Theoretical Solubility Research Articles

Solubility study, model correlation and thermodynamics of 3-acetyl-4-hydroxy-2H-chromen-2-one and its chlorinated derivatives in binary solvent mixtures at temperatures from 293.15 to 313.15 K

The solubility of 3-acetyl-4-hydroxy-2H-chromen-2-one (GK-1), 3-acetyl-6-chloro-4-hydroxy-2H-chromen-2-one (GK-2), and 3-acetyl-7-chloro-4-hydroxy-2H-chromen-2-one (GK-3) in binary solvent mixtures of methanol and ethanol was investigated using the gravimetric method over a temperature range of 293.15 K to 313.15 K under atmospheric pressure. Experimental results showed that the mole fraction solubility of GK-1, GK-2, and GK-3 increased with rising temperature and higher co-solvent proportions (0.10 to 0.90 mol fraction). Theoretical mole fraction solubility predictions were made using the Apelblat, Van’t Hoff, Yaws, CNIBS/R-K, and modified Jouyban-Acree models, all of which showed good agreement with the experimental data. Additionally, apparent thermodynamic modeling of GK-1, GK-2, and GK-3 was conducted using the Van’t Hoff equation. The solubility and thermodynamic data obtained are valuable for the processes of production, isolation, separation, and crystallization of these compounds.

Impacts of blending advanced treated water and traditional groundwater supply on lead and copper concentrations and microbial diversity in premise plumbing

In response to stresses on water demands, some regions augment conventional drinking water sources with alternative water supplies such as desalinated seawater and reclaimed wastewater. The advanced treatment of wastewater by reverse osmosis, microfiltration, and advanced oxidation processes can produce high quality water for potable uses. However, if not appropriately stabilized, the resulting water can be corrosive to metal-based distribution pipes and plumbing materials. We conducted long-term premise plumbing pipe loop experiments with copper pipes containing lead solder to test the impact of the introduction of advanced treated water on the water quality. Advanced treated water (ATW) originally at low pH (<7) and low alkalinity (<10 mg/L as CaCO3) was stabilized with a calcite contactor before being blended with baseline ground water (BLW). The effects of percentages of ATW on the release of lead and copper and on the changes in the microbial diversity were monitored. Experiments monitored metal release from pipes receiving (1) only BLW, (2) a series of blends of BLW and ATW that gradually increased from 25 % to 100 % ATW, and (3) an abrupt switch from BLW to 100 % ATW. Introducing 100 % ATW dramatically increased lead release and simultaneously decreased copper release. Pipe scale analysis showed that the introduction of ATW had destabilized sulfate-containing pipe scales, which exposed the copper pipe surface to galvanic corrosion. The dissolution of scale material was associated with a significant decrease in sulfate concentration in the 100 % ATW which was in agreement with theoretical solubility calculations. The impact of blending ATW on microbial diversity was studied via 16S rRNA gene amplicon sequencing. The composition of the microbial communities changed significantly after water was in contact with the copper pipes in experiments with both BLW and ATW. The type of water recirculating in the pipes affected the structure of the microbial community. The results from this study can be useful for water utilities that are considering potable reuse as they develop strategies to mitigate any adverse impacts of water quality changes.

Solubility-controlled early age hydration of carbonate-activated slag: Underlying mechanisms and acceleration via seeding

The low environmental impacts and good performance of carbonate-activated binders have attracted substantial interest, while their intrinsically delayed reaction and prolonged setting times constrain widespread implementation. This study aims to investigate the early-age reaction kinetics of carbonate-activated binders, elucidate the underlying mechanisms and propose controlling methods. Results reveal that hydrotalcite and C-A-S-H gel precursors rapidly reach supersaturation within hours, yet precipitation of these phases remains absent. This phenomenon, coupled with high Si/Ca ratios in the pore solution, exhibits characteristics that may contribute to the observed reaction delays. A prolonged induction period and lethargic strength development are observed owing to the lack of strength-giving phases. The hydrotalcite and C-A-S-H concentrations surpass their theoretical solubility thresholds due to rising ionic strength and salt-in effects. The addition of a pH-neutral layered double hydroxide salt accelerates the reaction, confirming seeding impacts control pore solution saturation limits, constituting the underlying accelerator mechanism.

