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Background: Application of electromembrane extraction coupled with capillary electrophoresis was studied for ofloxacin extraction from plasma samples. Methods: Ofloxacin migrated from acidic plasma samples through a thin layer of 1-octanol immobilized in the pores of a porous hollow fiber wall into a 10 µL acidic aqueous acceptor solution located inside the lumen of the fiber. Results: Under optimum conditions influencing electromigration (i.e., 20 min of the operation time, stirring speed of 750 rpm, donor phase pH at 4.0, acceptor pH at 3.0, and applied voltage of 30 V across the supported liquid membrane), ofloxacin was extracted from plasma samples with an enrichment factor of 100-fold corresponding to extraction percent of 24%. The calibration curve showed acceptable linearity in the range of 0.2-7.0 µg.mL-1 (R=0.9993). The limits of detection and quantification of 0.05 and 0.2 µg.mL-1 were obtained, respectively. The inter- and intra-day precision and accuracy were obtained below 8.65%. Conclusion: The validated method was successfully processed for the ofloxacin determination in the plasma samples of patients under ofloxacin therapy. There were no interfering peaks which indicates the great selectivity of the developed method.

Abstract Background Morphine serves as a foundation for creating other opioid derivatives, such as hydro/oxymorphine and heroin, which possess enhanced pain-relieving properties but are also prone to addiction and abuse. In cases of morphine overdose, it not only affects multiple immune functions but can also cause severe health complications. Given these concerns and the widespread use of morphine, it is crucial to develop efficient, uncomplicated, and precise methods for accurately detecting morphine in various biological and pharmaceutical samples. Results In this investigation, a novel gold nanoparticle (AuNPs)-based double network hydrogel (DNH) nanoprobe has been fabricated for sensitive quantification of morphine in exhaled breath condensate samples. For that, gelatin/agarose DNH was fabricated through a one-step heating-cooling method in the presence of AuNPs, providing not only chemical stability but also prevent the AuNPs aggregation during synthesis process. In this method, the absorbance intensity of the nanoprobe gradually decreased with increasing morphine concentration due to the interaction morphine with AuNPs surface plasmon. The aggregation of AuNPs by addition of morphine was verified by UV-Vis spectrophotometry. The sensor displayed high sensitivity with detection limit of 0.006 µg.mL-1 in the linear range from 0.01 to 1.0 µg.mL-1. A reliable performance was attained for the spectrophotometric method for determination of morphine in the real samples.

Abstract In this study, a novel fluorescence nanoprobe based on Materials of Institute Lavoisier (MIL-101) metal-organic frameworks embedding into the agarose hydrogel is fabricated using a hydrothermal technique. It uses for sensitive quantification of deferiprone in exhaled breath condensate (EBC) samples. The morphology and characterization of MIL-101/agarose nanocomposite hydrogel is studied by transmission electron microscopy, dynamic light scattering instrument, powder X-ray diffraction analysis, and Fourier transform infrared spectroscopy. The probe shows a reasonable fluorescence intensity quenching in the presence of deferiprone due to the interactions between iron centers in MIL-101 (Fe) and deferiprone, which likely form non-fluorescent complexes. The proposed nanoprobe demonstrates a linear calibration curve from 0.005 to 1.5 µg mL− 1 with a detection limit of 0.003 µg mL− 1. The intra- and inter-day precision of the reported method are 0.3% and 0.4% (n = 5, deferiprone concentration = 1.0 µg mL− 1), respectively. This method demonstrates high sensitivity and specificity towards deferiprone in the EBC samples and also presents a sensing platform with simplicity, convenience, fast implementation, and cost-effective in medical monitoring.

Abstract This study investigates the solubility behavior of Naproxen (NAP) in binary solvent mixtures of 1-propanol (1-PrOH) and 2-propanol (2-PrOH) with ethylene glycol (EG) across a range of temperatures. The solubility of NAP was experimentally determined at five different temperatures (293.15 to 313.15 K), and the data were correlated using various thermodynamic models, including the van’t Hoff, Jouyban-Acree, modified Wilson, mixture response surface, Jouyban-Acree-van’t Hoff. The results demonstrated that NAP’s solubility increases with temperature in both solvent systems. Notably, NAP exhibited higher solubility in mixtures with 1-PrOH compared to 2-PrOH, despite the lower polarity of 2-PrOH. This unexpected trend is attributed to the distinct molecular interactions, including hydrogen bonding, influenced by the structural differences between 1-PrOH and 2-PrOH. The X-ray diffraction analysis confirmed that no polymorphic transformation occurred in NAP during dissolution, maintaining its crystalline structure. The solubility data were well-correlated by the applied models, with overall MRDs% (mean relative deviation percentage) below 6.1.

