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DHDK is a novel diaryl heptanone analog isolated from mistletoe. (1 E, 4 E) 1,7‐bis (4‐hydroxyphenyl) hept‐1,4‐diene‐3‐one (DHDK) exhibits good antitumor activity and excellent stability, but it doesn't have good solubility or bioavailability. In order to improve this deficiency, the structure was modified and five new DHDK derivatives were successfully synthesized. The in vitro cytotoxic activity of DHDK derivatives against four cancer cell lines was determined by Cell Counting Kit‐8 (CCK‐8) assay. The results show that DHDK derivatives exhibit excellent potential, especially for human multiple myeloma cells (KMS‐11) and triple‐negative breast cancer cell line (MDA‐MB 231). The equilibrium solubility and oil‐water partition coefficient of DHDK derivatives were better improved by structural modification. [ABSTRACT FROM AUTHOR]

Imiquimod (IMQ) has been successfully formulated to date mainly as semi-solid lipophilic formulations for topical application. In this study, we investigated the solubility of IMQ in solvents suitable for developing innovative formulations in the form of powder obtained, for instance, by spray drying; thus, water, ethanol, methanol, acetone, acetonitrile, and dimethyl sulfoxide were tested at different temperatures. Temperature variations, stirring intensity, and the contact time between IMQ and the solvent greatly affected the evaluation of IMQ equilibrium solubility. The attainment of the solid–liquid equilibrium requires 13 days starting from solid IMQ and 2 days from a cooled-down supersaturated IMQ solution. A correlation between IMQ solubility and the solubility parameters of solvents was not found. IMQ solutions in water, ethanol, methanol, acetonitrile, and dimethyl sulfoxide were neither ideal nor regular. The Scatchard–Hildebrand equation does not apply to IMQ solutions because of association phenomena due to intermolecular hydrogen bonds and/or π-stacking, as supported by the hyperchromic effect that was very pronounced in highly polar solvents, such as water, with the increase in temperature. Finally, IMQ solubility values measured in acetone cannot be considered reliable due to the reaction with the solvent, leading to the formation of new molecules. [ABSTRACT FROM AUTHOR]

Magnesium (Mg) is not only a typical impurity but also an important valuable metal in the zinc (Zn) hydrometallurgical process. This study proposed the use of freezing crystallization to recover Mg and reduce the Mg2+ concentration in waste electrolyte solutions, meeting the requirements of Zn hydrometallurgy. The experimental results indicated that the Mg2+ concentration decreased from 23.60 g/L to 14.28 g/L under optimal conditions at a temperature of 263.15 K, holding time of 90.00–120.00 min, H2SO4 concentration of 143.00 g/L, crystal seed addition of 50.00 g/L, and agitation speed of 300.00 rpm. The crystallization mother liquor was returned to the Zn hydrometallurgical process. The crystallization product was a mixture of MgSO4·7H2O and ZnSO4·7H2O with an aspect of 17. Notably, this method resulted in no discharge of waste gas, waste liquid, or waste residue. Additionally, during the industrial application process, the average removal efficiency of Mg2+ was 40.15%. The concentration of Mg2+ in waste electrolyte was reduced from 25.00–27.00 g/L to 13.00–15.00 g/L. These results indicated that the method effectively controlled the concentration of Mg2+ in the waste electrolyte and facilitated the recovery of Mg resources from Zn hydrometallurgy. [ABSTRACT FROM AUTHOR]

Solubility is a critical parameter controlling drug absorption after oral administration. For poorly soluble drugs, solubility is influenced by the complex composition of intestinal media and the influence of dosage form excipients, which can cause bioavailability and bioequivalence issues. This study has applied a small scale design of experiment (DoE) equilibrium solubility approach in order to investigate the impact of excipients on fenofibrate solubility in simulated fasted and fed intestinal media. Seven media parameters (bile salt (BS), phospholipid (PL), fatty acid, monoglyceride, cholesterol, pH and BS/PL ratio) were assessed in the DoE and in excipient-free media, and only pH and sodium oleate in the fasted state had a significant impact on fenofibrate solubility. The impact of excipients were studied at two concentrations, and for polyvinylpyrrolidone (PVP, K12 and K29/32) and hydroxypropylmethylcellulose (HPMC, E3 and E50), two grades were studied. Mannitol had no solubility impact in any of the DoE media. PVP significantly increased solubility in a media-, grade- and concentration-dependent manner, with the biggest change in fasted media. HPMC and chitosan significantly reduced solubility in both fasted and fed states in a media-, grade- and concentration-dependent manner. The results indicate that the impact of excipients on fenofibrate solubility is a complex interplay of media composition in combination with their physicochemical properties and concentration. The results indicate that in vitro solubility studies combining the drug of interest, proposed excipients along with suitable simulated intestinal media recipes will provide interesting information with the potential to guide formulation development. [ABSTRACT FROM AUTHOR]

Betulinic acid (BA) and betulin (BE) are naturally pentacyclic triterpenes with documented biological activities, especially antitumor and anti-inflammatory activity. However, their bioavailability in vivo is not satisfactory in terms of medical applications. Thus, to improve the solubility and bioavailability so as to improve the efficacy, 28-O-succinyl betulin (SBE), a succinyl derivative of BE, was synthesized and its solubility, in vitro and in vivo anti-tumor activities, the apoptosis pathway as well as the pharmacokinetic properties were investigated. The results showed that SBE exhibited significantly higher solubility in most of the tested solvents, and showed a maximum solubility of 7.19 ± 0.66 g/L in n-butanol. In vitro and in vivo anti-tumor activity assays indicated both BA and SBE exhibited good anti-tumor activities, and SBE demonstrated better potential compared to BA. An increase in the ratio of Bad/Bcl-xL and activation of caspase 9 was found in SBE treated Hela cells, suggesting that the intrinsic mitochondrial pathway is involved in SBE induced apoptosis. Compared with BA, SBE showed much-improved absorption and bioavailability in pharmacokinetic studies. [ABSTRACT FROM AUTHOR]

