Miscible Solvents Research Articles

Combination of mixed mode dispersive solid phase extraction with magnetic ionic liquids based dispersive liquid–liquid microextraction for the extraction of anticoagulant drugs from urine samples

In this report, combination of a mixed mode dispersive solid phase extraction with dispersive liquid–liquid microextraction has been performed in order to the effective isolation of three anticoagulant drugs (anagrelide, betrixaban, and apixaban) from urine sample. The extracted drugs were quantified by high performance liquid chromatography–diode array detector. Firstly, analytes were adsorbed onto a mixture of octadecylsilane, graphitized carbon black, and primary secondary amine sorbents which their composition was obtained by a simplex centroid design. To increase the adsorption efficiency, sonication of the solution and sorbents mixture was performed. The loaded analytes onto the sorbent surface were washed employing a water–miscible organic solvent which was utilized as a disperser in microextraction process. The microextraction step was done using a magnetic ionic liquid (as an extractant) and the droplets were sedimented at the bottom of tube with the aid of an external magnetic field. Satisfactory analytical results such as wide linear ranges (0.21–250 µg/L), high enrichment factors (223–247) and extraction recoveries (76–84 %), and low limits of detection (0.04–0.06 µg/L) and quantification (0.16–0.21 µg/L) were obtained using the optimum experimental situations. Lastly, the offered procedure was utilized for the quantification of the opted analytes in urine samples.

Water Miscibility, Surface Tension, Density, and Dynamic Viscosity of Hydrophobic Deep Eutectic Solvents Composed of Capric Acid, Menthol, and Thymol

Deep eutectic solvents (DESs) are rapidly emerging as environmentally benign and viable alternatives not only to common organic solvents but to relatively toxic ionic liquids as well. By judicious selection of the constituents and subsequent variation in their composition, the key physicochemical properties of the DESs can be easily tailored for a specific application. Impact of variation in constituents as well as their composition on important physical properties of natural DESs (NADESs) prepared using a common fatty acid n-decanoic acid (DA) and two naturally occurring monoterpenoids, thymol (Thy) and L(−)-menthol (Men), is assessed. Specifically, water miscibility, surface tension, density, and dynamic viscosity of 17 different DESs of three combinations of constituents, Men:DA, Thy:DA, and Thy:Men in four, four, and nine compositions, respectively, are measured. The water intake by the DESs under ambient conditions varies from 0.6 to 2.7 mol·kg–1 offering a means to gauge their hydrophobicity. Water miscibility is relatively lower for Men:DA DESs and higher for Thy:DA DESs. Surface tension values are within 28.37 mN·m–1 to 31.14 mN·m–1 under ambient conditions; they are higher for the DESs with the Thy constituent and vary systematically with DES composition. The densities of all the DESs are lower than that of water and decrease linearly with increasing temperature. While density does not vary with composition for Men:DA, it is found to increase linearly with an increase in Thy mole fraction for Thy:DA and Thy:Men DESs. The dynamic viscosity of the DESs are relatively lower as compared to the common tetralkylammonium salt- and metal salt-based DESs, and exhibit strong constituent and composition dependence. Rather than the Arrhenius-type expression, the temperature-dependence of the dynamic viscosity better conforms to the Vogel–Fulcher–Tammann (VFT) model with activation energy of the viscous flow varying systematically with the constituent and composition. Reported physical properties and their dependence on constituents/composition of the NADESs will enhance their utility and help establish them as novel alternate media in science and technology.

Combination of dispersive solid phase extraction using MIL–88A as a sorbent and deep eutectic solvent–based dispersive liquid–liquid microextraction for the extraction of some pesticides from fruit juices before their determination by GC–MS

