for accelerating the dissolution process of copper using ultrasound-assisted technology.

Kinetic Model of Fluorescein Release through Bioprinted Polylactic Acid Membrane.

Polylactic acid (PLA)-based cylindrical membranes for the controlled release of fluorescein sodium salt (FS) were prepared by bioprinting on systems with an initial FS concentration of 0.003763 gdm-3 and 37.63 gdm-3, and the drug release process was monitored in a bath at 37 °C. Photographs, acquired at regular intervals during the process, revealed marked osmotic swelling of the polymer. Osmotic swelling consists in the enlargement of the polymer structure and due to the influx of water molecules across the membrane. The cylindrical PLA membrane starts to significantly swell once a certain threshold range is crossed. Important amounts of FS can dissolve under these radically changed circumstances, and the dissolved FS molecules are mobile enough to diffuse out of the cylinder, thus allowing drug release. As a matter of fact, in this investigation, we ascertained that polymer swelling promotes the mass transport phenomenon by altering the conditions for drug dissolution and diffusion, hence facilitating FS release after a specific lag time. Furthermore, in order to compare the release kinetics, the half-release time, t0.5, was taken into consideration. The data of this study evidence that, while increasing the initial concentration of FS by three orders of magnitude, the time parameter, t0.5, is only reduced by 5/6. In addition, the yield of the release process is drastically reduced due to the strong aggregation ability of the dye. Finally, it is demonstrated that a compressed exponential kinetic model fits the experimental data well despite the varying physical conditions.

Insights into the dissolution of cellulose in lithium bromide solution

Lithium bromide molten salt hydrate (∼62 wt% aqueous solution of LiBr) can dissolve cellulose, but the cellulose dissolution mechanisms are not fully understood. This study revisited cellulose dissolution in the LiBr solution and aimed to provide new insights into the dissolution mechanisms. The collected evidence suggested that cellulose dissolution in the LiBr solution is primarily attributed to the disruption of intermolecular H-bonds of cellulose by the ion-dipole coordination between hydrated Li+ and cellulose hydroxy. The coordination between Li+ and cellulose was verified by 7Li NMR and simultaneous DSC-TGA analysis. The observations in this study also suggest that polarizable, large-size, and low-electronegativity Br– plays a synergetic and supplementary role in the dissolution of cellulose. In addition, the dissolution of cellulose in the LiBr solution is greatly dependent on dissolution conditions (LiBr concentration, temperature, pH, and cellulose loading) and cellulose properties (particle size and degree of polymerization).

Optimising Recycling Processes for Polyimine-Based Vitrimer Carbon Fibre-Reinforced Composites: A Comparative Study on Reinforcement Recovery and Material Properties.

We investigated the recycling process of carbon fibre-reinforced polyimine vitrimer composites and compared composites made from virgin and recycled fibres. The vitrimer matrix consisted of a two-component polyimine-type vitrimer system, and as reinforcing materials, we used nonwoven felt and unidirectional carbon fibre. Various diethylenetriamine (DETA) and xylene solvent ratios were examined to find the optimal dissolution conditions. The 20:80 DETA-xylene ratio provided efficient dissolution, and the elevated temperature (80 °C) significantly accelerated the process. Scaling up to larger composite structures was demonstrated. Scanning electron microscopy (SEM) confirmed effective matrix removal, with minimal residue on carbon fibre surfaces and good adhesion in recycled composites. The recycled nonwoven composite exhibited a decreased glass transition temperature due to the residual solvents in the matrix, while the UD composite showed a slight increase. Dynamic mechanical analysis on the recycled composite showed an increased storage modulus for nonwoven composites at room temperature and greater resistance to deformation at elevated temperatures for the UD composites. Interlaminar shear tests indicated slightly reduced adhesion strength in the reprocessed composites. Overall, this study demonstrates the feasibility of recycling vitrimer composites, emphasising the need for further optimisation to ensure environmental and economic sustainability while mitigating residual solvent and matrix effects.

Structural Characterization of 6-Halo-6-Deoxycelluloses by Direct-Dissolution Solution-State NMR Spectroscopy.

Regioselective modifications of cellulose using activated cellulose derivatives such as 6-halo-6-deoxycelluloses provide a convenient approach for developing sustainable products with properties tailored to specific applications. However, maintaining precise regiochemical control of substituent distribution in 6-halo-6-deoxycelluloses is challenging due to their insolubility in most common solvents and the resulting difficulties in precise structure elucidation by modern instrumental analytical techniques. Herein, an accessible NMR-based approach toward detailed characterization of 6-halo-6-deoxycelluloses, including the determination of the degrees of substitution at carbon 6 (DS6), is presented. It is shown that the direct-dissolution cellulose solvent, tetrabutylphosphonium acetate:DMSO-d6, converts 6-halo-6-deoxycelluloses to 6-monoacetylcellulose, enabling in situ solution-state NMR measurements. Arange of 1D and 2D NMR experiments is used to demonstrate the quantitivity of the conversion and provide optimum dissolution conditions. In comparison with other NMR-based derivatization protocols for elucidating the structure of 6-halo-6-deoxycelluloses, the presented approach offers major advantages in terms of accuracy, speed, and simplicity of analysis, and minimal requirements for reagents or NMR instrumentation.