Abstract Budesonide (BDS) a steroid-based anti-inflammatory drug widely prescribed for various diseases, has a low aqueous solubility. In this study, we investigated cosolvency approach to study the thermodynamic specifications related to the solubility of BDS at the temperature range of 293.2–313.2 K in (1-propanol + water) mixtures applying the shaking flask method. The predictive power of different mathematical models for experimental data in the cosolvency systems was evaluated. For this purpose, the linear and nonlinear mathematical equations such as van’t Hoff model (as a linear model), Buchowski-Ksiazczak equation (as a non-linear), CNIBS/R–K and MRS models (as a linear model for solvent composition at an isothermal condition), modified Wilson model (as a non-linear model for isothermal condition), the Jouyban-Acree model (as a model that considers temperature and solvent composition), and Jouyban-Acree-van’t Hoff model (as a model with no further input data) were studied. Also, the Williams-Amidon excess Gibbs energy model was investigated. In addition, the related apparent thermodynamics of the BDS dissolution process in the desired temperature such as Gibbs free energy, enthalpy, and entropy, were computed by the corresponding equations. Moreover, based on the inverse Kirkwood-Buff integrals, it is demonstrated that BDS is preferentially solvated by water in water-rich mixtures. The accuracy of the fitness was evaluated with mean relative deviations (MRDs%) for back-calculated molar BDS solubility data. The result showed that the maximum solubility of BDS was obtained at 0.7 mass fraction of 1-propanol at all temperatures. Thermodynamic studies demonstrated that BDS dissolution procedures were obtained as endothermic and entropy-driven in almost all cases. The overall MRDs% values for the back-computed BDS solubility in the aqueous mixture of 1-propanol based on van’t Hoff model, Buchowski-Ksiazczak equation, CNIBS/R–K model, modified Wilson model, Jouyban-Acree model, Jouyban-Acree-van’t Hoff model, MRS model, and Williams-Amidon excess Gibbs energy model were found 1.93%, 1.80%, 11.68%, 33.32%, 12.30%, 9.24%, 10.70%, and 6.57%, respectively. Graphical Abstract

Background: Prediction of drugs solubility in mono-solvents at various temperatures revisited concerning the minimization of the experimental efforts. Methods: The reported experimental solubility data of ciprofloxacin (as a model compound) in mono-solvents was mathematically represented using a new correlative mathematical model. The correlative and predictive capabilities of a number of models were investigated and the results were compared with the proposed method. Results: The obtained results revealed that, it is possible to correlate the solubility values for ciprofloxacin in the mono-solvents using a single mathematical model. The correlation accuracy of the model was also compared with those of van’t Hoff, van’t Hoff -Yaws and Apelblat models. To provide predictive tools, the models were trained using a single solubility data points in each mono-solvent and the solubility at other temperatures was predicted. The models provided reasonably accurate predictions. Conclusion: The obtained predictive results are promising and could be recommended to be used in the pharmaceutical industries.

Published equilibrium mole fraction solubilities of phenothiazine in ethanol, propylene glycol and water as mono-solvents at several temperatures were investigated to find standard apparent thermodynamic quantities of dissolution mixing and solvation based on the van’t Hoff and Gibbs equations. Further, by processing the reported mole fraction solubility values of phenothiazine in some aqueous cosolvent mixtures at T/K = 298.2, the inverse Kirkwood–Buff integrals treatment demonstrated preferential hydration of phenothiazine in water-rich mixtures and preferential solvation of this agent by cosolvents in mixtures of 0.24 < x1 < 1.00 in the {ethanol (1) + water (2)} mixed system and mixtures of 0.18 < x1 < 1.00 in the {propylene glycol (1) + water (2)} mixed system.

Abstract This study aimed to measure both the solubility and thermodynamics of salicylic acid in binary solvent mixtures of (2-propanol + ethylene glycol) and (2-propanol + propylene glycol) at different temperatures in the range of 293.2–313.2 K. The experimental solubility data were analyzed using various linear and nonlinear cosolvency models, such as the van’tt Hoff, Jouyban-Acree, Jouyban-Acree-van’tt Hoff, mixture response surface and modified Wilson models and to evaluate the models, the mean relative deviations of the back-calculated solubility data were compared with experimental values. Through this analysis, the apparent thermodynamic parameters, including Gibbs energy, enthalpy, and entropy were calculated using the van’tt Hoff and Gibbs equations for this system. Additionally, the density values for salicylic acid saturated mixtures were also measured and represent mathematically using the Jouyban-Acree model.

In the current work, the performance of the shake-flask and laser monitoring-based techniques for the determination of the solubility is described as a video file. The video is prepared in three parts. The first part is a general explanation of solubility and its manual and automatic measurement methods. The second part is about how to perform the shake-flask method to measure drug solubility, and the third part is about how the laser monitoring -based automatic device works to measure drug solubility.

Vancomycin is employed to treat infections caused by gram-positive bacteria. Ensuring precise vancomycin dosages is essential to avoid the emergence of bacterial resistance. In the current study, a fluorescent nanoprobe was designed for vancomycin determination in exhaled breath condensate samples. The nanoprobe was based on carbon dots (CDs) doped with nitrogen, sulfur, phosphorus, and chlorine (NSPCl-doped CDs). Vancomycin significantly reduced the fluorescence of NSPCl-doped CDs and presented a quenching process in the analytical response of the probe within a concentration range of 0.01–2.0 μg mL−1 due to forming a non-fluorescent complex. The nanoprobe's intra-day and inter-day relative standard deviations were 1.4 % and 3.2 %, respectively. This nanoprobe was successfully used to determine vancomycin in the patients receiving this drug collected from the expiratory circuit of the mechanical ventilator.

Abstract This work focuses on physicochemical features of the choline chloride/propylene glycol deep eutectic solvent (DES) + water mixtures by determining their density values in mono- and mixed- states over various temperatures in the range of 293.15–318.15 K. The density data obtained from measurements were utilized for the computation of various quantities such as excess molar volumes, molar volume, apparent molar volume, limiting apparent molar expansibility, and isobaric thermal expansion coefficient. Furthermore, the experimental densities were fitted to some mathematical equations such as Jouyban-Acree, Jouyban-Acreevan’t Hoff, modified Jouyban-Acree-van’t Hoff, Redlich–Kister and Emmerling. Studies of this nature can provide useful insights into solute–solvent interactions in aqueous solutions of DES, especially about to their novel application in drug solubilization.