This research work’s motive was to investigate the superfluity potential of the BCS-II drug (Dextromethorphan HBr) by solvent shift method to evaluate the impact of polymer gain factor on superfluity potential for the enhancement of bioavailability of orally prolonged release. To maintain the superfluity potential, different drug-release retarding polymers were used (HPMC 15cps, xanthan gum, sodium CMC) in a bio-relevant medium. The outcomes of this, reveal that all polymers remarkably enhanced the solubility of dextromethorphan HBr 1.07-2.49 fold when compared to those without polymer. HPMC and xanthan gum both at 0.1 % w/V showed excellent precipitation inhibitor's role at about 10.2-22.1 factor in SIFsp and 6.04-6.75 factor in PBS (pH 7.4). Elucidation of these results, show that HPMC (15cps) works on the parachute concept and Xanthan Gum on the glider concept. Hence, the superfluity potential is maintained by the selection of excellent polymers in non-formulated drugs to develop the superfluity formulation. [ABSTRACT FROM AUTHOR]

The structure–property relations are examined for apremilast cocrystals and solvates in this work. A unique and large dataset of multicomponent crystal forms is presented including 7 cocrystals and 12 solvates. In total, 15 of the presented multicomponent forms and their crystal structures are published here for the first time. This dataset is unique owing to the extreme crystal packing similarity of all 19 crystal forms. This fact makes the evaluation of structure–property relations significantly easier and more precise since the differences in the crystal lattice arrangement are close to negligible. Properties of the guest molecules used here can be directly correlated with the macroscopic properties of the corresponding multicomponent forms. Interestingly, a considerable correlation was found between the intrinsic dissolution rate of the multicomponent forms and their solubility, as well as the solubility of their guest molecules in the dissolution medium. The latter is of particular interest as it can aid in the design of multicomponent forms with tuned properties.

• Molecular descriptors were used to represent the structure information of amine mocelus in QSPR modeling. • XGBoost and Random Forest models were developed to predict CO 2 solubility in amine solutions using QSPR methods. • The predicted CO 2 solubility closely matched experimental results, showing high accuracy and strong extrapolation potential. • The SHAP method provided interpretive analysis, enhancing the transparency and understanding of model predictions. In this study, a quantitative structure–property relationship (QSPR) model has been designed based on machine learning (ML) to offer a new method to accurately predict carbon dioxide (CO 2) solubility in aqueous amine solutions. Molecular descriptors are used to denote representative features of the amine molecular structure supplemented with amine solution concentration, CO 2 partial pressure, and temperature as inputs to the model. The coefficient of determination (R 2) of the well-trained ML model reaches 0.971, and the average absolute deviation (AAD) of independent experimental validation is 4.785 %, effectively demonstrating the model's reliability and generalization performance. Finally, SHapley Additive exPlanations (SHAP) is adopted to reveal the contribution of different features to the model predictions, making the model more transparent and interpretable. Overall work provides a novel, low-cost, efficient method to predict equilibrium CO 2 solubility in aqueous amine solution and offers a new perspective in developing advanced amine for CO 2 capture. [ABSTRACT FROM AUTHOR]

The simulation of antral conditions for estimating drug apparent equilibrium solubility after a high-calorie, high-fat meal is challenging. In this study, (1) we measured the apparent equilibrium solubility of two model lipophilic drugs, ketoconazole and danazol, in antral aspirates collected at various time points after a minced high-calorie, high-fat meal and a glass of water 30 min after initiation of meal administration, and we designated one point estimate for ketoconazole and one point estimate for danazol; (2) we evaluated the usefulness of FeSSGF-V2 and FEDGAS pH = 3 in reproducing the two point estimates; (3) we evaluated potential compositions of FeSSGF-V3 that simulate the pH, the buffer capacity toward both less acidic and more acidic values, and the antral lipid and protein contents with easily accessible, commercially available products, and (4) we identified the most useful composition of FeSSGF-V3 for reproducing the two point estimates. For both model drugs, apparent solubility in FeSSGF-V2 and in FEDGAS pH 3 deviated substantially from the corresponding point estimate. For FeSSGF-V3, hydrochloric acid, acetates, and FEDGASbuffer pH 3 were evaluated for regulating the pH and buffer capacity, FEDGASgel was used for simulating the lipid content, and Régilait skimmed milk powder was used for simulating the protein content. Level III FeSSGF-V3 prepared with hydrochloric acid, 6.1% (w/v) Régilait, and 2.83% (w/v) FEDGASgel, i.e., one-sixth of FEDGASgel concentration in FEDGAS pH 3, was comparatively the most useful medium for point estimating ketoconazole and danazol apparent solubility in antral contents after water administration in the fed state, induced as requested by regulatory authorities in oral drug bioavailability studies. Level III FeSSGF-V3 prepared by using hydrochloric acid as the principal pH controlling species could be useful in the evaluation of food effects on drug absorption with in silico physiologically based biopharmaceutics modeling approaches and, also, with biorelevant in vitro methodologies.

Aim: The goal of the present work was to formulate zein-decorated rifaximin (RFX) nanosuspension to attain sustained release as well as effectiveness against Escherichia coli (E. coli) . Methods: The RFX nanosuspension was fabricated by using antisolvent addition method followed by coating using hydroalcoholic zein solution. The optimized RFX-NS and RFX-NS@zein was lyophilized for further spectroscopic evaluations. In vitro antibacterial potential was elucidated using well diffusion method whereas MIC value was determined by microbroth dilution method against E. coli for RFX-NS and pure RFX. Results: Box-Behnken Design was employed to assess the effects of independent variables on quality target product profile of RFX-NS. Optimized RFX-NS depicted particle size of 193.5 ± 4.45 nm with 76.49 ± 1.71% drug content. The significant change in particle size and zeta potential confirmed the formation of zein coated RFX-NS (RFX-NS@zein). In vitro release study depicted, 96.91 ± 1.21% release of RFX from RFX-NS in 6 h whereas 97.47 ± 1.99% RFX release was observed from RFX-NS@zein at the end of 12 h. Antibacterial assay of RFX-NS and free RFX against E. coli displayed MIC value of 15.44 ± 0.01 μg/ml and 72.96 ± 0.25 μg/ml, respectively. Conclusion: The results highlighted a significance of nanosuspension for improving the solubility of RFX and its antibacterial potential against E. coli .