In the present work, a metal organic framework–based dispersive solid phase extraction combined with dispersive liquid–liquid microextraction has been developed for the extraction of some pesticides (diazinon, haloxyfop–R–methyl, hexaconazole, diniconazole, and tebuconazole) from fruit juices before their determination with gas chromatography–mass spectrometry. In the extraction process, first, the synthesized Matériaux de l′Institut Lavoisier–88A (MIL–88A) as a sorbent was added to the aqueous solution and the mixture was vortexed to adsorb the analytes. In the following, the analytes adsorbed onto the sorbent were eluted with a water–miscible deep eutectic solvent. The eluate was taken and used in the microextraction step to further concentrate the analytes. Under the best extraction conditions, satisfactory analytical results such as wide linear ranges (235– 106 ng L–1), high enrichment factors (255–315) and extraction recoveries (51–63 %), and low limits of detection (70–89 ng L–1) and quantification (235–290 ng L–1) were acquired. Lastly, the offered procedure was utilized for the quantification of the opted pesticides in fruit juices.

Mechanisms of separation between tetrahydrofuran and water using hydroxystearic acid

Tetrahydrofuran (THF) is fully miscible in water, and it interacts with it via hydrogen (H) bonds. We discover that the fatty acid hydroxystearic acid (HSA) separates THF from water because it preferentially H-bonds water and increases the proportion of single H-bond donors (SD) relative to double H-bond donors (DD). This change in the coordination of water molecules from DD to SD leads to phase separation between THF and water. We previously established this separation mechanism using sugars and surfactants and other water miscible solvents. Here, we use attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) to prove that this mechanism is also responsible for THF–water separation using HSA, thereby demonstrating the universality of the proposed separation mechanism. Using synchrotron small-angle x-ray scattering, we show how HSA self-assembles into reverse micelles in THF–water mixtures and determine their persistence length and periodicity using a modified Landau model. Reverse micelles host water in their interior and swell upon increasing the water content, as shown by light scattering. They then turn into droplets detectable using optical or confocal microscopy. When THF–water emulsions separate, they yield water-rich and THF-rich free phases. ATR-FTIR reveals that the top phase of THF–water mixtures separated by HSA is THF-rich. Moreover, when Cu2+ ions are in solution, HSA causes their migration into the THF-rich phase, enabling the simultaneous separation of THF and Cu2+ cations from water. This study demonstrates the potential for engineering the water structure to aid in the separation of water-miscible solvents from water with important implications for water treatment.

Cubic mesophases of self-assembled amphiphiles separate miscible solvents

Sodium lauroyl lactylate (SLL) is soluble in water and insoluble in organic solvents, while glycerol monooleated (GMO) is soluble in organic solvents and insoluble in water. These amphiphiles separate miscible solvents (e.g., water and either dimethylsulfoxide, DMSO, dimethylformamide, DMF, acetonitrile, AN, or tehtrahydrofuran, THF). Separation segregates water and the organic solvents into either microdomains (emulsified droplets) or free phases. With mixtures containing 3:7–7:3 DMF:water ratios (v/v), SLL kinetically stabilizes DMF-water emulsions for over a week (longer times were not investigated). Emulsions are DMF in water with DMF:water ratios ≤ 2:3, and water in DMF for DMF:water ratios ≥ 1:1. Optical microscopy and SEM illustrate emulsification, and confocal microscopy qualitatively shows segregation between DMF (dyed with fluorescein) and water (which appears dark in confocal images). Water droplets in DMF are kinetically stable because they are surrounded by self-assembled SLL cubic mesophases, either gyroid or primitive, depending on the SLL and DMF concentrations (as demonstrated by x-ray diffraction, XRD). SLL also stabilizes DMSO-water emulsions (for over a week), thereby segregating the two solvents with similar mechanisms. DMSO-water separation is quantitatively demonstrated by mid-infrared (mid-IR) spectromicroscopy. Separation between AN and water occurs for AN-water mixtures in which SLL has intermediate solubility, i.e., with 3:2 and 4:1 AN:water ratios (v/v). In this range, SLL yields emulsions which destabilize overnight, separating into AN-rich and water-rich phases, as demonstrated using nuclear magnetic resonance (NMR). In water, SLL self-assembles into primitive cubic liquid mesophases and it affects hydrogen bonding (H-bonding) of water, as shown by deconvolving the H-bond peak into peaks representative of different water clusters, comprised of water molecules donating and accepting a different number of H-bonds. In water, SLL induces a blue shift of the hydrogen bonding (H-bonding) of absorbance peaks for double (DD) and single (SD) H-bond donors, indicating that it strengthens H-bonding. Importantly, it increases the ratio between the amplitude A of SD relative to DD, and SD are most effective at structuring water. As a result, SLL would inhibit interactions between organic solvents and water, initiating separation. Similar to SLL, GMO is known for its ability to form cubic mesophases. GMO stabilizes emulsions of water miscible solvents (THF, DMSO and DMF) and water. This result indicates that selected amphiphiles self-assembled into cubic mesophases can emulsify miscible solvents.