Background: There is only limited data for solubility of codeine phosphate in binary systems available, which comes with uncertainties about the prediction accuracy of common thermodynamic models. Methods: This study investigated the codeine phosphate dissolution in N-methyl-2-pyrrolidone(NMP) and ethanol system using shake-flask method and mathematically described generated data by different thermodynamic models. The density as another property was also determined and fitted to the results of the Jouyban-Acree equation. The mean relative deviations were obtained to confirm the model’s accuracy. Moreover, ΔHº, ΔSº, and ΔGº of the dissolution of codeine phosphate in the NMP and ethanol system were calculated using the desired equations at Thm. Results: The dissolution process of codeine phosphate was identified as endotherm, the solubility in the binary mixtures was best at higher mass fractions of NMP and finally, the model predictions were deemed as excellent based on a mean relative deviation that was generally below eight percent. Conclusion: The results of this study could expand the available solubility database for codeine phosphate.

The objective of this research is to propose a general model utilizing the solvatochromic polarity of electronic transition energy (ET) of the Reichardt indicator to predict paracetamol solubility in the solvent mixtures. In order to model validation, the available ET (30) values of nine aqueous mixtures obtained from existing literature sources were utilized. The trained model yielded a relatively accurate estimation of paracetamol solubility in the investigated systems.

Abstract Mesalazine (5-ASA) is a medication utilized to treat inflammatory bowel diseases involving ulcerative colitis and Crohn’s disease. Mesalazine has fewer side effects but the low solubility and bioavailability of it is responsible for its delayed onset of action. Hence, the goal of this study is to determine the molar solubility of 5-ASA in aqueous pseudo-binary mixtures containing low toxic biocompatible choline chloride/ethylene glycol deep eutectic solvent (ChCl/EG DES) with DES mass fraction of 0.0–1.0 using a shake-flask technique at 293.2–313.2 K and approximately 85 kPa. The experimental results indicated that the solubility of 5-ASA enhanced by addition of DES mass fraction and also increasing temperature. The molarity values of 5-ASA were then modelled by some traditional cosolvency models, and regressed each model parameters. The back-computed molarity of 5-ASA using the selected cosolvency models presented a good consistency with the experimental data (lower mean percentage deviation than 5.14%). Moreover, the Gibbs and van’t Hoff equations were employed to compute the thermodynamic functions of 5-ASA dissolution process in ChCl/EG DES + water from the temperature dependency of solubility data. This analysis presented an endothermic and entropy-driven process of 5-ASA dissolution in ChCl/EG DES + water. Furthermore, enthalpy-entropy compensation analysis represented non-linear enthalpy dissolution vs. Gibbs free energy compensation plots with positive and negative slopes for 5-ASA whereas the positive and negative slopes were probably due to the enhance in solvation of 5-ASA by ChCl/EG DES molecules and the solvent-structure loosing, respectively.

The reported total Hildebrand solubility parameter (δ2) value of meloxicam, as calculated based on the group contribution method proposed by Fedors, was compared with those estimated based on the maximum solubility peaks observed in different aqueous cosolvent systems at T = 298.15 K. Thus, the observed δ2 values varied from (19.8 to 29.1) MPa1/2, respectively. Moreover, the Hansen solubility parameters (HSPs) and the total Hildebrand solubility parameter were also determined by using the Bustamante regression method with the reported experimental solubility values of meloxicam in 31 neat solvents (30 organic solvents and water), obtaining the values: δd = 19.9 MPa1/2, δp = 16.9 MPa1/2, δh = 5.7 MPa1/2, and δT = 26.7 MPa1/2. Furthermore, the HSPs of meloxicam were also estimated based on the Hoftyzer–van Krevelen group contribution method, obtaining the values: δd = 17.9 MPa1/2, δp = 20.3 MPa1/2, and δh = 9.2 MPa1/2, and the total solubility parameter as: δT = 28.6 MPa1/2. In addition, the Kamlet–Abboud–Taft linear solvation energy relationship (KAT-LSER) model was also employed to evaluate the role of different intermolecular interactions on the dissolution of meloxicam in different solvents that varied in terms of polarity and hydrogen bonding capability.

Background: According to the poison center data for most countries, more than thousands of people’s exposure to aspirin or salicylate-containing products. So, this work aimed was to offer a rapid colorimetric method for monitoring aspirin concentration in exhaled breath condensate (EBC). Methods: A method based on a redox reaction catalyzed by nanoparticles was validated for the analysis of aspirin. 3,3 ,5,5 –Tetramethyl benzidine /H2 O2 and sodium dodecyl sulfate modified silver nanoparticles were used as the redox reagents and catalyst, respectively. Results: Detection mechanism of aspirin using this system is based on the inhibitory effect of aspirin on the signal intensity of the colorimetric systems. Since the decrement in signal intensity was proportional to aspirin level, a colorimetric method was proposed for its quantification in EBC samples. This method shows a linear relationship with aspirin concentration in the range of 10‒250 mg.L−1 with a relative standard deviation of < 3.5%. Conclusion: This method has great potential for aspirin determination due to some features such as high reliability, and fast response time.

Background: To discover the optimal solvent amounts for using in a particular application, it is vital to achieve some useful information in regard with suitable neat or mixed solvent and drugs equilibrium solubility in them. It is known that the low solubility of drugs such as bosentan (BST) in water negatively effects in vitro and in vivo kinetics of dissolution, affecting in turn its bioavailability along with making several difficulties around designing its liquid formulations. Methods: Solubility of BST in some mixtures of polyethylene glycol 400 (PEG 400) and water was experimentally determined at T = (293.15 to 313.15) K by using a common shake-flask technique followed by UV-visible spectroscopic method. The experimental solubility data in PEG 400 mass fraction (w1) of 0.0 to 1.0 at 298.15 K and in w1=0.0, 0.5 and 1.0 at other temperatures were then correlated by cosolvency models including the Jouyban-Acree, the Jouyban-Acree-van’t Hoff, and the double log-log models and some un-measured solubility data were predicted based on the obtained trained models. Results: The results presented that the aqueous solubility of BST is increased by increasing mass fraction of PEG 400 as well as increasing temperature and reached the maximum value in neat PEG 400 at 313.15 K. Conclusion: The BST solubility in water improved by addition of PEG 400 into it. According to the average relative deviations obtained from the back-computed data with trained models which were < 8.0%, it concluded that the selected models were able to predict the un-measured data with high reliability.