Donepezil hydrochloride (DH) is the most used anti-Alzheimer's disease drug, however, its classification according to the Biopharmaceutics Classification System (BCS) is not clear in the literature. BCS is one of the accepted criteria used to grant biowaiver (waiver of in vivo bioequivalence studies) of new drug products. So, the purpose of this work was to elucidate the BCS classification of DH and to raise the discussion about the possibility of biowaiver for new medicines containing it. The polymorphic form was previously identified as form III of DH. The drug showed high solubility in the entire pH range evaluated (1.2 to 6.8, at 37 °C) with a pH-dependent solubility profile. The effective permeability (P eff) values obtained with different DH concentrations, using in situ closed-loop perfusion model were statistically similar (p > 0.05), even when compared to high permeability control used (ketoprofen), demonstrating that DH has high permeability which, associated with its high solubility, allows to classify DH as BCS class 1. Relevant data to evaluate for granting a biowaiver for new medicines were also reviewed from the literature. Based on information reunited new immediate-release drug products containing DH should be eligible for BCS-based biowaiver. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: The application of the Process Oriented Guided Inquiry Learning (POGIL) strategy was carried out to reduce students' misconceptions on solubility equilibrium material. The design of this experimental study was a randomized control group pretest-posttest. The evaluation instrument used is a three-tier multiple-choice test using the Certainty of Response Index. The population of this study was 11-grade students one of the public schools in Pekanbaru city. The study sample was determined randomly after the normality test and homogeneity test was carried out. The experimental class was treated with the application of the POGIL learning strategy while the control class was without the implementation of the POGIL strategy. Data analysis for hypothesis testing is done using the right-party t-test. The results showed that tcount

Formulation and characterization of Luliconazole (LZL) nanosuspensions using modified starch ester polymer to increase solubility. X-ray analysis of A6 and B4 lyophilized nanosuspensions confirmed amorphous nature having % relative crytalinilty of 48.453, 41.374% and crystallite size of 21 and 35 nm; respectively. However, solubility of lyophilized nanosuspension improved by more than 370 fold in comparison to that of pure LZL-API which brings it in soluble form at pH-1.2. In-vitro antifungal studies revealed that lyophilized nanosuspension enhanced activity against fungi yeasts (Candida albican, Candida auris) and Aspergillus (A. Flavus, A. Nigar) when compared to LZL marketed cream. [ABSTRACT FROM AUTHOR]

Diethylethanolamine (DEEA) is a potential candidate for carbon dioxide removal from gaseous streams by reactive absorption. Thermodynamic modeling of the equilibrium behavior of CO2–DEEA–H2O system plays a crucial role in design and simulation. In this study, the improved Kent–Eisenberg model was used to evaluate the equilibrium solubility of CO2 in aqueous solutions of DEEA. The regression coefficients for the model equation were determined through multivariable regression by using experimental equilibrium solubility data from literature. Average absolute relative deviation (AARD) for the fitted parameter was found to be 3.10%. The ability of the model to predict the equilibrium CO2 loadings at different partial pressures for temperatures ranging from 293–353 K and initial amine concentrations of 1–5 M was tested. AARD for the predicted CO2 loading values was found to be 19.16%. [ABSTRACT FROM AUTHOR]

In the present work, artificial neuron network (ANN) based models for predicting equilibrium solubility and mass transfer coefficient of CO2 absorption into aqueous solutions of high performance alternative 4-diethylamino-2-butanol (DEAB) solvent were successfully developed. The ANN models show an outstanding predictive performance over the predictive correlations proposed in the literature. In order to predict the equilibrium solubility, the ANN model were developed based on three input parameters of operating temperature, concentration of DEAB and partial pressure of CO2. An outstanding prediction performance of 2.4% average absolute deviation (AAD) can be obtained (comparing with 7.1–8.3% AAD from the literature). Additionally, a significant improvement on predicting mass transfer coefficient can also be achieved through the developed ANN model with 3.1% AAD (comparing with 14.5% AAD from the existing semi-empirical model). The mass transfer coefficient is considered to be a function of liquid flow rate, liquid inlet temperature, concentration of DEAB, inlet CO2 loading, outlet CO2 loading, concentration of CO2 along the height of the column.

Introduction: Irbesartan (IBS), an angiotensin II receptor (AT1 subtype) antagonist which blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selective binding to AT1 angiotensin II receptor. It belongs to BCS class II drug (low aqueous solubility and high permeability). Improvement of dissolution characteristics of the drug by formulating is being investigated in the current study. Methods: Solid dispersions (SD) formulations were prepared by the melting fusion technique and nanocomposites (NC) were prepared by a single emulsion technique. Eight batches of SD and three batches of NC were formulated in three ratios of drug to polymer (1:1, 1:2, and 1:3). The batches were evaluated for equilibrium solubility studies, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), field emission SEM (FESEM), transmission electron microscopy (TEM), and in vitro dissolution studies. Results: Solubility studies revealed maximum solubility at a 1:2 ratio of solid dispersions and a 1:1 ratio of nanocomposites. No drug-polymer interaction was observed in FTIR results. DSC, SEM, and XRD analysis revealed changes in drug crystallinity i.e. conversion to the amorphous state of drugs. Nanosize of particles in the NC1 batch was confirmed in TEM studies. Solid dispersions and nanocomposites showed significant enhancement of dissolution in comparison to that of the pure drug (100% drug release in approximately 1 hour). Conclusion: Nanocomposites proved superior carriers to solid dispersions in terms of the dissolution enhancement. Further, in vivo studies indicated that the induction of systolic and diastolic blood pressure in the optimized formulation (NC1) was significantly decreased in comparison to the disease control group (P