Spontaneous water-on-water spreading of polyelectrolyte membranes inspired by skin formation

Stable interfaces between immiscible solvents are crucial for chemical synthesis and assembly, but interfaces between miscible solvents have been less explored. Here the authors report the spontaneous water-on-water spreading and self-assembly of polyelectrolyte membranes. An aqueous mixture solution containing poly(ethyleneimine) and poly(sodium 4-styrenesulfonate) spreads efficiently on acidic water, leading to the formation of hierarchically porous membranes. The reduced surface tension of the polyelectrolyte mixture solution drives the surface spreading, while the interfacial polyelectrolytes complexation triggered by the low pH of water mitigates water-in-water mixing. The synergy of surface tension and pH-dependent complexation represents a generic mechanism governing interfaces between miscible solvents for materials engineering, without the need for surfactants or sophisticated equipment. As a proof-of-concept, porous polyelectrolyte hybrid membranes are prepared by surface spreading, exhibiting exceptional solar thermal evaporation performance (2.8 kg/m2h) under 1-sun irradiation.

Towards potentiometric detection in nonaqueous media: Evaluation of the impacts of organic solvents on polymeric membrane ion-selective electrodes

Polymeric membrane ion-selective electrodes (ISEs) have been widely used in various fields including clinical diagnosis, environmental monitoring and industrial analysis. Although most samples of analytical interest measured by the ISEs are aqueous solutions, the applications of these electrodes in nonaqueous media are often inevitable. Unfortunately, so far, little has been known about the extent to which the properties of the ISEs could be affected by the organic solvents. Herein, the feasibility for the applications of the polymeric membrane ISEs in nonaqueous media has been investigated. A polymeric membrane Ca2+-ISE is chosen as a model of potentiometric sensors. Four typical water miscible organic solvents (three protic solvents: ethanol, acetic acid, and methanol, and one aprotic dipolar solvent: acetonitrile) are used as the representative examples. Experiments show that the aprotic solvent acetonitrile has the strongest destructive ability towards the sensing performance of the ISE in terms of Nernstian slope and selectivity coefficient. Moreover, the effect on the sensing performance depends on the kind of the protic solvent, the immersion time and the polarity of the membrane plasticizer. We believe that the obtained results could promote further applications of the polymeric membrane ISEs in the organic solvent-containing samples, which could significantly extend the application scope of the ISEs.

Preconcentration of liposoluble constituents in Salvia Miltiorrhiza using acid-assisted liquid phase microextraction based on a switchable deep eutectic solvent

A switchable deep eutectic solvent-based liquid-phase microextraction was proposed and applied to the preconcentration and determination of liposoluble quality-markers of diterpenoid quinones (dihydrotanshinone I, cryptotanshinone, tanshinone I, and tanshinone IIA) in traditional Chinese medicine coupled with high performance liquid chromatography-ultraviolet detection. In the procedure, the hydrophilic deep eutectic solvent of diethanolamine-hexanoic acid (molar ratio 1:1) was prepared and added into the sample phase as an extractant, and a homogeneous solution was formed under slight vortex stirring. After the addition of HCl solution, the deep eutectic solvent miscible with the sample phase was converted to hydrophobic form, and a cloudy solution was generated. Then, the upper hydrophobic layer enriching the target analytes was collected through centrifugation for high performance liquid chromatography analysis. Several critical parameters affecting the extraction performance including the composition and consumption of switchable deep eutectic solvent, the type and amount of acid, salt amount and extraction time were investigated and optimized. Moreover, the structures of the deep eutectic solvent and the recovered hydrophobic layer were both characterized using Fourier transform infrared spectroscopy, further demonstrating the switching mechanism of the extractant during the extraction process. Under the optimal conditions, enrichment factors of diterpenoid quinones ranged from 59 to 274. Good linearities (r≥0.9963), low detection limits (0.5–0.7 ng/mL), satisfactory precisions (relative standard deviations 0.5%-8.6%) and accuracies (recoveries 94.6%-104.6%) were also obtained. Comparing the proposed switchable deep eutectic solvent-based liquid-phase microextraction with other published methods, the characteristics of the procedure were summarized. The developed method was successfully applied for the preconcentration of four liposoluble diterpenoid quinones from a traditional Chinese herbal medicine of Salvia Miltiorrhiza.