Abstract This work aims to obtain the solubility, density and thermodynamic parameters of deferiprone in propylene glycol and ethanol. For this purpose, a shake-flask technique was applied for solid–liquid equilibration and the spectrophotometry method was employed for solubility measurement. Solubility and density of deferiprone in non-aqueous mixtures of propylene glycol and ethanol were measured in the temperatures 293.2–313.2 K. Some equations including van’t Hoff, the Jouyban-Acree, the Jouyban-Acree-van’t Hoff, the mixture response surface and modified Wilson equations were used for the mathematical data modeling. The apparent thermodynamic parameters of the deferiprone dissolution process were computed and reported.

Molar volumes, excess molar volumes, and partial molar volumes were investigated for glycerol formal + ethanol mixtures by density measurements at several temperatures. Excess molar volumes are fitted by the Redlich-Kister equation and compared with other systems. The system exhibits negative excess volumes, probably due to increased H-bond interactions. Volume thermal expansion coefficients are also calculated. The Jouyban-Acree model was used for density and molar volume correlations at different temperatures. The mean relative deviations between experimental and calculated data were 0.03 ± 0.03% and 0.17 ± 0.13%, respectively, for density and molar volume data. Also, using a minimum number of data points, the Jouyban-Acree model can predict density and molar volume with acceptable accuracies (0.03 ± 0.03% and 0.15 ± 0.12%, respectively).

Background: Lamotrigine is widely used in the management of partial epilepsy, generalized tonic-clonic epilepsy and Lenox-Gastut syndrome and is an add-on therapy in the treatment of complex and simple partial seizures and secondarily generalized tonic-clonic seizures resistant to multiple drug therapy. Methods: In the current study, a fluorometric nanoprobe based on metal–organic frameworks (MOF) was designed for the determination of lamotrigine in exhaled breath condensate (EBC). The MOF nanoprobe consisted of Tb3+ ions as metal part and dimethylformamide (DMF) and 1,10-phenanthroline (Phen) as organic parts of nanoprobe. Results: The used probe shows a weak fluorescence in alkaline media owing to an energy transfer from nitrogen groups of DMF and Phen on carbonyl group of DMF as an antenna for Tb3+ luminescence. However, its fluorescence is enhanced in acidic conditions by protonation of DMF nitrogen atoms and Phen and deactivation of energy transfer pathways of nitrogen groups to carbonyl group. Lamotrigine addition to this fluorescent system leads to quenching in the fluorescence intensity due to reactivation of the above mentioned energy transfer pathways resulting in competitive interaction with H+ ions. Moreover, the inner filter effect (IFE) of lamotrigine on DMF–Tb–Phen MOF NPs is considered as another reason for the observed quenching in the fluorescence of DMF–Tb–Phen MOF NPs. The intensity of the fluorescence was recorded at λem = 545 nm and the difference between fluorescence signal in the absence and presence of lamotrigine was the analytical response. The factors affected on experimental conditions were optimized utilizing a multivariate optimization technique. The validation of nanoprobe response to lamotrigine gives a linear relationship in the range of 0.05 to 2.0 µg⋅mL‒1 with a detection limit of 11.0 ng⋅mL‒1 for lamotrigine. Conclusion: The developed method reveals good repeatability and selectivity for lamotrigine in real samples.

Tacrolimus (Tac) is a well-documented immunosuppressive agent for the prevention of graft-vs-host diseases in several types of organ transplants. The narrow therapeutic window and the individual-variable pharmacokinetics of Tac demonstrate the importance of regular therapeutic drug monitoring (TDM) as an imperative concept for its oral medication regimens. A simple, one-step, selective, and sensitive colorimetric platform is fabricated for the determination of Tac by surface modification of the silver nanoparticles (AgNPs) via norepinephrine (NE) molecules. The attachment of NE and Tac induces the aggregation of the AgNPs, which is observed by color distinction (yellow to brown) and a noteworthy shifting of the absorption peak in the visible region. The fabricated nanoprobe can detect Tac concentrations in plasma samples in two linear ranges from 2 ng/mL to 70 ng/mL and 70 ng/mL to 1000 ng/mL with R2 > 0.99. The limit of detection (LOD) was calculated as low as 0.1 ng/mL. The developed method was applied for the determination of Tac in patient’s plasma samples under Tac medication therapy.

The equilibrium solubility of benzoic acid in water and ethanol, as well as in nine {ethanol (1) + water (2)} mixtures, was determined from T = (293.15 to 323.15) K. Benzoic acid mole fraction solubility in these aqueous-ethanolic mixtures was adequately correlated with some well-known correlation/prediction models, obtaining mean percentage deviations of 2.2 to 7.6%. Apparent thermodynamic quantities, namely, Gibbs energy, enthalpy, and entropy, for the dissolution, mixing and solvation processes, were computed by means of the van ’t Hoff and Gibbs equations. The enthalpy–entropy compensation plot of apparent enthalpy vs. apparent Gibbs energy of dissolution was not linear, indicating enthalpy and entropy mechanisms for transfer. Ultimately, by using the inverse Kirkwood–Buff integrals, it is observed that benzoic acid is preferentially solvated by water molecules in water-rich mixtures but preferentially solvated by ethanol molecules in those {ethanol (1) + water (2)} mixtures of 0.24 < x1 < 1.00.