• NTG is a BCS class II drug, almost insoluble in water, with limited oral bioavailability. • NTG-INA co-crystal prepared through solvent evaporation with ultrasound. • Co-crystals were characterized via DSC, FTIR, XRPD, SEM, and SCXRD. • Equilibrium solubility of the co-crystal was more than twice that of NTG. Nateglinide (NTG) is clinically used to treat type II diabetes. NTG is a Biopharmaceutics Classification System class II drug and is thus almost insoluble in water, limiting its oral bioavailability. The solubility of drugs can be increased through various methods; however, these methods have several limitations. Therefore, this study used solvent evaporation combined with the ultrasonic method to prepare an NTG-isonicotinamide (INA) co-crystal to improve the solubility of NTG and characterized the co-crystal using scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, single-crystal X-ray diffraction (SCXRD), and Fourier transform infrared spectroscopy. The SCXRD results demonstrate that the newly formed crystal material belongs to the P2 1 monoclinic crystal system. A single crystal was formed by NTG and INA in a stoichiometric ratio of 2:2; the crystallographic information is as follows: a = 8.9552 Å, b = 12.6413 Å, c = 21.5877 Å, α=90°, β=98.463 (6)°, γ=90°, Z = 4, R 1 =0.0712, and wR 2 =0.1284. The equilibrium solubility of the co-crystal was more than twice that of NTG, suggesting that it is suitable for further research on its bioavailability and improvement in clinical application. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Orally administered solid drug must dissolve in the gastrointestinal tract before absorption to provide a systemic response. Intestinal solubility is therefore crucial but difficult to measure since human intestinal fluid (HIF) is challenging to obtain, varies between fasted (Fa) and fed (Fe) states and exhibits inter and intra subject variability. A single simulated intestinal fluid (SIF) cannot reflect HIF variability, therefore current approaches are not optimal. In this study we have compared literature Fa/FeHIF drug solubilities to values measured in a novel in vitro simulated nine media system for either the fasted (Fa9SIF) or fed (Fe9SIF) state. The manuscript contains 129 literature sampled human intestinal fluid equilibrium solubility values and 387 simulated intestinal fluid equilibrium solubility values. Statistical comparison does not detect a difference (Fa/Fe9SIF vs Fa/FeHIF), a novel solubility correlation window enclosed 95% of an additional literature Fa/FeHIF data set and solubility behaviour is consistent with previous physicochemical studies. The Fa/Fe9SIF system therefore represents a novel in vitro methodology for bioequivalent intestinal solubility determination. Combined with intestinal permeability this provides an improved, population based, biopharmaceutical assessment that guides formulation development and indicates the presence of food based solubility effects. This transforms predictive ability during drug discovery and development and may represent a methodology applicable to other multicomponent fluids where no single component is responsible for performance. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to harmonize the protocol of equilibrium solubility measurements for poorly water-soluble drugs to lower inter-laboratory variance. The “mandatory” and “recommended” procedures for the shake-flask method were harmonized based on the knowledge and experiences of each company and information from the literature. The solubility of model drugs was measured by the harmonized protocol (HP) and the non-harmonized proprietary protocol of each company (nonHP). Albendazole, griseofulvin, dipyridamole, and glibenclamide were used as model drugs. When using the nonHP, the solubility values showed large inter-laboratory variance. In contrast, inter-laboratory variance was markedly reduced when using the HP.

Yan Yan,1,2 Pengchong Wang,2 Ruiying Li,3 Ying Sun,2 Rui Zhang,2 Chuanchuan Huo,2 Jianfeng Xing,2 Yalin Dong1 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China; 2Department of Pharmaceutics, School of Pharmacy, Xi’an Jiaotong University, Xi’an, Shaanxi, China; 3Department of Clinical Medicine, College of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi, China Purpose: Budesonide (Bud) is a nonhalogenated glucocorticoid with high anti-inflammatory potency and low systemic side effects. However, the poor water solubility of Bud affects its dissolution and release behavior, thus influencing its anti-inflammatory effect. This study was aimed at synthesizing and evaluating novel conjugates of Bud, hoping to increase the anti-inflammatory activity of Bud by improving its water solubility.Materials and methods: Seven novel Bud conjugates (3a–3g) were designed and synthesized in this study. Besides, the equilibrium solubility, cell viability, in vitro and in vivo anti-inflammatory activity, and the hydrolysis behavior of the conjugates in different pH solutions, rat and human plasma, and rat lung homogenate were studied in detail.Results: As compared to Bud, the equilibrium solubility of 3a, 3c, and 3e was significantly increased; 3a, 3b, and 3c significantly inhibited the interleukin-6 production in lipopolysaccharide-induced A549 cells; 3a and 3e could significantly decrease the xylene-induced ear edema; and 3a and 3c were gradually and slowly hydrolyzed into Bud in the alveolar fluid and lung homogenate and broken down quickly in plasma.Conclusion: The amino acid ester compounds budesonide-21-glycine ester (3a) and budesonide-21-alanine ester (3c) were selected as potential conjugates of Bud. This study would provide a theoretical and an experimental basis for the in vivo process of glucocorticoids and the treatment of inflammatory diseases. Keywords: budesonide, glucocorticoid, anti-inflammatory effect, equilibrium solubility, hydrolysis behavior

Solubility is the maximum quantity of a drug dissolved in a given volume of solvent at a specific temperature. Several factors affect equilibrium solubility. Therefore, different solubility data have been reported for a solute in a certain solvent and temperature in the literature. These variations in solubility are one of the possible reasons for unsuccessful attempts of medicinal chemists for developing models as well as deviation of experimental works for solubility prediction in aqueous, non-aqueous and solvent mixtures. The present research aim is to investigate the effect of the amount of excess solid and the type of stirring on the solubility of drugs. The solubility of two antiepileptic drugs, namely sodium phenytoin and lamotrigine was determined in water, ethanol, and HCl 0.1 M at 37 °C. Different excess amounts of drugs were added to the constant volume of solvent. Additionally, different stirring methods such as magnetic stirrer and shake-flask and sedimentation time were investigated on the solubility values. Saturation solubility of drugs after dilution with water was measured using a spectrophotometer, and the concentration was calculated according to the calibration curve. Amount of excess solid, especially when the drug is in ionized form, and sedimentation time after 24 h have a significant effect on solubility values.