Coupling of Fused Deposition Modeling and Inkjet Printing to Produce Drug Loaded 3D Printed Tablets.

In the current study, we have coupled Fused Deposition Modelling (FDM) for the fabrication of plain polyvinyl alcohol (PVA) tablets followed by dispensing of minoxidil ethanolic solutions using inkjet printing. The use of a drop-on-solid printing approach facilitates an accurate and reproducible process while it controls the deposition of the drug amounts. For the purpose of the study, the effect of the solvent was investigated and minoxidil ink solutions of ethanol 70% v/v (P70) or absolute ethanol (P100) were applied on the plain PVA tablets. Physicochemical characterization showed that solvent miscibility with the polymer substrate plays a key role and can lead to the formation of drug crystals on the surface or drug absorption in the polymer matrix. The produced minoxidil tablets showed sustained release profiles or initial bursts strongly affected by the solvent grade used for dispensing the required dose on drug loaded 3D printed tablets. This paradigm demonstrates that the coupling of FDM and inkjet printing technologies could be used for rapid development of personalized dosage forms.

Visualization of liquid interface and reaction front flow in partially soluble solvent

In this study, visualization of the reaction in partially miscible solvents has been conducted using the Schlieren method, an indicator addition method and PIV method. The CH3COOH in C4H10O was set on the NaOH in water against the vertical downward direction of the Hele-Shaw cell. It was found that various convection phenomena could be induced by the generation of H2O and CH3COONa during chemical reaction, which were depended on the ratio of initial concentration, R = CCH3COOH,0/CNaOH,0. For R = 1, the horizontal travelling wave was observed from the left-hand side to the right-hand side in the HS, which could be caused by Marangoni convection due to the locally H2O concentration. After that vertical convections were also observed on the interface of the C4H10O and water and below the interface. They could be caused by Rayleigh Tayler instability and the salt finger, respectively. It was found that the time change of the reaction front from the interface was largely divided by R. For R <1, the change in the reaction front position gradually approaches a constant value in a few seconds. On the other hand, for R≧1, the reaction front increased proportionally t0.5.

Extraction of glucocorticoids from water into acetonitrile using polyol induced extraction with ultra performance liquid chromatography and triple quadrupole mass spectrometry (PIE-UPLC-MS-MS)

Polyol-induced Extraction (PIE) was used for the extraction and UPLC-MS-MS was used for the analysis of glucocorticoids in water. The focus of this work was to demonstrate PIE as an effective technique that allows extraction of solutes between miscible solutes using a phase separating agent, with an example analysis of glucocorticoids. In this work glycerol is used as the mass separating agent in the extraction of glucocorticoids from water into acetonitrile. Eight glucocorticoids were extracted by PIE and analyzed by UPLC-MS-MS. Extraction conditions were optimized, and extraction results were compared to non-extracted glucocorticoid standards and to literature methods. Extraction was optimized at 0 °C, in 10 mL of a 1:1 ACN/Water mixture 2 mL of glycerol added as phase separating agent. Calibration curves showed overall correlation of r 2 > 0.99. Precent relative standard deviation below 4%was obtained for all analytes. Limits of detection were obtained between 3–4 ng/mL by the IUPAC method and 40–200 ng/mL by a propagation of errors method. PIE is demonstrated to be a simple and quick method for extracting glucocorticoids from water into a miscible polar solvent, acetonitrile.