Solubility determination and thermodynamic modelling of verapamil hydrochloride in methanol-water binary solvent systems from 293.15 K to 323.15 K

Verapamil Hydrochloride is a key calcium channel blocker used to treat cardiovascular disorders and prevent cluster headaches by inhibiting calcium influx, thus improving cardiovascular health. The solubility of Verapamil Hydrochloride (VH) in methanol + water binary solvent systems were studied using a gravimetric method at temperatures from 293.15 K to 323.15 K under atmospheric pressure. The solubility increased with temperature and methanol content, with the highest mole fraction solubility at a 0.90 methanol mole fraction and the lowest at 0.10. Various models, including Apelblat, Van't Hoff, modified Jouyban–Acree, and CNIBS/R-K, were used to calculate theoretical solubility, with RAD and RMSD assessing the model accuracy. Thermodynamic analysis indicated that VH dissolution is endothermic and entropy-driven. This data is valuable for optimizing VH purification and crystallization processes in the pharmaceutical industry.

Hansen solubility parameters and quality-by-design oriented optimized cationic nanoemulsion for transdermal drug delivery of tolterodine tartrate

Tolterodine tartrate (TOT) is a selective anti-muscarinic drug to treat urinary urgency and overactive urinary bladder (OAB) occurring in children, renal disease and elderly patients. Oral delivery is associated with several adverse effects. We addressed HSPiP and QbD (quality by design)-oriented TOT loaded cationic nanoemulsions for transdermal delivery. Hansen solubility parameters (HSP) screened excipients based on theoretical solubility whereas, QbD optimized cationic nanoemulsions (CNE-TOT-6). Formulation characteristic parameters were desirable to execute targeted in vitro drug release and ex vivo permeation profiles. In vitro hemolysis was conducted at varied concentrations whereas, histopathological study supported the safety aspect of CNE-TOT6. A comparative bioavailability was carried out in a rat model. Capmul PG8 (CAP), tween 80, and PEG 400 (polyethylene glycol 400) were screened based on HSP and experimental solubility data. QbD suggested optimized content of CAP, tween 80, and PEG 400 to achieve the lowest value of size (184 nm), maximum % entrapment efficiency (87.2 %), high zeta potential (+32.6 mV), optimum viscosity (47.19 cP), and high extrudability (96 %) as compared to its gel. High gel consistency slowed down the drug release and permeation flux as compared to CNE-TOT6 suspension. Hemocompatible CNE-TOT6 increased pharmacokinetic parameters as compared to the control and gel without causing skin toxicity after application. Thus, HSPiP and QbD oriented cationic nanoemulsions are promising carriers to treat overactive urinary bladder.

Evaluation of a Covalent Library of Diverse Warheads (CovLib) Binding to JNK3, USP7, or p53.

Over the last few years, covalent fragment-based drug discovery has gained significant importance. Thus, striving for more warhead diversity, we conceived a library consisting of 20 covalently reacting compounds. Our covalent fragment library (CovLib) contains four different warhead classes, including five α-cyanoacacrylamides/acrylates (CA), three epoxides (EO), four vinyl sulfones (VS), and eight electron-deficient heteroarenes with a leaving group (SNAr/SN). After predicting the theoretical solubility of the fragments by LogP and LogS during the selection process, we determined their experimental solubility using a turbidimetric solubility assay. The reactivities of the different compounds were measured in a high-throughput 5,5'-dithiobis-(2-nitrobenzoic acid) DTNB assay, followed by a (glutathione) GSH stability assay. We employed the CovLib in a (differential scanning fluorimetry) DSF-based screening against different targets: c-Jun N-terminal kinase 3 (JNK3), ubiquitin-specific protease 7 (USP7), and the tumor suppressor p53. Finally, the covalent binding was confirmed by intact protein mass spectrometry (MS). In general, the purchased fragments turned out to be sufficiently soluble. Additionally, they covered a broad spectrum of reactivity. All investigated α-cyanoacrylamides/acrylates and all structurally confirmed epoxides turned out to be less reactive compounds, possibly due to steric hindrance and reversibility (for α-cyanoacrylamides/acrylates). The SNAr and vinyl sulfone fragments are either highly reactive or stable. DSF measurements with the different targets JNK3, USP7, and p53 identified reactive fragment hits causing a shift in the melting temperatures of the proteins. MS confirmed the covalent binding mode of all these fragments to USP7 and p53, while additionally identifying the SNAr-type electrophile SN002 as a mildly reactive covalent hit for p53. The screening and target evaluation of the CovLib revealed first interesting hits. The highly cysteine-reactive fragments VS004, SN001, SN006, and SN007 covalently modify several target proteins and showed distinct shifts in the melting temperatures up to +5.1°C and -9.1°C.