The 06Cr18Ni11Ti (321) stainless steel has good corrosion resistance and mechanical properties.However, the addition of Ti leads to the formation of Ti N inclusions, which deteriorates the condition of continuous casting and causes the clogging.The formation of clogging in the submerged entry nozzle (SEN) of 321 stainless steel was studied by scanning electron microscopy (SEM) , energy disperse spectroscope (EDS) and thermodynamic calculation.According to the change of components, three layers in sample were defined:the refractory materials layer, the reaction layer and metal layer from the outer layer to the inner layer of SEN.The results show that the molten steel corrodes the refractory materials of SEN and the high-melting-point slag phase forms.Then Ti N inclusions attach to the inner layer and form curved chain or reticular structure with slag phase, which causes the clogging of SEN.Resultsof thermodynamic calculation indicate that the equilibrium solubility of titanium and nitrogen increases with temperature.There is high Ca/Al proportion in Ca O-Al2O3-Ti O2-5%MgO phase.So controlling the compositions of slag is needed to prevent clogging.

Crystalline solid dispersion of lurasidone hydrochloride (LH) was made with various polar and non‐polar small molecules to overcome the poor aqueous solubility issue. LH‐Glutathione (GSH) solid dispersion in 1:1 ratio was prepared by co‐grinding method and characterized by using differential scanning calorimetry (DSC), powder X‐ray diffraction, Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. GSH acts as antioxidant and reported for anti‐schizophrenic activity may provide synergistic action with LH or reduce the side effects. LH in LH‐GSH solid dispersion (SD) has shown improvement in solubility by 7.9 folds than plain drug which translated in terms of improved dissolution rate by two‐folds. The in vitro dissolution results showed maximum dissolution rate with LH‐GSH SD (97.85 ± 2.40%) compared to plain drug (50.5 ± 3.02%) at 15 min (t15 min, %) and thus, satisfying criteria of immediate release dosage form. DSC and FTIR data confirmed the stability of LH‐GSH SD for 3 months at accelerated stability condition (40 ± 2°C and 75 ± 5% RH). The prepared LH‐GSH SD can be used as a tool to target dual problems that is, enhanced physicochemical properties along with possible management of disorder which could be due to synergism with co‐administered GSH. This approach is thought to be efficiently providing the relief to the psychological patients. [ABSTRACT FROM AUTHOR]

Introduction: Irbesartan (IBS), an angiotensin II receptor (AT1 subtype) antagonist which blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selective binding to AT1 angiotensin II receptor. It belongs to BCS class II drug (low aqueous solubility and high permeability). Improvement of dissolution characteristics of the drug by formulating is being investigated in the current study. Methods: Solid dispersions (SD) formulations were prepared by the melting fusion technique and nanocomposites (NC) were prepared by a single emulsion technique. Eight batches of SD and three batches of NC were formulated in three ratios of drug to polymer (1:1, 1:2, and 1:3). The batches were evaluated for equilibrium solubility studies, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), field emission SEM (FESEM), transmission electron microscopy (TEM), and in vitro dissolution studies. Results: Solubility studies revealed maximum solubility at a 1:2 ratio of solid dispersions and a 1:1 ratio of nanocomposites. No drug-polymer interaction was observed in FTIR results. DSC, SEM, and XRD analysis revealed changes in drug crystallinity i.e. conversion to the amorphous state of drugs. Nanosize of particles in the NC1 batch was confirmed in TEM studies. Solid dispersions and nanocomposites showed significant enhancement of dissolution in comparison to that of the pure drug (100% drug release in approximately 1 hour). Conclusion: Nanocomposites proved superior carriers to solid dispersions in terms of the dissolution enhancement. Further, in vivo studies indicated that the induction of systolic and diastolic blood pressure in the optimized formulation (NC1) was significantly decreased in comparison to the disease control group (P <0.01) at all time intervals along with pure drug (P <0.05). [ABSTRACT FROM AUTHOR]

• The solubility of itopride hydrochloride in eleven pure solvents were determined. • Experimental solubility data were correlated by different models. • Analysis of the solvent effect on the solubility of itopride hydrochloride. • RDF analysis was employed to explain the intermolecular interactions. • Thermodynamic properties of the solution were calculated and discussed. Itopride hydrochloride is a novel prokinetic drug used to relieve gastrointestinal diseases. In this paper, the equilibrium solubility of itopride hydrochloride in selected eleven pure solvents (methanol, ethanol, 1-propanol, 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, acetonitrile, N-methyl-2-pyrrolidone, N, N-dimethylformamide, N, N-dimethylacetamide, dimethyl sulfoxide) was determined by the laser monitoring technique at temperatures ranging from 278.15 K to 323.15 K and pressures of 101.3 kPa. The experimental results showed that the equilibrium solubility of itopride hydrochloride in the selected pure solvents were all positively correlated with temperature and the order of equilibrium solubility at 298.15 K was: dimethyl sulfoxide (28.06)＞methanol (16.63)＞2-methoxyethanol (12.04)＞N-methyl-2-pyrrolidone (8.020)＞N,N-dimethylformamide (5.117)＞N,N-dimethylacetamide(3.576)＞2-ethoxyethanol (1.463)＞ethanol (0.9341)＞2-propoxyethanol (0.4850)＞1-propanol (0.2504)＞acetonitrile (0.1887). In addition, we used the λh model, modified Apelblat model, NRTL model and van't Hoff model to correlate the experimental data of the equilibrium solubility of itopride hydrochloride. Comparing the ARD and RMSD fitted by the four models, it was found that the NRTL model fitted the best, with the 100ARD value less than 5, and the mean values of 100ARD and 104RMSD were 2.15 and 1.61, respectively. Therefore, the NRTL model is more suitable for the correlation of equilibrium solubility data in this experiment. Furthermore, we analyzed the impact of different solvent properties on the equilibrium solubility of itopride hydrochloride, the molecular dynamics simulation was carried out and the interaction between solute and solvent molecules was analyzed by means of radial distribution functions (RDF). Finally, the apparent thermodynamic properties (Δ dis G °, Δ dis H °, Δ dis S °) of the phase equilibrium process of itopride hydrochloride in eleven organic pure solvents were analyzed by using the van't Hoff equation. The results of the analysis showed that it is entropically increasing and heat absorbing during the dissolution process of itopride hydrochloride. [ABSTRACT FROM AUTHOR]

