Residual Solvent Research Articles

Precision-aiming tuning of membranes prepared by NIPS and its performance enhancement

An industrially developed non-solvent induced phase separation (NIPS) for porous membranes is still being studied to improve performances and expand application fields. The work introduces a novel strategy to tune the structures of porous membranes via the combination of glass transition temperatures (T g ) and external stimulations . T g was adjusted by the content of residual solvents and additives. Heat and air blowing for higher T g porous membranes than 100 °C were efficient strategies to improve the surface porosity to 65%, the water flux to 600 LMH/bar, and the BSA rejection to 99.8%. Heat and vacuum for lower T g membranes than 100 °C could melt the surface pores and becomes a pier-like structure with the water flux of 2.4 LMH/bar and Na 2 SO 4 rejection of 95.6%. The method could hold great potential for achievable tuning of main characteristic parameters such as structure, performance, porosity, pore size, and molecular weight cut-off.

Modeling Multiphase Heat and Mass Transfer in an Agitated Filter Dryer by Integrating Experiment, Computations, and Analytical Solutions.

The drying of a wet cake consisting of an active pharmaceutical ingredient and solvent in an agitated filter-dryer is a critical and challenging unit operation in the pharmaceutical industry. The complexity of this operation is attributed to the constraints on product quality in terms of its physical properties in addition to the residual solvent content. In this manuscript, a better understanding of the drying mechanism is gained by integrating insights from three-dimensional analytical solutions and computational fluid dynamics simulations into a zero-dimensional model to explain experimental data. The approach provides the time evolution of the mass flow rate of solvent from the wet cake and the center-point temperature of the cake with good accuracy. Further investigation of the zero-dimensional model reveals important parameters such as the mass transfer rate number that predicts whether the process is convection-controlled or diffusion-controlled, and the thermal load of vaporization that estimates the fraction of solvent vaporized per unit time. These parameters can be useful in devising a drying protocol for agitated-filter dryers.

Quantitative determination content for the Residual Organic Solvents in a combined drug based on Jacob's Ladder herbs, motherwort herbs and hawthorn fruit by GC- FID

The article presents quantitative determination content for the residual organic solvents in a combined herbal medicine based on motherwort herb (Herba Leonuri), hawthorn fruits (Crataegus spp.) and jacob’s ladder herb (Polemonium caeruleum L.), by the use of Gas Chromatography (GC) accompanied by Flame Ionization Detector (FID). In accordance to the requirements of Russia State pharmacopoeia 14th edition, General Pharmacopoeia Monograph 1.1.0008.15 "Residual organic solvents" and 1.2.1.2.0004.15 "Gas chromatography", the measurement of residual solvents is mandatory. You can now take advantage of GC equipment with faster temperature changes combined with shorter GC capillary columns to achieve significant efficiency gains and faster analysis times. In the present study, using a flame ionization detector, a gas chromatographic method for determining the residual levels of ethanol in a combined herbal medicine based on motherwort herb, hawthorn fruit and jacob’s ladder herb was tested, and the separation was performed on a column ZB-624 (G43 6% cyanopropylphenyl 94% dimethylpolysiloxane) using Agilent 7890А, with installation for Head Space analysis Agilent 7694Е, USA, Agilent. The retention time of standard ethanol was 7.09 minutes. It resulted that the linearity for ethanol is between 10-150% of the rated content. The method was approved in accordance with Russia State pharmacopoeia 14th edition, General Pharmacopoeia Monograph 1.1.0012.15 "Validation of analytical methods". The described method is simple, sensitive, durable, reliable and reproducible for determining the quantitative content for the residual organic solvents in a combined herbal medicine based on motherwort herb, hawthorn fruits and jacob’s ladder herb.