Leaching of Nickel and Cobalt from a Mixed Nickel-Cobalt Hydroxide Precipitate Using Organic Acids

Nickel (Ni) and cobalt (Co) are strategic metals that have found applications in a wide range of metallurgical and industrial uses. In this study, the dissolution of a mixed nickel–cobalt hydroxide precipitate using organic acids (citric, oxalic, and malic acid) was investigated. Citric acid was found to be the best leaching agent yielding the following dissolution rates: 91.2% Ni, 86.8% Co, and 90.8% Mn. Oxalic acid resulted in low dissolution, which is likely due to the formation of insoluble metal oxalates. The impact of acid concentration, leaching time, and temperature on metal dissolution was systematically examined. The optimal dissolution conditions were identified as 0.5 M citric acid at 30 °C for 30 min, utilizing a 1/20 solid/liquid ratio and a stirring speed of 400 revolutions per minute (rpm). The attempt to use oxidants, such as potassium permanganate (KMnO4) and hydrogen peroxide (H2O2), to achieve selective dissolution in an organic acid environment was not successful, which was different from that in the sulfuric acid case. As for the leaching kinetics in the organic acids, it seems that the leaching of Ni correlates with the Shrinking Core Model, specifically regarding porous-layer diffusion control. Based on the experimental results, the activation energy for the leaching of Ni was estimated to be 3.1 kJ/mol.

General Local Reactive Boundary Condition for Dissolution and Precipitation Using the Lattice Boltzmann Method

AbstractA general and local reactive boundary condition (RBC) for studying first‐order equilibrium reactions using the lattice Boltzmann method is presented. Its main characteristics are accurate reproduction of wall diffusion, invariance to the wall and grid orientation, and absence of nonphysical artifacts. The scheme is successfully tested for different benchmark cases considering diffusion, advection, and reactions of fluids at solid‐liquid interfaces. Unlike other comparable RBCs from the literature, the novel scheme is valid for a large range of Péclet and Damköhler numbers, and shows realistic pattern formation during precipitation. In addition, quantitative results are in good accordance with analytical solutions and values from literature. Combining the new RBC with the rest fraction method, Péclet‐Reynolds ratios of up to 1,000 can be achieved. Overall, the novel RBC accurately models first‐order reactions, is applicable for complex geometries, and allows efficiently simulating dissolution and precipitation phenomena in fluids at the pore scale.

Burst Release from In Situ Forming PLGA-Based Implants: 12 Effectors and Ways of Correction.

This systematic review examines the reasons for the phenomenon of active ingredient "burst" release, which is a major drawback of PLGA-based in situ formed implants, and the likely ways to correct this phenomenon to improve the quality of in situ formed implants with a poly(DL-lactide-co-glycolide) matrix. Actual and relevant publications in PubMed and Google Scholar databases were studied. The concept of the review was based on the theory developed during literature analysis of 12 effectors on burst release from in situ forming implants based on PLGA. Only those studies that sufficiently fully disclosed one or another component of the theory were included. The analysis resulted in development of a systematic approach called the "12 Factor System", which considers various constant and variable, endogenous and exogenous factors that can influence the nature of 'burst release' of active ingredients from PLGA polymer-based in situ formed implants. These factors include matrix porosity, polymer swelling, LA:GA ratio, PLGA end groups, polymer molecular weight, active ingredient structure, polymer concentration, polymer loading with active ingredients, polymer combination, use of co-solvents, addition of excipients, and change of dissolution conditions. This review also considered different types of kinetics of active ingredient release from in situ formed implants and the possibility of using the "burst release" phenomenon to modify the active ingredient release profile at the site of application of this dosage form.

Recovery of pure lithium phosphate from sulfuric acid leaching solutions of spent LiFePO4 batteries by solvent extraction and chemical precipitation

With the increasing use of electric vehicles, the demand for lithium iron phosphate batteries (LiFePO4) has risen sharply. Therefore, the recycling of metals from these batteries at the end of their life is necessary. In this study, a hydrometallurgical process for the recovery of lithium phosphate from spent LiFePO4 batteries was developed. The effects of the parameters on the recovery process, consisting of leaching, solvent extraction, and precipitation were investigated. The addition of H2O2 to the H2SO4 solution was ineffective for the selective leaching of Li(I) over iron. The results showed that Li(I) and iron were completely dissolved by 1.5 mol/L H2SO4, 100 g/L pulp density at 25 ?C for 60 min at 300 rpm. After oxidation of Fe(II) in the leaching solution by addition of H2O2, Fe(III) was completely separated from the solution by five steps of cross-flow extraction with 1.0 mol/L D2EHPA at room temperature. The loaded Fe(III) was successfully separated by four steps of cross-current stripping with 50% (v/v) aqua regia solution. Finally, most Li(I) was recovered by precipitation of lithium phosphate from the iron-free raffinate by maintaining the pH of the solution at 11 and the temperature at 95 ?C for 30 min. The optimum conditions for the complete dissolution of LiFePO4 batteries by sulfuric acid solution and for the separation of iron and lithium ions from the leaching solutions were determined. A hydrometallurgical process was proposed for the recovery of pure lithium phosphate from spent LiFePO4 batteries.

Development of a method to assess the dissolution of soft gelatin capsules containing progesterone in oily suspension

Progesterone is a class II active pharmaceutical ingredient according to the biopharmaceutics classification system, so its absorption is affected by solubility and dissolution rate. The work aimed to develop a dissolution method applicable to soft gelatin capsules of 100 and 200 mg of progesterone. Sink conditions were established based on solubility studies; the dissolution apparatus was selected, and the operational conditions of the method were established using an experimental statistical design. The established conditions were challenged in progesterone products, for which their result was already known from in vivo studies, with the same formulation but different particle size, to evaluate the discriminatory power of the method. The dissolution conditions selected were: United States pharmacopoeia apparatus 3, speed of 30 deeps per minute, dissolution media of 250 ml phosphate buffer solution at pH 6.8 with 4% sodium lauryl sulfate, 30 and 40 mesh at the top and bottom of the cell, respectively, and using a sinker for each capsule evaluated. The method proved to be discriminatory for the formulations studied. In addition to being functional for the evaluation of progesterone release at the product development stage, this method is also useful as a product quality control test.