Taxifolin, also known as dihydroquercetin, possesses several interesting biological properties. The purpose of the study was to identify polymorphs of taxifolin prepared using crystallization in different solvents. Data from X-ray powder diffraction, differential scanning calorimetry, and thermogravimetry enabled us to detect six different crystalline phases for taxifolin. Besides the already known fully hydrated phase, one partially hydrated phase, one monohydrated phase, two anhydrous polymorphs, and one probably solvated phase were obtained. The unit cell parameters were defined for three of them, while one anhydrous polymorph was fully structurally characterized by X-ray powder diffraction data. Scanning electron microscopy and hot stage microscopy were also employed to characterize the crystallized taxifolin powders. The hydrate and anhydrous forms showed remarkable stability in drastic storage conditions, and their solubility was deeply evaluated. The anhydrous form converted into the hydrate form during the equilibrium solubility study and taxifolin equilibrium solubility was about 1.2 mg/mL. The hydrate taxifolin intrinsic dissolution rate was 56.4 μg cm−2 min−1. Using Wood’s apparatus, it was not possible to determine the intrinsic dissolution rate of anhydrous taxifolin that is expected to solubilize more rapidly than the hydrate form. In view of its high stability, its use can be hypothesized.

Abstract The phase separation is a crucial step in equilibrium solubility measurements. In the standardized protocol of saturation shake-flask method, sedimentation is proposed as the safest technique. However filtration is widely used in pharma practice. In this paper the effect of the filtration on the measured equilibrium solubility results is presented. The equilibrium solubility values of four model compounds, namely diclofenac sodium, hydrochlorothiazide, papaverine hydrochloride and progesterone were determined at various pH values using the saturation shake-flask method. Two phase separation techniques (sedimentation and filtration) were applied for the separation of the solid from the saturated solution. Four membrane filters, polyvinylidene fluoride (PVDF), polyether sulfone (PES), polytetrafluoroethylene (PTFE) and nylon, as well as an analytical filter paper were investigated. The results obtained by filtration were compared with those measured by sedimentation and the distortion effect of the filter (DEF) on solubility results was expressed in %. The results showed that the filter material type is able to remarkably influence the results in solubility measurements. In several cases, the significant adsorption to the filter caused high inaccuracy in the measured concentration value, more over in some cases failed to work at all. As a main conclusion of this work, if the step of filtration is inevitable, the adsorption to the filter can be mitigated with the appropriate filter type selection what needs some experiences and knowledge about the acid-base chemistry and polar/apolar nature of the sample. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

The recommended method for the biopharmaceutical evaluation of drug solubility is the shake flask; however, there are discrepancies reported about the solubility of certain compounds measured with this method, one of them is candesartan cilexetil. The present work aimed to elucidate the solubility of candesartan cilexetil by associating others assays such as stability determination, polymorphic characterization and in silico calculations of intrinsic solubility, ionized species, and electronic structures using quantum chemistry descriptors (frontier molecular orbitals and Fukui functions). For the complete biopharmaceutical classification, we also reviewed the permeability data available. The polymorphic form used was previously identified as the form I of candesartan cilexetil. The solubility was evaluated in biorelevant media in the pH range of 1.2-6.8 at 37.0°C according to the stability previously assessed. The solubility of candesartan cilexetil is pH dependent and the dose/solubility ratios obtained demonstrated the low solubility of the prodrug. The in silico calculations supported the found results and evidenced the main groups involved in the solvation, benzimidazole, and tetrazol-biphenyl. The human absolute bioavailability reported demonstrates that candesartan cilexetil has low permeability and when associated with the low solubility allows to classify it as class 4 of the Biopharmaceutics Classification System. [ABSTRACT FROM AUTHOR]

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CO2 solubility data are important for the efficient design and operation of the acid gas CO2 capture process using aqueous amine mixture. 2-(Diethylamino)ethanol (DEEA) solvent can be manufactured from renewable sources like agricultural products/residue, and 1,6-hexamethyldiamine (HMDA) solvents have higher absorption capacity as well as reaction rate with CO2 than conventional amine-based solvents. The equilibrium solubility of CO2 into aqueous binary mixture of DEEA and HMDA was investigated in the temperature range of 303.13-333.13 K and inlet CO2 partial pressure in the range of 10.133-20.265 kPa. Total concentration of aqueous amine mixtures in the range of 1.0-3.0 kmol/m3 and mole fraction of HMDA in total amine mixture in the range of 0.05-0.20 were taken in this work. CO2 absorption experiment was performed using semi-batch operated laboratory scale bubble column to measure equilibrium solubility of CO2 in amine mixture, and CO2 absorbed amount in saturated carbonated amine mixture was analyzed by precipitation-titration method using BaCl2. Maximum equilibrium CO2 solubility in aqueous amine mixture was observed at 0.2 of HMDA mole fraction in total amine mixture with 1.0 kmol/m3 total amine concentration. New solubility data of CO2 in DEEA+HMDA aqueous mixtures in the current study was compared with solubility data available in previous studies conducted by various researchers. The study shows that the new absorbent as a mixture of DEEA+HMDA is feasible for CO2 removal from coal-fired power plant stack gas streams. [ABSTRACT FROM AUTHOR]

• Equilibrium solubilities of GuHCl in different binary solvents were investigated. • The molecule interactions of solvent-solvent and solute-solvent were researched through molecular dynamics simulation. • Five thermodynamic models were utilized to regress the observed solubility data. • Dissolution thermodynamic properties were calculated. Solubilities of guanidine hydrochloride (GuHCl) in organic solvents are of great importance for its development and optimization of industrial process. The study of the dissolution characteristics of GuHCl in DMF/2-meoxyethanol/methanol/NMP + n -propanol at different temperatures were experimentally investigated by using laser monitoring method. Results showed that GuHCl solubilities were observed to be increasing with the increment in experimental temperature and rising with higher mass fraction of DMF/2-meoxyethanol/methanol/NMP. Molecular dynamics (MD) simulation technique was utilized to reveal the microscopic behaviors of GuHCl and solvent mixtures and its effect on the dissolving capability of GuHCl in involved solvent systems. Also, five thermodynamic models were selected to regress the observed GuHCl equilibrium solubility. A comparison of the experimental values with corresponding estimated data indicated that the modified Apelblat equation provided the most excellent correlation in modelling GuHCl solubility. Finally, through the analyses of enthalpy change, entropy change and Gibbs free energy change, the dissolution thermodynamic features were evaluated. [ABSTRACT FROM AUTHOR]