Design and optimization of gatifloxacin loaded polyvinyl alcohol nanofiber for the treatment of dry eye infection: In vitro and in vivo evaluation

According to a clinical report, nearly 50% of dry eye patients have an elevated risk of ocular infections and inflammations. Nanofiber could serve as a potential vehicle for treating anterior ocular disease because of its sterile nature, known solubility enhancing ability, capacity to carry multiple drugs, and controlled drug release capability, which can minimize overall dose and dosing frequency. As a result, the goal of this study was to assess the therapeutic potential of Gatifloxacin (GAF) loaded Polyvinyl alcohol (PVA) nanofiber for the treatment of dry eye syndrome with infection. Towards in vitro assessment, optimized nanofiber was characterized through surface imaging, swelling, release behavior, sterility, residual solvent, and degradation studies. Goat cornea was used to determine trans corneal penetrability. Therapeutic performance of the optimized nanofibers was assessed in a dry eye animal model. Results showed that applied potential of 12 kV, the flow rate of 3 μl/min, and plate to collector distance of 20 cm were the optimized electrospinning parameters for bead-free uniform fiber of around 200 nm. Longer precorneal contact time and biphasic release behavior, with an initial burst phase followed by a 7-h controlled release profile, are thought to reduce the need for frequent dosing to manage dry eye issues. Additionally, there was partial tear volume restitution and the tear ferns revival after 36h. Overall, the in-vitro and in-vivo results suggested that the developed product could be a viable alternative to manage dry eye infectious syndrome with less frequent dosing.

Betulin Self‐Assembly: From High Axial Aspect Crystals to Hedgehog Suprastructures

AbstractBetulin is introduced as a building block of supramolecular structures that form by noncovalent interactions. Betulin, an abundant triterpene, is first extracted from birch bark to self‐assemble into hierarchical crystalline structures. Following a direct bottom‐up process, solvatomorphs of betulin‐2‐propanol form high axial aspect microparticles, 100–300 µm in length, and lateral sizes in the 15–40 µm range. Under sonication, the microparticles evolve into 3D hedgehog suprastructures (15–30 µm in size) comprising a core (3–5 µm diameter) with connected spines (200–300 nm in width). Depending on the intensity of the delivered energy, the associated morphogenesis starts with metastable aggregates that undergo dislocation, solvent migration, and radial growth. It is found that the formed spherulite‐like, hedgehog structures are a consequence of residual solvent diffusion, leading to crystallites with oriented attachment on specific planes. These results add to the design of structures from natural building blocks, which are expected to deliver functions encoded in the respective morphology. Owing to the unique features of betulin supraparticles, they develop surface architectures, for instance, in superhydrophobic coatings, which are shown to exhibit exceptional repellency and surface mechanical strength, as tested on various substrates.

Self-organized ensembles of nematic domains in magnetic and electric fields.

The structural and magneto- and electro-optical properties of a self-organized ensemble of nematic domains formed on a polycarbonate film in the presence of a residual solvent are studied. The film covered one of the plane-parallel glass plates of a liquid crystal cell. The magnetic field stabilizing the planar alignment of the liquid crystal was applied parallel to the cell surfaces and the reorienting electric field, perpendicular to them. The voltage dependences of the intensity of light transmitted through the domain ensemble were obtained at different constant values of the magnetic field. The comparison of the experimental dependences with the dependences calculated using the liquid crystal free-energy minimization procedure has shown good agreement between them. The mutual effect of structural elements of the ensemble and the effects of phase modulation of light are analyzed by comparing the structural, magnetic, and electric coherence lengths.

Lipid nanodiscs of poly(styrene-alt-maleic acid) to enhance plant antioxidant extraction

Abstract Plant antioxidants can be applied in the management of various human diseases. Despite these, extraction of these compounds still suffers from residual solvent impurities, low recovery yields, and the risks of undesirable chemical changes. Inspired by the protein–lipid interactions in the cell membranes, we proposed using poly(styrene-alt-maleic acid) (PSMA) to destabilize and associate with the bilayer lipids into the membrane-like nanodiscs. Such nanostructures could serve as protective reservoirs for the active compounds to reside with preserved bioactivities. This concept was demonstrated in the antioxidant extraction from robusta coffee leaves. Results indicated that aqueous PSMA extraction (no buffer agent) yielded products with the highest contents of phenolic acids (11.6 mg GAE·g−1) and flavonoids (9.6 mg CE·g−1). They also showed the highest antioxidant activity (IC50 = 3.7 µg·mL−1) compared to those obtained by typical sodium dodecyl sulfate and water extraction. This biomimetic approach could be considered for developing environmentally friendly extraction protocols in the future.