Background: Sofosbuvir is a potent direct-acting antivirus agent that has been listed as a promising medicine for the treatment of all genotypes of hepatitis C virus. As antiviral drugs could be metabolized to their associated compounds and toxicologically and pharmacologically interfere with the parent drugs, identifying the therapeutic range of drugs would be notable. Methods: In the current study, copper nanoclusters (Cu NCs) are synthesized during the reduction of copper nitrate with hydrazine hydrate in a protected media and used as a nanoprobe for the determination of sofosbuvir in plasma samples. Herein, synchronous fluorescence spectroscopy (SFS) is used for monitoring of fluorescence variation of nanoprobe owing to the excessive benefits compared with the traditional fluorescence. Results: SFS peak of Cu NCs has appeared at 355 nm with ∆λ=80 nm which is decreased in the presence of sofosbuvir. To optimize the reaction factors, a response surface methodology is used and in the optimized conditions, a linear concentration-response plot is obtained in a range of 0.05-6.0 µg mL−1 with a limit of detection of 0.0147 µg mL−1. Conclusion: The developed method also reveals good repeatability and selectivity for sofosbuvir in plasma samples.

This investigation dealt with the thermodynamic properties, saturated solubility values, and solvation behavior of deferiprone as an oral iron chelator agent in non-aqueous mixtures of propylene glycol and 2-propanol using experimental measurements and mathematical correlations. The solubility of deferiprone demonstrated a positive correlation with both temperature and propylene glycol mass fraction. Four mathematical models were employed to correlate the solid-liquid equilibrium data, and the low mean relative deviation values of less than 3.6% illustrate the good agreement of computed data with the experimental data. The apparent thermodynamic behavior of deferiprone dissolution was also investigated according to van’t Hoff and Gibbs equation.

A double solvent-assisted approach was developed for the preparation of AuNPs@UiO-66 based polyvinyl alcohol hydrogel nanocomposite and evaluated its potential as a nanoprobe for the determination of morphine. The characterization and morphology of the synthesized platform were studied and performance comparison for morphine determination was done between the synthesized scaffold and the reported one in our previous work and discussed in detail. Due to the encapsulation of AuNPs inside UiO-66 in a double solvent-assisted approach, no energy transfer was performed with UiO-66 and finally, morphine could not bind with AuNPs. Given these values, such a hydrogel-based matrix prepared with different methodologies with the same thermal stability demonstrates dissimilar potential toward morphine determination in biological samples.

Cancer is still a serious disease with high incidence over the past decades. Many anticancer drugs are discovered and used to treat cancer, among them, taxanes such as paclitaxel and docetaxel have high lipophilicity and low aqueous solubility which is further magnified considering the strong need for administering them by intravenous infusion. Currently, the poor water-solubility of taxanes is improved by prodrug formation, conjugation, inclusion complexation, micellar solubilization and liposome-based formulations. Recent achievements for solubilization of taxanes are reviewed and critically discussed regarding their pharmaceutical and chemical applications.

Background: Meloxicam is a powerful analgesic and anti-inflammatory drug widely prescribed by physicians in current therapeutics. Because of the very low aqueous equilibrium solubility of meloxicam, this property has been studied in {2-propanol + water} mixtures from (293.15 to 313.15) K to expand the solubility database about pharmaceutical compounds in mixed solvents useful for homogeneous liquid dosage forms design. Methods: Flask shaken method and UV-vis spectrophotometry were used for meloxicam solubility determinations. Jouyban-Acree model was challenged for solubility correlation. The van’t Hoff and Gibbs equations were employed here to calculate the respective apparent standard thermodynamic quantities for the dissolution and mixing processes, namely Gibbs energy, enthalpy, and entropy. In addition, the inverse Kirkwood-Buff integrals were employed to compute the preferential solvation parameters of meloxicam by 2-propanol in the mixtures. Results: Meloxicam solubility increases with temperature arising and maximum solubilities are observed in the mixture of x1 = 0.70 at all temperatures. Jouyban-Acree model correlates the meloxicam solubility very well. Dissolution processes were endothermic in all cases and entropy-driven in the interval 0.20 ≤ x1 ≤ 1.00. Non-linear enthalpy–entropy relationship was observed in the plot of enthalpy vs. Gibbs energy exhibiting negative but variant slopes in the composition region 0.00 < x1 < 0.40 and variant negative and positive slopes in the other mixtures. Meloxicam is preferentially solvated by water in water-rich mixtures, it is apparently solvated by water in 2-propanol-rich mixtures, but it is preferentially solvated by 2-propanol in the composition interval of 0.19 < x1 < 0.78. Conclusion: Solid-liquid equilibrium of meloxicam in {2-propanol + water} mixtures has been studied at several temperatures as a contribution to preformulation studies of homogeneous liquid pharmaceutical dosage forms based on this drug.

Early-stage detection is a vital factor in the later treatment and prognosis of cancer. Enhancing the sensitivity and specificity of the cancer detection pathological and experimental approaches can affect the morbidity and mortality of this disease. A folic acid (FA)-functionalized silica quantum dots (SiQDs)/KCC-NH2@SiO2 nanomaterials were synthesized and characterized as a bioimaging agent of the MCF 7 cancer cells. These nanoparticles showed biocompatible nature with specificity towards folate receptor (FR)-overexpressed MCF 7 cancer cells. Viability findings suggested that the SiQDs/KCC-NH2@SiO2/FA nanomaterials have nontoxic nature towards the cells in the concentration of 200 μg/mL. Fluorescence microscopy images were utilized to estimate the cell internalization of the nanoparticles and further verified by the flow cytometry technique. The differentiation ability of the nanoparticles was also approved by incubation with FR-negative HEK 293 normal cells. The SiQDs/KCC-NH2@SiO2/FA nanoparticle exhibited high stability, bright and high quantum yield fluorescence emission, proposing as a high-quality material for in vivo bioimaging of FR-overexpressed circulating tumoral cancer cells (CTCs).