Ultra‐strong and biodegradable nanocomposite fibers of poly(butylene adipate‐co‐terephthalate)/cellulose nanocrystal prepared by dry‐jet wet spinning

AbstractFiber‐based products constitute a significant portion of plastic waste and cause environmental damage. In particular, discarded sanitary masks and fishing gear disintegrate into microfiber plastics, posing a significant threat to human health and ecosystems. In this study, we developed robust biodegradable nanocomposite fibers of poly(butylene adipate‐co‐terephthalate) (PBAT)/cellulose nanocrystals (CNCs) (1 and 2 wt%) through dry‐jet wet spinning, by using dimethyl sulfoxide (DMSO) as a common solvent. The control PBAT fibers exhibit remarkable mechanical performance with tensile strength and toughness of 160.0 MPa and 43.0 MJ m−3, respectively. CNC addition has a toughening effect with slightly reduced strength but enhanced toughness (148.8 MPa and 69.0 MJ m−3, respectively, for 2 wt% CNC); their mechanical performances are superior to those of previously reported PBAT‐based materials. The remarkable performance of the fibers is attributed to a highly oriented structure with a total draw ratio of 15 after post‐hot drawing. The control and nanocomposite fibers exhibit spot‐like patterns in 2D wide‐angle x‐ray diffraction patterns with Herman's orientation factor of 0.54–0.58. The theoretical Hansen solubility parameter confirmed the poor chemical affinity between the PBAT and CNC. Nonetheless, the rheological characterization revealed that well‐dispersed CNCs with DMSO produced a physical network in the PBAT matrix, resulting in the toughening effect. Such robust nanocomposite fibers consisting of fully biodegradable components are promising alternatives to nondegradable nylon and polyester fibers.Highlights Robust biodegradable nanocomposite fibers of PBAT and CNC are prepared. Nanocomposite fibers are dry‐jet wet spun using DMSO as a common solvent. PBAT fibers exhibit strength and toughness of 160.0 MPa and 43.0 MJ m−3. 2 wt% CNC toughens the PBAT fibers with an enhanced toughness of 69.0 MJ m−3. Rheological results confirm the toughening effect of well‐dispersed CNC in PBAT.

Drug solubility in biorelevant media in the context of an inhalation-based biopharmaceutics classification system (iBCS)

An inhalation-based Biopharmaceutics Classification System for pulmonary drugs (iBCS) holds the perspective to allow for scientifically sound prediction of differences in the in vivo performance of orally inhaled drug products (OIDPs).A set of nine drug substances were selected, that are administered via both the oral and pulmonary routes. Their solubility was determined in media representative for the oral (Fasted State Simulated Intestinal Fluid (FaSSIF)) and pulmonary (Alveofact medium and Simulated Lung Fluid (SLF)) routes of administration to confirm the need for a novel approach for inhaled drugs. The complexity of these media was then stepwise reduced with the purpose of understanding the contribution of their components to the solubilizing capacity of the media. A second reason for varying the complexity was to identify a medium that would allow robust but accurate dissolution testing. Hence, Hank’s balanced salt solution (HBSS) as a medium used in many in vitro biological tests, non-buffered saline solution, and water were included.For some drug substances (salbutamol sulfate, tobramycin, isoniazid, and tiotropium bromide), no significant differences were observed between the solubility in the media used. For other drugs, however, we observed either just small (rifampicin, budesonide, salmeterol) or unexpectedly large differences (beclomethasone dipropionate).Based on the minimum theoretical solubility required for their common pulmonary dose in 10 ml of lung lining fluid, drug solubility was classified as either high or low. Two high solubility and two low solubility compounds were then selected for refined solubility testing in pulmonary relevant media by varying their content of phospholipids, surfactant proteins and other proteins.The solubility of drug substances in simulated lung lining fluids was found to be dependent on the physicochemical properties of the drug substance and the composition of the media. While a pulmonary dissolution medium that would fit all drugs could not be established, our approach may provide guidance for finding the most suitable dissolution medium for a given drug substance and better designing in vitro tests for predicting the in vivo performance of inhalable drug products.