Sonication Impacts and Sonolytic Pathways for Some Organic Solvents Used in Pharmaceutical Analyses

In pharmaceutical residual solvents analyses, some organic solvents are generally used as sample diluents (or sample solvents) (1–4). Interferences from sample diluents should be monitored in method development and routine use. Gas chromatography (GC) is the technique that is widely used for testing gaseous or volatile substances.

Estimation of Nine Organic Volatile Impurities in Bulk Dapagliflozin propandiol hydrate and Dosage forms from different sources using a new developed HS-GC-FID method

As a part of impurity profiling, we aimed in this work to determine the content of organic volatile impurities (OVIs), commonly known as residual solvents (RSs), in different sources of dapagliflozin propandiol monohydrate as raw materials and marketed film-coated tablets. For that, a novel HS-GC-FID method has been developed and validated for determination of methanol, ethanol, ether, acetonitrile, dichloromethane, n-hexane, ethyl acetate, tetrahydrofuran and toluene. Dimethyl sulfoxide DMSO was used us diluent. The separation was achieved on Agilent DB-624 (30m, 0.530mm, 3.0µm) column and nitrogen as carrier gas with a total run time of 20 minutes. Solvents peaks indicate high resolution. Correlation factor R2 was estimated for each solvent and values ranged from 0.9990 to 0.9995. Estimation of limit of detection of these nine solvents showed that developed method was more sensitive than published method. The percentage recoveries calculated and the values ranged from 100.2% to 111.54%. The methods has been found to be simple, very sensitive, rugged, reliable and reproducible for the quantitation of these solvents in different sample of dapagliflozin raw materials and marketed tablets. Ethanol (class 3) and n-hexane (class 2) were detected in unacceptable level in some marketed samples.

Green solvents, potential alternatives for petroleum based products in food processing industries

Solvent extraction is used at the industrial scale for extraction of oil, flavouring and functional compounds from the source materials. Easy availability at lower price makes petroleum based solvents (e.g., hexane, petroleum ether, etc.) the preferred choice for solvent extraction. However, some amount of the solvent always escapes to the environment during the extraction process and the yield product also contains some amount of residual solvent. This causes hazard not only to the environment and people at large, but also affects the manpower involved in the solvent extraction industry in particular. This has led to the search of alternative solvents which have lower toxicity and are environmentally safe. Green solvents appear to be a potential candidate for this. Solvent extraction studies performed using green solvents have revealed their equal or higher extraction efficacy to that of petroleum based products. This review paper aims to provide comprehensive information about the studies pertaining to the application of green solvents as a safer and their potential for replacement of petroleum based solvents for extraction of fat soluble compounds. In addition, health and environmental aspects of greens solvents along with their associated advantages-disadvantages has also been discussed in this paper.

Phytochemical analysis and evaluation of antioxidant activity of the leaves of Begonia picta smith

Like most other plants begonia picta smith contains various secondary metabolites with great potentials. The aim of this paper is to evaluate the phytochemicals by using quantitative and qualitative analysis of Petroleum ether , Chloroform, Methanol extracts ,with the help of standard methods as well solvent residual analysis byGCHS The findings from quantification and phytochemical screening showed the presence of alkaloids, flavonoids, reducing sugars, Phenols, proteins, amino acids, saponins, tannins, terpenoids,Antioxidant activity was determined by 1, 1-diphenyl-2-picryl hydrazyl (DPPH)scavenging method, nitric oxide scavenging method, reducing power assay method and Inhibitory concentrations (IC50) were calculated. the residual solvents present in the three herbal extract also in current specified limits. Evaluation of In Vitro Anti-Oxidant activity reveals that methanolic extract is most potent as compare to other extracts by taking Ascorbic acid as standard. This information clearly represent that the plant Begonia picta smith is the good source of dietary antioxidant.