Diethylene glycol monoethyl ether (DEGME) is a hydroalcoholic solvent that gained tremendous attention in the cosmetics, food, nanoformulations, and pharmaceutical industries. Due to its physicochemical features, it has been widely used as a penetration enhancer, surfactant, and solubilizer. Among numerous tradenames defined for DEGME -- Carbitol® (by Dow Chemical Co., USA), and Transcutol® HP, CG, and P. (by Gattefossé Co., France) -- are known to be employed in pharmaceutical industries. Transcutol® CG is utilized only in cosmetics; however, Transcutol® P and Carbitol® are both used in various pharmaceutical topical dosage forms such as creams, gels, etc. Additionally, Transcutol® HP is used in all administration routes. In view of this, the application of DEGME is highlighted in the areas of industry and pharmaceutical sciences. Moreover, in this review the prominent characteristics, pharmacokinetics, and toxicity of DEGME are examined and it is suggested that DEGME is a promising solvent/solubilizer with comparable assignments to other conventional excipients.

The real-time monitoring of food freshness in refrigerators is of significant importance in detecting potential food spoiling and preventing serious health issues. One method that is commonly reported and has received substantial attention is the discrimination of food freshness via the tracking of volatile molecules. Nevertheless, the ambient environment of low temperature (normally below 4 °C) and high humidity (90% R.H.), as well as poor selectivity in sensing gas species remain the challenge. In this research, an integrated smart gas-tracking device is designed and fabricated. By applying pump voltage on the yttria-stabilized zirconia (YSZ) membrane, the oxygen concentration in the testing chamber can be manually tailored. Due to the working principle of the sensor following the mixed potential behavior, distinct differences in sensitivity and selectivity are observed for the sensor that operated at different oxygen concentrations. Typically, the sensor gives satisfactory selectivity to H2S, NH3, and C2H5OH at the oxygen concentrations of 10%, 30%, and 40%, respectively. In addition, an acceptable response/recovery rate (within 24 s) is also confirmed. Finally, a refrigerator prototype that includes the smart gas sensor is built, and satisfactory performance in discriminating food freshness status of fresh or semi-fresh is verified for the proposed refrigerator prototype. In conclusion, these aforementioned promising results suggest that the proposed integrated smart gas sensor could be a potential candidate for alarming food spoilage.

Lung diseases have been recognized as an extensive cause of morbidity and mortality in the worldwide. The high degree of clinical heterogeneity and nonspecific initial symptoms of lung diseases contribute to a delayed diagnosis. So, the molecular and genomic profiling play a pivotal role in promoting the pulmonary diseases. Exhaled breath condensate (EBC) as a novel and potential method for sampling the respiratory epithelial lining fluid is to assess the inflammatory and oxidative stress biomarkers, drugs and genetic alterations in the pathophysiologic processes of lung diseases. The recent studies on the analysis of EBC from both a genetic and epigenetic point of view were searched from database and reviewed. This review provides an overview of the current findings in the tracking of genomic and epigenetic alterations which are potentially effective in better management of cancer detection. In addition, respiratory microbiota DNA using EBC samples in association with pulmonary disease especially lung cancer were investigated. Various studies have concluded that EBC has a great potential for analysis of nuclear and mitochondrial DNA alterations as well as epigenetic modifications and identification of respiratory microbiome. Next-generation sequencing (NGS) based genomic profiling of EBC samples is recommended as a promising approach to establish personalized based prevention, diagnosis, treatment and post-treatment follow-ups for patients with lung diseases especially lung cancer.

Background: Ethanol is considered as a toxic compound when used in excess amounts. The toxic concentration for ethanol was reported to be 1000 – 2000 μg.mL-1 in plasma and serum samples. The aim of the current study was to develop a rapid and catalyst free colorimetric method for determination of ethanol in exhaled breath condensate (EBC) sample. Methods: A redox reaction with dichromate-based colorimetric method was used for determination of ethanol in EBC. Results: The proposed method shows a good sensitivity and selectivity for ethanol in compared with other compounds and biomarkers existing in EBC. The color change can be easily observed by the naked eye in the presence of ethanol in the range of 300 - 8000 μg.mL-1. The quantitative detection of ethanol was fully validated and used for determination of ethanol in EBC of alcohol administrated individuals. Conclusion: This catalyst free colorimetric method has great potential for ethanol determination owing to many desirable properties such as high reliability, high sensitivity, and fast response time.

Veterinary pharmaceuticals have a significant role in animal and human health, therefore, production monitoring and quality control of these pharmaceuticals are of special importance. This work presents an overview on veterinary drug residues in food products and the environment and also discusses the main topics of the guidelines of veterinary pharmaceuticals production, quality control, and usage. This review is composed of more than 100 references and reports the findings of 44 studies conducted on drugs residuals of veterinary food products produced in Iran.