Exploring the Conductivity, Solubility, and thermodynamic properties of sulfonated waste styrofoam through experimental and theoretical studies

In this work, sulfonated WPS (SWPS) was synthesized using concentrated sulfuric acid (Con. H2SO4) at various concentrations (0.01–0.05 mol.dm−3) and temperatures (313 K, 333 K, and 353 K) and the structure was confirmed by various analytical techniques. The degree of sulfonation (DS) values was determined using cation exchange capacity (CEC), 1H NMR, and UV–visible spectroscopy, and to investigate the influence of temperature and various concentration of H2SO4 during the sulfonation reaction. The conductivity of the SWPS was calculated and found to range from 0.23 × 10−6 S.cm−1 to 40.2 × 10−6 S.cm−1. The theoretical solubility parameters of SWPS were determined and compared with experimental values. Using Frenkel-Erying equation, Thermodynamic parameters of SWPS was calculated and also evaluated the correlation between the intrinsic viscosity (η) and viscous flow activation free energy (ΔGv). Our findings contribute to a better understanding of the sulfonation reaction of WPS and the potential applications of SWPS as a functional material.

Effect of the chain length of geraniol esters on the plasticization efficiency with poly(lactide)

This work reports on the development of environmentally friendly PLA formulations utilizing different esters derived from geraniol as plasticizers. Geranyl formate, acetate, propionate, butyrate, isovalerate and caproate at 10 wt% were combined with PLA in formulations that were produced through extrusion and injection moulding processes. Theoretical solubility parameter studies predicted good miscibility between PLA and all the plasticizers. This was confirmed by tensile test, which showed elongation at break values between 200 and 300 %, totally in contrast with the 8 % value of neat PLA. Geranyl acetate and geranyl formate exhibited the highest elongation at break behavior. These values of elongation at break were supported by FESEM images, which showed clear signs of plasticization. The plasticization effect was further corroborated by DSC and DMTA analysis, where a clear decrease in the glass transition temperature was observed from a typical value of 60 °C for neat PLA down to 40–50 °C for the plasticized blends. This was related to an enhanced chain mobility of the amorphous regions of PLA. Moreover, the plasticizers slightly increased the water absorption capabilities of PLA, as demonstrated by an increase in the water contact angle and water uptake for 11 weeks.

Theoretically predicting the solubility of polydisperse polymers using Flory–Huggins theory

Polydispersity affects physical properties of polymeric materials, such as solubility in solvents. Most biobased, synthetic, recycled, mixed, copolymerized, and self-assembled polymers vary in size and chemical structure. Using solvent fractionation, this variety in molecular features can be reduced and a selection of the sizes and molecular features of the polymers can be made. The significant chemical and physical dispersity of these polymers, however, complicates theoretical solubility predictions. A theoretical description of the fractionation process can guide experiments and material design. During solvent fractioning of polymers, a part of the polydisperse distribution of the polymers dissolves. To describe this process, this paper presents a theoretical tool using Flory–Huggins theory combined with molecular mass distributions and distributions in the number of functional groups. This paper quantifies how chemical and physical polydispersity of polymers affects their solubility. Comparison of theoretical predictions with experimental measurements of lignin in a mixture of solvents shows that multiple molecular features can be described well using a single set of parameters, giving a tool to theoretically predict the selective solubility of polymers.

Solubility and solvation energetics of L-histidine in aqueous NaCl/KCl electrolyte media

This article describes the solubility etiquette of an important amino acid L-histidine in chloro aqueous solutions of alkali metals (Na, K) under equilibrium saturated conditions through an analytical gravimetric technique at equidistant temperatures. Different thermodynamic parameters along with transfer Gibbs energies under standard conditions were estimated using theoretical methods and experimental solubilities. The way of surrounding by solvent molecules of solute L-histidine in the used media is discussed based on different modes of interactions occurring during solvation. The experimental section describes that the L-histidine solubility enhances in an aqueous KCl solution rather than in NaCl solution. The drop down in L-histidine solubility with moving up electrolyte concentrations at a certain temperature is caused by the salting-out effect. For the studied amino acid, the salting out effect is more pronounced in NaCl electrolyte at any temperature. Amino acid shows higher solubility with rising temperature in both electrolytes’ solutions. The current study suggests that the physical properties of NaCl and KCl and the size of the L-histidine molecules are two crucial factors for the chemical stability of the protein building unit.