Facile purification protocol of CsPbBr3 nanocrystals for light-emitting diodes with improved performance

Light-emitting diodes (LEDs) based on CsPbBr3 nanocrystals (NCs) show excellent performance in terms of external quantum efficiency (EQE) and brightness. Removal of impurities after NC synthesis is a necessary and critical step to achieve such high performance. In fact, the optical and electronics properties of CsPbBr3 NCs are greatly affected by how the NCs are purified from the synthetic by-products, unreacted reagents, and organic ligand excess. Perovskite NC purification protocols must consider the ionic nature of the inorganic core, the labile nature of the ligand to surface bond, and the dynamic equilibrium between the surface-interacting and free form organic ligands to prevent NC damaging with subsequent loss of photoluminescence. Nowadays, the most employed purification protocol involves NC precipitation based on a diminished non-polar environment achieved by adding a low-dielectric constant miscible solvent to the NC solution (i.e., ethyl acetate to toluene), followed by redispersion of the precipitate in a storage solvent. Here, we explored the possibility to precipitate impurities left in the NC solution exploiting variations in solubility at decreasing temperature: by taking NC solutions at −20 °C overnight and by collecting the respective supernatant we obtain CsPbBr3 NC solutions which leads to LEDs with improved EQE. The freezing process at −20 °C gives rise to NC solutions that retain the pristine optical and electronic properties while the LED performances display a 3 times increase in terms of EQE (EQEmax = 8.9%) with respect to NCs treated with anti-solvent only. Finally, we show that our purification protocol can be applied to CsPbBr3 NCs obtained via different synthetic methods, thus demonstrating the versatility of our facile purification protocol.

Simultaneous Realization of Superoleophobicity and Strong Substrate Adhesion in Water via a Unique Segment Orientation Mechanism.

The underwater superoleophobicity of a coating is often caused by its preferential water affinity, which, however, normally weakens the substrate adhesion property. In this work, a new strategy is reported for achieving strong underwater adhesion between a well-designed amphiphilic polyurethane coating and a diverse range of substrates while also rendering the coating surface's superoleophobicity. When the coating, which is a mixture of an amphiphilic polyurethane and a water miscible solvent, is immersed in water, the hydrophobic segments aggregate to orientate and pile along the surface of substrates via a segment orientation mechanism triggered by solvent exchange with water penetration to exert strong adhesion. At the same time, the hydrophilic segments will physically crosslink to form a hydrogel coating, endowing the substrate with underwater superoleophobicity. This work provides a facile, versatile, and scalable approach for the future design of superoleophobic coatings in a water environment.

Highly dispersed Cu catalyst based on the layer confinement effect of Cu/Zn/Ga-LDH for methanol synthesis

The small amount of promoter has shown increase in the methanol formation rate by several folds. Hence, hydrotalcite having sufficient trivalent cations are preferred; however, traditional coprecipitation route often leads to poor Cu dispersion owing to higher cationic charge in the layered structure that result in aggregation of the sheets. The present paper reports synthesis of porous, nanostructured Cu/ZnO/Ga2O3 catalysts from pure phase hydrotalcite precursors by using aqueous miscible organic solvent treatment method. The 20% Ga containing catalyst showed ca. 2.5-fold increase in both surface area and % dispersion of the exposed Cu as compared to that prepared from standard coprecipitation method with similar composition. The stabilization induced by mutual dispersion of Cu, Zn and Ga components in the exfoliated sheets resulted in confinement of the Cu particle size up to 5 nm in the spent catalyst. The best performing catalyst of the series, Cu0.4Zn0.4Ga0.2-LDO exhibited STY of 762 mg•gCat−1•h−1 for methanol formation from syngas which was decreased by only 8.6% during 50 h of the reaction on stream. Further, it was revealed that, Ga is more conductive to stabilization of Cu as compared to Al, resulting in 23% higher methanol formation rate as compared to the Al containing catalyst.