Background: Because of the narrow therapeutic range of tricyclic antidepressant drugs, their determination in biological samples is of great importance. In this work, a fast and environment friendly sample pretreatment method based on a dispersive liquid–liquid microextraction was developed for the extraction and preconcentration of four tricyclic antidepressants including nortriptyline, amitriptyline, desipramine, and clomipramine in urine prior to their determinations by gas chromatography–mass spectrometry. Methods: In the suggested method, an appropriate mixture of Na2SO4 solution (as phase separation agent and disperser) containing isopropanol (extraction solvent) is rapidly injected into an alkaline aqueous sample solution containing Na2SO4 and the analytes. As a result, a cloudy mixture is formed and the tiny droplets of the extractant containing the extracted analytes are collected on the surface of the aqueous phase after centrifuging. Finally, an aliquot of the collected organic phase is removed and injected into the separation system for the quantitative analysis. Results: Under the optimum conditions, the enrichment factors and extraction recoveries were in the ranges of 380–440 and 76–88%, respectively. The limits of detection and quantification were obtained in the ranges of 11–24, and 41–75 ng/L, respectively. The relative standard deviations of the proposed method were ≤ 6.1% for intra– (n=6) and inter–day (n=4) precisions at a concentration of 100 ng/L of each analyte. Conclusion: The introduced method was satisfactorily utilized for the simultaneous determination of the selected tricyclic antidepressant drugs in the patient’s urine samples.

Background: A simple, fast, efficient, and environmentally friendly microextraction technique named salt induced liquid-liquid extraction combined with amine based deep eutectic solvent-dispersive liquid-liquid microextraction method followed by gas chromatography-flame ionization detector was applied for the determination of some anti-seizure drugs in urine samples. Methods: In this method, sodium chloride (30% w/v) was dissolved in the sample solution (adjusted at pH=10) as phase separation agent and iso–propanol was added to the solution. After manually shaking, the solution was centrifuged and the supernatant phase was removed and mixed with choline chloride: benzyl ethylenediamine (85 µL) and the mixture was rapidly dispersed into a deionized water containing 5.0 % w/v, sodium chloride and adjusted at pH=10. The cloudy solution was centrifuged and the sedimented phase was removed and 1 µL of it was injected into the determination system. Results: Under final conditions, the limits of detection and quantification at the ranges of 3.4-6.9, and 11.5-23.3 ng mL-1 were obtained, respectively. The relative standard deviations for intra- and inter day assays were lower than 10.9%. The effect of exogenous and endogenous effect on the performance of the method was studied and the results showed that these factors were nearly effect less on the efficiency. Conclusion: The introduced method was satisfactorily utilized to determinate the selected benzodiazepines drugs in the patients’ urine samples.

Thedensity(ρ) and speed of sound (u)of the binarymixture (diethylene glycol monoethyl ether (carbitol) + propylene glycol (PG)) have been reported at T= (288.15, 298.15, 308.15 and 318.15) K. The excess molar volume ( ) and isentropic compressibility deviation (Δκs) were calculated using the measured data. The obtained values of ( ) and (Δκs) are negative and positive, respectively, and become more negative and more positive with an increase in carbitol mole fraction. The ρ, u, Vm and κs values of the mixture were correlated by the Jouyban-Acree model with high accuracy. Furthermore, the calculated and Δκs values were correlated well by the Redlich-Kister equation.

This article summarizes the publishing activities including bioanalytical and pharmaceutical analyses researches carried out in Iran in 2018 in order to connect academic researchers to those in industry, medical care units and hospitals. A wide spectrum of analytical methods has been used to determine and/or evaluate drug levels in the biological samples, based on physical, chemical and biochemical principles. We have compiled a concise survey of the literature covering 125 reports and tabulated the relevant analytical parameters. Chromatographic and electrochemical methods were found to be the technique of choice for many workers and almost 83% studies were performed by using these methods. This is the first annual review of the literature searching in SCOPUS database for published bioanalytical and pharmaceutical analysis researches in Iran.

Background: Beta-thalassemia major patients require repeated blood transfusion which is associated with iron overload in different organs such as heart, liver, kidney and their related complications. In this study the effects of selenium in iron overload related complications of patients with beta-thalassemia major were assessed. Methods: In this clinical trial, 34 beta-thalassemia major patients over 12 years old were enrolled. Patients with severe renal failure, history of selenium consumption over the last three months, change of blood transfusion pattern, and any change of chelating agent were excluded from the study. For all patients, tablet of selenium 200 µg/day was administered for a month. Blood samples were taken at baseline and after one-month to assess the level of ferritin, total iron-binding capacity (TIBC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (Scr), selenium. Hair loss was assessed by questionnaire before and after intervention. Results: From 34 patients, 27 (79.4%) had deficient level of selenium at baseline. The selenium level was increased after intervention (p=0.005). The level of serum ALT and Scr decreased remarkably after one-month selenium consumption (p=0.007 for both). In addition, the AST level decreased remarkably after intervention (p=0.053). Severe hair loss profile has improved significantly after supplementation (p=0.004). Conclusion: One-month selenium consumption improved liver and kidney function related markers remarkably. Moreover, selenium improved hair profile and severe hair loss in thalassemia patients. Further studies are needed on the effect of selenium administration on liver and kidney function.

Background: Quantitative analyses of antiepileptic drugs are required in clinic and to rational dosage adjustment, the clinician needs the blood levels of these drugs. A high-performance liquid chromatography with spectrophotometric detection has been developed and validated for simultaneous determination of some antiepileptic drugs in plasma of patients with epilepsy. Methods: A simple procedure based on deproteinization by acetonitrile was used for pre-treatment of plasma samples. Liquid chromatographic analysis was carried out on a Nova-Pak® C18 analytical column, using a ternary mixture of potassium dihydrogen phosphate buffer (pH 6.0)-acetonitrile-2-propanol (63:22:15, v/v/v) as the mobile phase, at a flow rate of 1.0 mL min-1. Results: Calibration curves were linear over a range of 1–40 µg mL-1 for phenobarbital, 1–30 µg mL-1 for phenytoin, 0.3–15 µg mL-1 for carbamazepine and 0.5–6 µg mL-1 for carbamazepine epoxide. Conclusion: The simple sample pre-treatment, combined with the fast chromatographic run was used for the determination of antiepileptic drugs for a large number of patient samples.