Ethanol–water binary solvent affects phenolic composition and antioxidant ability of Pistacia lentiscus L. fruit extracts: a theoretical versus experimental solubility study

Ethanol–water binary solvent affects phenolic composition and antioxidant ability of Pistacia lentiscus L. fruit extracts: a theoretical versus experimental solubility study

Development of an Amorphous Solid Dispersion Formulation for Mitigating Mechanical Instability of Crystalline Form and Improving Bioavailability for Early Phase Clinical Studies.

In this work, an amorphous solid dispersion (ASD) formulation was systematically developed to simultaneously enhance bioavailability and mitigate the mechanical instability risk of the selected crystalline form of a development drug candidate, GDC-0334. The amorphous solubility advantage calculation was applied to understand the solubility enhancement potential by an amorphous formulation for GDC-0334, which showed 2.7 times theoretical amorphous solubility advantage. This agreed reasonably well with the experimental solubility ratio between amorphous GDC-0334 and its crystalline counterpart (∼2 times) in buffers of a wide pH range. Guided by the amorphous solubility advantage, ASD screening was then carried out, focusing on supersaturation maintenance and dissolution performance. It was found that although the type of polymer carrier did not impact ASD performance, the addition of 5% (w/w) sodium dodecyl sulfate (SDS) significantly improved the GDC-0334 ASD dissolution rate. After ASD composition screening, stability studies were conducted on selected ASD powders and their hypothetical tablet formulations. Excellent stability of the selected ASD prototypes with or without tablet excipients was observed. Subsequently, ASD tablets were prepared, followed by in vitro and in vivo evaluations. Similar to the effect of facilitating the dissolution of ASD powders, the added SDS improved the disintegration and dissolution of ASD tablets. Finally, a dog pharmacokinetic study confirmed 1.8 to 2.5-fold enhancement of exposure by the developed ASD tablet over the GDC-0334 crystalline form, consistent with the amorphous solubility advantage of GDC-0334. A workflow of developing an ASD formulation for actual pharmaceutical application was proposed according to the practice of this work, which could provide potential guidance for ASD formulation development in general for other new chemical entities.

Multiple controls on carbon dioxide sequestration in the beagle channel (Southern Patagonia) in early fall

Subpolar coastal waters are key hotspots in the global carbon cycle. However, the small-scale distribution of partial pressure of carbon dioxide (pCO2) in these environments and the physical and biological controls underlying this variability are still poorly understood. Here, we examine simultaneous high-resolution spatial measurements of wind speed and pCO2, temperature, salinity, and in-vivo chlorophyll-a fluorescence (chl-a fluo, a proxy of phytoplankton biomass) in surface waters that were obtained during an oceanographic survey in the Argentinian Beagle Channel (subantarctic Atlantic Patagonian) in early fall 2017. The 240 km study transect (centered at 55°S - 67°W) was divided into two zones: (A1) The Beagle Channel innermost portion, semi-enclosed and subject to strong continental influence and (A2) its eastern outlet towards the open Southwest Atlantic. Discrete seawater samples were also collected for apparent oxygen utilization (AOU), nutrients and pH measurements. High-resolution spatial measurements revealed the persistence of pCO2 below atmospheric equilibrium, increasing in median (interquartile range 25–75%) from 314 μatm in the inner Beagle Channel (A1) to 348 μatm towards the adjacent open sea (A2). A decrease in atmospheric CO2 sequestration was associated with an increase in water temperature from 9.5 °C to 10.7 °C, salinity from 30.8 to 32.5, and chl-a fluo from 2.24 to 2.91 mg m−3 along the coastal-offshore gradient. Low AOU and nutrient levels were found in regions inside the channel. Indeed, the relationships between CO2 and temperature or salinity were significantly different from those expected from the theoretical solubility effect, indicating a dominance of metabolic over physicochemical controls on this gas. Moreover, physical factors such as vertical stratification contributed to the variable surface pCO2 values. These findings reveal the existence of short-scale spatial variability of CO2 in the Beagle Channel, improving our understanding of the multiple controls on atmospheric carbon sequestration in extensive subpolar continental shelves.