Solvent Effect on Photo / Thermo Responsive behaviour and Application of Poly(N-isopropylacrylamide) End-capped with 4-Propoxyazobenzene in Aqueous Media

ABSTRACT The photoisomerisation behaviour of Poly(N-isopropylacrylamide) end-capped with 4-propoxyazobenzene (PNIPAM-Azo-OC3H7) was studied in a conconsolvent mixture of water and dioxane. The trans-cis isomerisation rate of PNIPAM-Azo-OC3H7 was mildly affected by the solvent compositions. Interestingly, the addition of dioxane could not only change the lower critical solution temperature (LCST) of PNIPAM-Azo-OC3H7 aqueous solution but also accurately controlled the increase or decrease in the LCST during UV irradiation. The LCST change (ΔT) could be adjusted from −5.0°C to 10.0°C, which was affected by the cononsolvent type, the second solvent and polymer concentration. Transmission electron micrographs (TEMs) showed that the PNIPAM-Azo-OC3H7 solution could self-assemble into different nano-micelles in different amounts of miscible solvents. UV irradiation of PNIPAM-Azo-OC3H7 solution was found to induce different changes in particle shape and size, which in turn led to either decrease or increase in the LCST changes in this novel responsive system. Furthermore, Nile red was tested here as a fluorescence probe for photo-induced release from PNIPAM-Azo-OC3H7 micelles, and the results suggested that this polymer could be used as a hydrophobic chemotherapeutic drug carrier for controlled release.

Promising integrated technique for the treatment of highly saline nanofiltration rejected stream of steel industry

This work presents a novel concept for the integration of closed-circuit reverse osmosis (CCRO) technology and solvent-based precipitation as a means of producing an exceptional quality of water by separating the salts especially chlorides and sulphates from highly saline nanofiltration (NF) rejected stream of the steel industry. The NF rejected stream was extremely concentrated with salts like chloride (1560 mg/L), sulphate (4212 mg/L), manganese (28 mg/L), sodium (418 mg/L) and total dissolved solids (TDS), as high as 8100 mg/L, which are well above the permissible limit for surface discharge. The outcome of this work showed that reverse osmosis (RO) with continuous brine recycling achieved excellent desalination performance. Miscible organic solvents such as diisopropylamine (DIIPA), isopropylamine (IPA), and ethylamine (EA) were found to be effective in precipitating chloride and sulphate ions from highly concentrated RO brine. The overall removal efficiency of sulphate and chloride was found to be 99.88% and 91%, respectively. Preliminary treatment cost was estimated and found to be around 7.35 $/m3. The treated water can either be recycled in the system or safely released into the environment. The readers of this research article will be benefitted by gaining a thorough understanding of the treatment of concentrated brine from nanofiltration using an integrated RO-precipitation technique.

Aqueous miscible organic solvent treated NiTi layered double hydroxide De-NOx photocatalysts

New efficient photocatalysts are required to remediate polluted urban atmospheres. We prepared a series of highly dispersed aqueous miscible organic (AMO) solvent treated NiTi layered double hydroxide (NixTi-AMO-LDHs (x = 2,3)) and studied their performance in the photocatalytic abatement of NOx gases. These photocatalysts can be prepared by a simple and scalable coprecipitation method at room temperature. NixTi-AMO-LDHs (x = 2,3) have been prepared with specific N2 BET surface areas and pore volumes up to to 492 m2g−1 and 1.37 cm3 g−1 respectively. Under sunlight simulation, the De-NOx performance of the conventional LDH and P25 (TiO2) benchmarks were surpassed by 40% and 17% respectively by the NixTi-AMO-LDHs. The NixTi-AMO-LDHs photocatalyst also exhibited outstanding reusability and unusually low release of the toxic NO2. The selectivity for the De-NOx process was investigated by in situ DRIFT measurements, the high surface area and pore volume was observed to play a significant role on the adsorption of the NO2 and N2O4 intermediates. The 2D character of the AMO-LDHs contributed to an enhancement in the production of radical species under illumination and reduction charge carrier recombination.