Scalable fabrication of Solvent‐Free composite solid electrolyte by a continuous Thermal-Extrusion process

Composite solid-state electrolytes (CSEs) are regarded as a promising alternative for the next‐generation lithium-ion batteries because they integrate the advantages of inorganic electrolytes and organic electrolytes. However, there are two issues faced by current CSEs: 1) a green and feasible approach to prepare CSEs in large scales is desired; and 2) the trace solvents, remaining from the preparation processes, lead to some serious concerns, such as safety hazard issues, electrolyte–electrode interfacial issues, and reduced durability of batteries. Here, a continuous thermal-extrusion process is presented to realize the large-scale fabrication of solvent‐free CSE. A 38.7-meter CSE membrane was prepared as a demonstration in this study. Thanks to the elimination of residual solvents, the electrolyte membrane exhibited a high tensile strength of 3.85 MPa, satisfactory lithium transference number (0.495), and excellent electrochemical stability (5.15 V). Excellent long-term stability was demonstrated by operating the symmetric lithium cell at a stable current density of 0.1 mA cm−2 for over 3700 h. Solvent-free CSE lithium metal batteries showed a discharge capacity of 155.7 – 25.17 mAh g−1 at 0.1 – 2.0C, and the discharge capacity remained 78.1% after testing for 380cycles.

ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR ESTIMATION OF RESIDUAL SOLVENTS IN GLICLAZIDE USING GAS CHROMATOGRAPHY

Objective: The present work discusses developing a novel method for estimation of residual solvents in Gliclazide using Gas chromatography and determining its consistency, reliability and reproducibility by performing its validation.
 Methods: A Gas chromatograph equipped with aflame ionization detector, column DB-624 (60 m x 0.32 mm x 1.8 µm) with Nitrogen as carrier gas was used and the column temperature was 40 °C (hold for 15 min) and increased to 240 °C at 20 °C per min. The solutions were prepared using-Methyl-2-Pyrrolidone (NMP) diluent as per the procedure given in protocol and appropriately injected as per the sequence. The validation parameters checked were System suitability, Specificity, Linearity and Range, Accuracy, Precision, Limit of detection, Limit of quantitation, Ruggedness and Robustness.
 Results: The data for each validation parameter tested is compiled and documented. It was found that the results obtained for each parameter compiled with their given acceptance criteria. Hence, the developed method was considered reproducible, reliable and consistent.
 Conclusion: The method of analysis complies with all the parameters tested and it was found to be reliable, consistent and reproducible.

Insights into the Origins of Minority Carrier Traps in Solution‐Processed Organic Semiconductors and Their Effects on Transistor Photostability

AbstractMinority carrier traps in the bandgap of organic semiconductors (OSCs) are pervasive and of vital importance in determining the performance and stability of the optoelectronic device. Understanding their origins is one critical issue at both the fundamental and applied levels. However, relevant research has rarely been performed due to the lack of an effective strategy for quantitatively assessing the minority carrier traps buried in OSCs. Here, organic field‐effect transistors (OFETs) operated under strong and long‐term light illumination can be used as a model device to assess the amount of minority carrier traps in solution‐processed OSCs, are proposed. Based on the experimental results and theoretical calculations, first identified hydrated impurities (water and oxygen) in the residual organic solvents primarily contribute to formation of minority carrier traps within the OSC bandgap, giving rise to photo‐induced electrical instability of OFETs. To address this problem, a molecular additive strategy is developed to improve the OFET photostability by releasing trapped electrons from the levels of minority carrier traps. This work not only elucidates the significant role of water and oxygen in the residual organic solvents in forming minority carrier traps but also provides guidelines for improving OFET photostability for practical applications.

Combination of headspace solid phase extraction with lighter than water organic solvent-based dispersive liquid-liquid microextraction for the extraction of residual solvents from herbal laxative medicine prior to gas chromatography-flame ionization detection

Combination of headspace solid phase extraction with lighter than water organic solvent-based dispersive liquid-liquid microextraction for the extraction of residual solvents from herbal laxative medicine prior to gas chromatography-flame ionization detection

Assessment of AlphaFold2 for Human Proteins via Residue Solvent Exposure.