Theoretical and experimental investigation of solubility and Young's modulus models for polyhydroxybutyrate‐based electrospun scaffolds

AbstractOver the past decades, limited strategies have been developed to study nanomechanical properties. The in‐depth study on the nanomechanical properties of electrospun scaffolds can provide better insights at greater scales. Atomic force microscopy (AFM) nanoindentation is an authoritative method that can characterize mechanical properties. In this research, theoretical solubility studies of polyhydroxybutyrate (PHB) in different solvents were initially carried out. Then, three series of PHB‐based mats were prepared, including PHB/lignin, PHB/cellulose nanofiber (CNF), and PHB/lignin/CNF. The theoretical modulus of samples was studied from two different standpoints, through the use of nanoindentation on a single nanofiber. First, scaffolds were considered as a series of short fiber reinforced nanocomposites (NCs). In the second viewpoint, the geometrical structure of each scaffold was considered similar to an open‐cell foam (OCF). Consequently, modeling outputs verified that among NC models, isotropic Halpin‐Tsai presented plausible predictions with ≃93.36 to 99.77% accuracy. In addition, Tetrakaidecahedron indicated more accurate predictions among OCF models for the mats (≃78.99 to 96.15% adaption). Indeed, the theoretical NC and OCF models were able to provide acceptable forecasts for the application range of electrospun fibers. Based on this, nanoscale investigation of mechanical properties can turn a new page to estimate the further application of mats.

Molecular Insight into 6FD Polyimide-Branched Poly(phenylene) Copolymers: Synthesis, Block Compatibility, and Gas Transport Study

A series of 6FDA-DABA (6FD) polyimide and branched poly(phenylene) (PP) block copolymers and homopolymers were successfully synthesized using Diels–Alder and polycondensation reactions. PP and 6FD homopolymer blends in tetrahydrofuran were immiscible. The result coincides with their large chemical dissimilarity and theoretical solubility parameter differences of 25.47 and 33.17 (MJ/m3)1/2. However, 6FD-PP block copolymer solutions were clear, and thin films were robust and creasable. Densities and fractional free volumes (FFV) (0.162–0.346) largely obeyed the rule of mixing, suggesting a “blend-like” morphology. At moderate PP block lengths, two distinct glass transition temperatures (340 and 420 °C) were evident, while large PP block lengths suppressed first-order polyimide transitions entirely. A small-angle X-ray scattering and atomic force microscopy morphological analysis revealed two distinct domains, with separation lengths increasing with the PP block length. Their gas permeation, diffusion, sorption, and separation properties were thoroughly investigated and exhibited a strong correlation with polymer chemistry, block length, and FFV. A block copolymer had an O2 permeability roughly between 6FD and PP, resulting in a 30% increase in O2/N2 selectivity. The N2/CH4 selectivities ranged from 4.2 to 0.58, suggesting that this 6FD-PP system could be efficiently tuned from highly N2-selective to CH4-selective performance. Five structural models, rule-of-mixture, Maxwell, equivalent box model, laminate, and blend, were used to predict gas transport properties. Compared with experimental data, the miscible blend model provided the best results for the 6FD-PP block copolymer system. Block copolymerization by combining highly selective polyimide and highly permeable branched poly(phenylene) provides an opportunity for gas separation tunability and improvement in selected gas pairs.

Relationship between the Hansen solubility parameter and changes in membrane mass-transfer channels: A quantitative model

The relationship between swelling, the difference (Δδ) in theoretical Hansen solubility parameters (HSP) between the two substances, and the change of membrane mass-transfer channel has been controversial. In this work, a completely new parameter, Swell-Cavity Ratio (SCR), defined as the ratio of membrane molecular weight cut off (MWCO), was introduced to characterize the changes in mass transfer channels before and after membrane swelling. Models of the relationship between Δδ and SCR were successfully constructed for nanoporous glassy (SCR = 0.19 × Δδ0.40) and rubbery (SCR = 17.7 × Δδ-0.93) membranes, using the swelling as a bridge. Based on this contradiction in models, we speculate that SCR variation is strongly related to the separation mechanism of the membranes. The theoretical model accurately calculates the influence of the solvent on the membrane mass transfer channel, allowing for the selection of the best membrane material and pretreatment process to maximize treatment efficiency.