Formation of micro/nanoparticles and microspheres from polyesters by dispersion ring‐opening polymerization

AbstractThe micro/nanoparticles and microspheres of polyesters derived from the heterocyclic monomers of lactide (L,L or D,L), ε‐caprolactone, and glycolide have received significant interest as drug carriers for biomedical applications. This review focuses on the recent advances in the study of polyester‐based micro/nanoparticles and microspheres derived from the dispersion ring‐opening polymerization (ROP) of heterocyclic monomers, and/or self‐assembly of polyester macromolecules, and/or dialysis of polyester solution in water‐miscible organic solvents against water. The dispersion polymerization of heterocyclic monomers in the presence of non‐polar miscible solvents and amphiphilic polymer surfactant leads to the formation of polyester particles with a narrower size distribution. The use of the polymer surfactant is crucial in controlling the diameter, morphology, and stability of the polyester particles formed during the ROP. The polymer surfactant acts as a stabilizer and is bound to the polyester particles strongly and irreversibly to control the size and morphology of polyester microspheres. The properties of polyester particles are varied by controlling the number average diameter and diameter polydispersity index. Hence, in this article, we review different synthetic strategies developed for the formation of polyester based particles with controlled diameter of distribution and the factors influencing its formation such as structure of the polymer surfactant, critical micelle concentration of the surfactant, type of radical initiator/monomer used, reaction parameters, etc. The article also describes methods developed for transforming the polyester microspheres into the water for better biocompatibility and encapsulation of bioactive compounds, drugs, and proteins into the polyester particles and their potential release at the targeted specific site are reviewed.

Quantitation of Conjugation-related Residual Solvents in Antibody Drug Conjugates using Headspace Gas Chromatography

Background: Antibody Drug Conjugates (ADCs) are complex hybrid molecules comprised of a monoclonal antibody (mAb) connected to a small molecule drug through a linker. The key step in the production of ADCs is bringing together the protein in an aqueous buffer with a hydrophobic small molecule in order to achieve conjugation of the molecules. This step involves dissolving the small molecule portion of the compound in an aqueous miscible organic solvent. These solvents and unconjugated small molecules are ideally cleared by downstream processing in order to achieve the desired product quality. As part of the control system to ensure product quality, the determination of residual solvents in pharmaceuticals is of significant importance in order to protect patient safety and ensure an efficacious drug. Objective: Headspace gas chromatography (HS-GC) is the most widely used tool for quantification of residual solvents for small molecule active pharmaceutical ingredients (APIs) but is not widely used for the analysis of protein-containing samples. In this study, the detection of residual solvents in headspace injections was explored using various conditions in order to detect commonly used conjugation solvents including N,N-dimethylacetamide (DMA), N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), Ethylene Glycol (EG), and Propylene Glycol (PG) in an ADC drug product sample. Methods: Various organic solvents were explored to enhance the response observed with complex protein and residual solvent matrixes. As EG and PG do not partition into the headspace efficiently in the ADC drug product samples that contain large amounts of water, ionic liquids and other ionic compounds were screened with the ADC samples to see if they could improve the partitioning of the key solvents EG and PG. Results: Following headspace and chromatographic optimization, we have developed an approach for the detection and quantification of several conjugation reaction solvents in ADC samples. Conclusion: This new approach is an HS-GC method that simplifies Gas Chromatography (GC) analysis and sample preparation and can be readily implemented in quality control testing for bioconjugated products.

Prediction of hypothetical solubility of drugs in phase separated miscible binary solvent mixtures using an interpolation technique

Solubility is one of the most important thermodynamic properties in drug discovery, and a major parameter to be considered in pharmaceutics in order to achieve suitable formulations for the desired pharmacological response. It is also an impotant issue in drug re-crystalization and drug extraction using liquid–liquid phase separation. So, the knowledge of solubility in the neat and mixed solvents at various temperatures is neccesary in many pharmaceutical/chemical areas. However, the experimental measurement of this property in all mixture compositions and temperatures is not possible; for example, due to phase separation. In the current study, the applicability of the Jouyban-Acree based models will be investigated for prediction of solubility data in such a solvent mixture using an interpolation technique that provides hypothetical solubility data for these troubled fractions.