ABSTRACT BCS (Biopharmaceutics Classification System) and BDDCS (Biopharmaceutics Drug Disposition Classification System) were proposed as tools for classifying drugs into four categories. Both systems consider the solubility as an important characteristic for the classification of compounds in drug development and in vivo disposition prediction. Although some results of drug solubility can be found in the literature, the aforementioned characteristic is not entirely clear when considering didanosine (ddI). Based on that, the solubility of ddI was evaluated using equilibrium and intrinsic dissolution methods. For the equilibrium method, excess amount of ddI was added to each media until obtaining a supersaturated solution and the mixture was submitted to agitation at 37 °C. For the intrinsic dissolution method, the drug was compressed into the Wood's apparatus matrix and subjected to dissolution in each media with agitation at 37 °C. The results obtained from the equilibrium method indicated that it was necessary 139.37 mL of pH 1.2 media, 87.72 mL of pH 4.5 media, 12.54 mL of pH 6.8 media, 5.03 mL of pH 7.5 media and 7.65 mL of purified water for drug solubilization. Furthermore, a very fast intrinsic dissolution rate (IDR) was obtained for each media: 0.1 mg/min/cm² (pH 1.2), 0.2 mg/min/cm² (pH 4.5), 0.2 mg/min/cm² (pH 6.8), 0.1 mg/min/cm² (pH 7.5) and 0.1 mg/min/cm² (purified water). Based on these results, ddI can be considered as a highly soluble drug for both equilibrium and intrinsic dissolution methods.

Air-jet atomization of solution into droplets followed by controlled drying is increasingly being used for producing nanoparticles for drug delivery applications. Nanoparticle size is an important parameter that influences the stability, bioavailability and efficacy of the drug. In air-jet atomization technique, dry particle diameters are generally predicted by using solute diffusion models involving the key concept of critical supersaturation solubility ratio (Sc) that dictates the point of crust formation within the droplet. As no reliable method exists to determine this quantity, the present study proposes an aerosol based method to determine Sc for a given solute-solvent system and process conditions. The feasibility has been demonstrated by conducting experiments for stearic acid in ethanol and chloroform as well as for anti-tubercular drug isoniazid in ethanol. Sc values were estimated by combining the experimentally observed particle and droplet diameters with simulations from a solute diffusion model. Important findings of the study were: (i) the measured droplet diameters systematically decreased with increasing precursor concentration (ii) estimated Sc values were 9.3 ± 0.7, 13.3 ± 2.4 and 18 ± 0.8 for stearic acid in chloroform, stearic acid and isoniazid in ethanol respectively (iii) experimental results pointed at the correct interfacial tension pre-factor to be used in theoretical estimates of Sc and (iv) results showed a consistent evidence for the existence of induction time delay between the attainment of theoretical Sc and crust formation. The proposed approach has been validated by testing its predictive power for a challenge concentration against experimental data. The study not only advances spray-drying technique by establishing an aerosol based approach to determine Sc, but also throws considerable light on the interfacial processes responsible for solid-phase formation in a rapidly supersaturating system. Until satisfactory theoretical formulae for predicting CSS are developed, the present approach appears to offer the best option for engineering nanoparticle size through solute diffusion models. [ABSTRACT FROM AUTHOR]

In this work, the equilibrium CO2 solubility in the aqueous tertiary amine, N-methyl-4-piperidinol (MPDL) was measured over a range of temperatures, CO2 partial pressures and amine concentrations. The dissociation constant of the MPDL solution was determined as well. A new thermodynamic model was developed to predict the equilibrium CO2 solubility in the MPDL-H2O-CO2 system. This model, equipped with the correction factor (Cf), can give reasonable prediction with an average absolute deviation of 2.0%, and performs better than other models (i.e., KE model, Li-Shen model, and Hu-Chakma). The second-order reaction rate constant (k2) of MPDL and the heat of CO2 absorption (-ΔHabs) into aqueous MPDL solutions were evaluated as well. Based on the comparison with some conventional amines, MPDL revealed a high-equilibrium CO2 loading, reasonably fast absorption rate when compared with other tertiary amines, and a low energy requirement for regeneration. It may, therefore, be considered to be an alternative solvent for CO2 capture. © 2017 American Institute of Chemical Engineers AIChE J, 63: 3395-3403, 2017 [ABSTRACT FROM AUTHOR]

In the present study, trisodium phosphate (TSP) was used as a base solvent for CO 2 capture, and five amines, including 2-((2-aminoethyl)amino)ethanol (AEEA), methyldiethanolamine (MDEA), piperazine (PZ), potassium sarcosinate (K-Sar) and potassium lysinate (K-Lys) were studied as potential additives to improve the absorption performance. In order to investigate and compare the performance of these blended solutions, the corrosion rate, the absorption rate and CO 2 solubility were measured at a total concentration of 2.5 kmol/m 3 and partial pressure of CO 2 ranging from 5 to 50 kPa at 313.15 K, and were compared with monoethanolamine (MEA). The experimental results revealed that PZ as an additive in trisodium phosphate has the highest absorption rate, but the K-Lys + TSP blend solution has the highest loading capacity compared to other additives. In contrast, MDEA showed the lowest effect on the corrosion rate, CO 2 solubility and absorption rate of trisodium phosphate and PZ as the additive has the highest corrosion rate. Furthermore, it was found that these blend solutions have a better performance than pure MEA. In conclusion, K-Lys is a promising additive for trisodium phosphate to apply in the separation of CO 2 from gas streams. [ABSTRACT FROM AUTHOR]