Theoretical evaluation of supersaturation of amorphous solid dispersion formulations with different drug/polymer combinations using mathematical modeling

Amorphous solid dispersion (ASD) is a preparation widely used for improving the solubility and low oral absorbability of poorly water-soluble drugs, but the quantitative analysis of its dissolution profiles and its supersaturation status remains an important issue. We previously reported a new mathematical model for analyzing the dissolution characteristics of ASD preparations that enabled evaluation of theoretical solubility of ASDs and crystal precipitation rate constants of ASD preparations. In this study, to analyze the relationship between the mathematical parameters of the model and the dissolution behavior in detail, we simulated the dissolution behaviors upon changing parameters. We quantitatively evaluated the supersaturation of ASD preparations composed of various combinations of two drugs (ibuprofen or indomethacin) and three polymers (polyvinylpyrrolidone (PVP), copovidone or hydroxypropylmethylcellulose (HPMC)). Based on parameter comparison, the difference in the peak of drug concentration between IB/PVP and IB/HPMC ASDs was found to be derived from precipitation rate constant, not the theoretical solubility. In addition, although IMC/PVP ASD had higher solubility than IMC/HPMC ASDs, HPMC could suppress crystal precipitation and maintain supersaturation at higher concentrations than IMC/PVP ASD by comparing parameters derived from model fitting. Thus, our results show that the use of mathematical parameters can illuminate theoretical mechanical information regarding dissolution behaviors of various ASDs and permit a visualization of the character of the dissolution process.

(Digital Presentation) Development of a Bio-Inspired Non-Aqueous Redox Flow Battery Utilizing Anionic Active Materials

Energy storage is an indispensable part of future electrical grids as they increasingly shift toward renewable energy sources.1 Although many other energy storage technologies have shown potential, redox flow batteries are especially promising because of advantages arising from their decoupled power and energy capacity, wide range of possible electroactive materials, wider potential window (in non-aqueous solvents) and safety. 2 However, the nascent non-aqueous redox flow battery (NRFB) technology currently faces key challenges that need to be addressed to ensure their reliability and widespread implementation. Low stability of active material during deep cycling is one such challenge that needs to be addressed while low solubility of active material in organic solvent is another main hurdle that greatly limits energy density.Herein, we present a cost-effective, experimental-theoretical approach 3 , 4 to improve the solubility of a vanadium-based, highly stable, anionic active material known as vanadium-bis-hydroxyiminodiacetate (VBH). This is accomplished by tuning the key thermodynamic quantities of free energy of solvation and free energy of the lattice. We also demonstrate that the lattice free energy, which has been largely ignored in theoretical solubility models, is vital to obtain a meaningful prediction of solubility, and cannot be overlooked. Finally, we report the full cell cycling of the highly soluble VBH, coupled with an anthraquinone, exhibiting excellent cyclability and a reliable spectroscopic method to characterize pre- and post-cycled electrolytes.References(1) IEA. Renewable Energy Market Update 2021 ; Paris, 2021.(2) Dunn, B.; Kamath, H.; Tarascon, J.-M. Electrical Energy Storage for the Grid: A Battery of Choices. Science 2011, 334 (6058), 928-935. DOI: 10.1126/science.1212741.(3) Pahari, S. K.; Gokoglan, T. C.; Visayas, B. R. B.; Woehl, J.; Golen, J. A.; Howland, R.; Mayes, M. L.; Agar, E.; Cappillino, P. J. Designing high energy density flow batteries by tuning active-material thermodynamics. RSC Advances 2021, 11 (10), 5432-5443, 10.1039/D0RA10913D. DOI: 10.1039/D0RA10913D.(4) Visayas, B. R. B.; Pahari, S. K.; Gokoglan, T. C.; Golen, J. A.; Agar, E.; Cappillino, P. J.; Mayes, M. L. Computational and experimental investigation of the effect of cation structure on the solubility of anionic flow battery active-materials. Chemical Science 2021, 12 (48), 15892-15907, 10.1039/D1SC04990A. DOI: 10.1039/D1SC04990A.