Background: Recently Sandeepa et al. reported the solubility of benzoic acid in six monosolvents (i.e. tributyl phosphate, diacetone alcohol, methyl-n-propyl ketone, methyl acetate, amyl acetate, and isooctane) and five binary systems (i.e. ethanol + hexane, isopropyl alcohol + hexane and chloroform + hexane, acetone + hexane, and acetone + water) along with some numerical analyses. The reported calculations have been reanalyzed and some recommendations and further computations were proposed. Methods: Further analyses were performed based on combined nearly ideal binary solvent/Redlich-Kister, the modified Wilson model, general single model, Jouyban–Acree model and Jouyban–Acree–van’t Hoff model. Results: The mentioned numerical analyses were used to predict the solubility of benzoic acid in the binary solvent mixtures at various temperatures and the predicted solubility data were compared with their corresponding experimental values by calculating relative deviations. Conclusion: The investigated models provide good estimation of the solubility behavior of benzoic acid in the binary solvent mixtures at various temperatures.

Background: In this research, an enhanced fluorimetric assay was developed for the direct monitoring of verapamil in exhaled breath condensate (EBC). The method is based on a binding–induced rigidity inside the sodium dodecyl sulfate (SDS) micelle which eliminate collisional quenching and vibrational modes responsible for non-radiative decay. This process produces an enhancement in the emission intensity of verapamil. Methods: Fluorescence intensity measurements were made at 15 ˚C on a FP-750 spectrofluorometer with maximum excitation and emission wavelengths of 280 nm and 310 nm, respectively. The important parameters influencing the analytical signal in experimental steps were investigated and optimized. The method was validated with considering of the linearity, recovery and limit of detection. Results: Under the optimized experimental conditions, the calibration graph was linear in the range of 0.02 − 12.0 µg.mL−1 of verapamil with a detection limit of 0.008 µg.mL–1. Conclusion: The proposed method was found to be suitable and accurate for the determination of verapamil and the validated method was successfully used for analysis of verapamil in EBC of patients receiving verapamil with the satisfactory results.

Introduction: Valproic acid (VPA) is an antiepileptic drug used to treat epilepsy and bipolar disorder. Adverse effects of VPA were studied in many reports, however, a dose-response relationship between VPA and its metabolites in epilepsy patients are extremely limited. In this paper, a high efficient method was developed for the preconcentration and determination of VPA and its main metabolite in plasma. Methods: For the extraction and preconcentration of the selected analytes, a volume of an extractant was placed at the bottom of the microtube containing pretreated plasma. The mixture was repeatedly withdrawn from the microtube and pushed-out into it using a 1.0-mL glass syringe and resulted in a cloudy mixture. For further turbidity, the mixture was shaken on a vortex agitator. This procedure was used to analyze the plasma samples of patients with epilepsy (n = 70). Results: The results revealed that in most patients with a low level of VPA relative to its expected level, 3-heptanone concentrations were high. The limits of quantification of 3-heptanone and VPA were 0.04 mg L–1 and 0.2 mg L–1, respectively. A suitable precision at a concentration of 2 mg L-1 for each analyte was obtained (relative standard deviation ≤ 9%). Conclusion: The obtained results indicated that this procedure is easy, sensitive, and reliable, and can be used for the analysis of the selected analytes in the plasma samples of patients with epilepsy.

Abstract Introduction Gut derived toxins such as p-cresol, p-cresyl sulfate (pCS) and indoxyl sulfate (IS), which belong to protein-bound uremic toxins that promote development of fibrosis inflammatory state associated with chronic kidney disease. One possible way to suppress the production of IS and pCS is to increase dietary fiber intake. The aim of the present study was to assess whether increasing dietary fiber, as high amylose diet, can affect the level of conventional and protein bound nitrogenous products. Methods Fifty patients with end stage renal disease (ESRD) on maintenance hemodialysis were randomly assigned to receive a diet containing resistant starch (HAM-RS2) or placebo over 8 weeks spanning February and September 2017 in the 29 Bahman hospital hemodialysis ward in Tabriz, Iran. Of these, 44 patients (23 from HAM-RS2 and 21 control) completed the study. Plasma levels of urea, creatinine, uric acid and other routine parameters were measured at the beginning and after 8 weeks of starting the supplementation. The levels of IS and p-cresol in the collected serum samples were also determined by HPLC at baseline and after intervention. Results There was significant reduction of creatinine and uric acid levels in HAM-RS2 supplemented patients when compared with control group (P

For the first time, a novel aptamer was designed and utilized for the selective detection of rivaroxaban (RIV) using the integration of bioinformatics with biosensing technology. The selected aptamer with the sequence 5′-TAG GGA AGA GAA GGA CAT ATG ATG ACT CAC AAC TGG ACG AAC GTA CTT ATC CCC CCC AAT CAC TAG TGA ATT-3′ displayed a high binding affinity to RIV and had an efficient ability to discriminate RIV from similar molecular structures. A novel label-free electrochemical aptasensor was designed and fabricated through the conjugation of a thiolated aptamer with Au nanoparticles (Au-NPs). Then, the aptasensor was successfully applied for the quantitative determination of RIV in human plasma and exhaled breath condensate (EBC) samples with limits of detection (LODs) of 14.08 and 6.03 nM, respectively. These valuable results provide ample evidence of the green electrogeneration of AuNPs on the surface of electrodes and their interaction with loaded aptamers (based on Au-S binding) towards the sensitive and selective monitoring of RIV in human plasma and EBC samples. This bio-assay is an alternative approach for the clinical analysis of RIV and has improved specificity and affinity. As far as we know, this is the first time that an electrochemical aptasensor has been verified for the recognition of RIV and that allows for the easy, fast, and precise screening of RIV in biological samples.