As only 35% of human proteins feature (often partial) PDB structures, the protein structure prediction tool AlphaFold2 (AF2) could have massive impact on human biology and medicine fields, making independent benchmarks of interest. We studied AF2's ability to describe the backbone solvent exposure as a functionally important and easily interpretable "natural coordinate" of protein conformation, using human proteins as test case. After screening for appropriate comparative sets, we matched 1818 human proteins predicted by AF2 against 7585 unique experimental PDBs, and after curation for sequence overlap, we assessed 1264 comparative pairs comprising 115 unique AF2 structures and 652 unique experimental structures. AF2 performed markedly worse for multimers, whereas ligands, cofactors, and experimental resolution were interestingly not very important for performance. AF2 performed excellently for monomer proteins. Challenges relating to specific groups of residues and multimers were analyzed. We identified larger deviations for lower-confidence scores (pLDDT), and exposed residues and polar residues (e.g., Asp, Glu, Asn) being less accurately described than hydrophobic residues. Proline conformations were the hardest to predict, probably due to a common location in dynamic solvent-accessible parts. In summary, using solvent exposure as a metric, we quantified the performance of AF2 for human proteins and provided estimates of the expected agreement as a function of ligand presence, multimer/monomer status, local residue solvent exposure, pLDDT, and amino acid type. Overall performance was found to be excellent.

A Novel Analytical Method for the Determination of Residual Solvents in Mesalamine Delayed Release Tablets by GC-HS Method

Background: Residual solvents and organic volatile impurities are monitored using Head Space Gas Chromatography present in pharmaceutical samples. Mesalamine is a 5-aminosalicylic acid 5-ASA based agent which is used to treat adults with ulcerative colitis. 
 Objective: In this study, an attempt was made to analyze the residual organic solvents such as isopropyl alcohol and dichloromethane present in Mesalamine Delayed-Release Tablets by headspace gas chromatography (HS-GC). 
 Method: The carrier gas streamed was nitrogen, the method was developed and optimized by using a DB-624(60 m × 0.53 mm × 3.0 µm) column coupled with a flame ionization detector. A capillary column consisting of 6 % cyanopropylphenyl - 94 % dimethyl polysiloxane was employed as the stationary phase. An injector temperature of 200°C was programmed to prevent degradation. 
 Results: A temperature of 40°C was set as the initial oven temperature for a period of 10 min and set at a rate of 20°C min−1 and monitored at a final temperature of 220°C for 5 min. Chloroform and N, N-dimethylacetamide was selected as the sample solvent. The validation studies were performed with regard to International Council for Harmonization (ICH) Q2 guidelines for the validation of analytical experiments. 
 Conclusion: All the validation parameters complied with the acceptance criteria. Hence, the optimized method developed and validated can be utilized for the concurrent estimation of residual solvents in tablet formulations.

Correction to: High-Throughput GC-FID Method for the Determination of Residual Solvents in Early-Phase Drug Discovery Samples

Correction to: High-Throughput GC-FID Method for the Determination of Residual Solvents in Early-Phase Drug Discovery Samples

Dual-Resistance of Ion Migration and Moisture Erosion via Hydrolytic Crosslinking of Siloxane Functionalized Poly(Ionic Liquids) for Efficient and Stable Perovskite Solar Cells

Dual-Resistance of Ion Migration and Moisture Erosion via Hydrolytic Crosslinking of Siloxane Functionalized Poly(Ionic Liquids) for Efficient and Stable Perovskite Solar Cells

Effect of Solvent Residue in the Thin-Film Fabrication on Perovskite Solar Cell Performance.

Organic-inorganic Pb-based halide perovskite photoelectrical materials, especially perovskite solar cells (PSCs), have attracted attention due to the significant efforts in improving the power conversion efficiency (PCE) to above 25%. However, the stability issue of the PSCs restricts their further development for commercialization. Strategies are designed to keep moisture and oxygen out of the perovskite films, such as additive, surface passivation, and solvent engineering; however, usually, the corrosion of active films by the residual solvent is mostly ignored. Solvent residue is the paramount factor influencing the stability of the perovskite film prepared by the solution method, and most solvents can be easily absorbed and accelerate the perovskite film decomposition. Here, we studied the residual solvent effect on two kinds of perovskite films obtained by different annealing processes: hot air annealing and hot bench annealing. Several detection techniques were used to study the performance of two different annealing methods, including time-of-flight secondary ion mass spectrometry (ToF-SIMS), thermogravimetric analysis (TGA), and field-emission scanning electron microscopy (FESEM). The perovskite film obtained by hot air annealing shows less residual solvent and better device performance than the hot bench annealing method. This method is expected to provide insight into reducing solvent residue to improve the stability of the PSCs, especially for future commercialization.