In this present work, the CO2 absorption performance of aqueous 1-diethylamino-2-propanol (1DEA2P) solution was studied with respect to CO2 equilibrium solubility, absorption kinetics, and absorption heat. The equilibrium solubility of CO2 in 2M 1DEA2P solution was measured over the temperature range from 298 to 333 K and CO2 partial pressure range from 8 to101 kPa. The absorption kinetics data were developed and analyzed using the base-catalyzed hydration mechanism and artificial neural network models (radial basis function neural network [RBFNN] and back-propagation neural network [BPNN] models) with an acceptable absolute average deviation of 10% for base-catalyzed hydration mechanism, 2.6% for RBFNN model and 1.77% for BPNN model, respectively. The CO2 absorption heat of 1DEA2P was estimated to be −43.6 kJ/mol. In addition, the ions (1DEA2P, 1DEA2PH+ [ABSTRACT FROM AUTHOR]

Two vortioxetine (VOT) salts with hydrochloride (VOT-HCl and VOT-0.5HCl) were prepared and structurally characterized. VOT-HCl features 1-dimensional P/M helical chains through N–H···Cl hydrogen bond interactions, whereas VOT-0.5HCl possesses a 1-dimensional zigzag structure in which 2 VOT molecules share a single proton through N···H + ···N interactions. VOT-HCl converts into the monohydrate VOT-HCl·H 2 O after dissolution in water, whereas VOT-0.5HCl remains stable. The N 1s X-ray photoelectron spectroscopy analysis shows a characteristic binding energy peak at approximately 398.0 eV for VOT. The shift to high energy occurs at 400.3 eV for VOT-HCl and VOT-HBr, and at 399.7 eV for VOT-0.5HCl, which supports the salt formation by the degree of proton transfer and is confirmed by single-crystal X-ray analyses. The apparent equilibrium solubilities of VOT in water are significantly improved to 2.90 mg/mL (approximately a 32.0-fold increase over that of the free base) for VOT-HCl and to 0.59 mg/mL (approximately a 5.7-fold increase over that of the free base) for VOT-0.5HCl at 25°C. [ABSTRACT FROM AUTHOR]

Gastrointestinal fluid is a complex milieu and it is recognised that gut drug solubility is different to that observed in simple aqueous buffers. Simulated gastrointestinal media have been developed covering fasted and fed states to facilitate in vitro prediction of gut solubility and product dissolution. However, the combination of bile salts, phospholipids, fatty acids and proteins in an aqueous buffered system creates multiple phases and drug solubility is therefore a complex interaction between these components, which may create unique environments for each API. The impact on solubility can be assessed through a statistical design of experiment (DoE) approach, to determine the influence and relationships between factors. In this paper DoE has been applied to fed simulated gastrointestinal media consisting of eight components (pH, bile salt, lecithin, sodium oleate, monoglyceride, buffer, salt and pancreatin) using a two level D-optimal design with forty-four duplicate measurements and four centre points. The equilibrium solubility of a range of poorly soluble acidic (indomethacin, ibuprofen, phenytoin, valsartan, zafirlukast), basic (aprepitant, carvedilol, tadalafil, bromocriptine) and neutral (fenofibrate, felodipine, probucol, itraconazole) drugs was investigated. Results indicate that the DoE provides equilibrium solubility values that are comparable to literature results for other simulated fed gastrointestinal media systems or human intestinal fluid samples. For acidic drugs the influence of pH predominates but other significant factors related to oleate and bile salt or interactions between them are present. For basic drugs pH, oleate and bile salt have equal significance along with interactions between pH and oleate and lecithin and oleate. Neutral drugs show diverse effects of the media components particularly with regard to oleate, bile salt, pH and lecithin but the presence of monoglyceride, pancreatin and buffer have significant but smaller effects on solubility. There are fourteen significant interactions between factors mainly related to the surfactant components and pH, indicating that the solubility of neutral drugs in fed simulated media is complex. The results also indicate that the equilibrium solubility of each drug can exhibit individualistic behaviour associated with the drug's chemical structure, physicochemical properties and interaction with media components. The utility of DoE for fed simulated media has been demonstrated providing equilibrium solubility values comparable with similar in vitro systems whilst also providing greater information on the influence of media factors and their interactions. The determination of a drug's gastrointestinal solubility envelope provides useful limits that can potentially be applied to in silico modelling and in vivo experiments. [ABSTRACT FROM AUTHOR]

• Research the solubility of Glibenclamide in binary mixed solvents of methanol + water, n -propanol + water, isopropanol + water, and acetonitrile + water. • Extended Hildebrand Solubility Approach was applied to explain co-solvence phenomenon. • The solubility data were correlated by some thermodynamic models. • Some apparent thermodynamic properties were evaluated. Equilibrium solubility of glibenclamide (GCM) in aqueous solutions of methanol, n -propanol, isopropanol, and acetonitrile were studied by static technique at temperatures ranging from 288.15 K to 323.15 K under p = 101.3 kPa. When the composition of cosolvent was constant in the four mixed solvents, GCM solubility increased with the rising temperature. When the temperature was fixed, the GCM mole fraction solubility showed positive dependence on the increasing mass fraction of methanol in methanol + water mixture. While in solutions of n -propanol + water, isopropanol + water, and acetonitrile + water, it first increased as the mass fraction of cosolvent (w) added, at around w = 0.9, the solubility reached a maximum value and then it descended. Thermodynamic models like Jouyban−Acree model, modified Apelblat−Jouyban−Acree model, and CNIBS/R-K model were taken to correlate the equilibrium mole fraction solubility of GCM in four solvent mixtures. The maximum RAD and the RMSD values calculated by the CNIBS/R-K model were found in the mixture of methanol + water and didn't exceeded 7.4 × 10−2 and 1.48 × 10−5, respectively. However, the maximum RAD values obtained by the Jouyban−Acree and modified Apelblat−Jouyban−Acree model were found in the mixture of acetonitrile + water and didn't exceeded 5.57 × 10−2 and 5.55 × 10−2, respectively. The RMSD all didn't exceeded 2.54 × 10−5. Hence, the Jouyban−Acree model and modified Apelblat−Jouyban−Acree model are shown to be superior to the CNIBS/R-K model in this work. The experimental data and model parameters obtained will be helpful for the preparation and purification of GCM. [ABSTRACT FROM AUTHOR]