Solvent-free Production Research Articles

Alkylsulfonic acid functionalized aluminoborate: A highly efficient and regioselective solid acid catalyst for ring-opening addition of epoxide under solvent-free condition

Functionalized solid acid material has more accessible active surface and therefore is usually considered as an important substitute for conventional liquid mineral acid. In this work, a novel alkylsulfonic acid functionalized porous aluminoborate molecular sieve (PKU-1) has been prepared through 3-step post-synthetic method, and the high-density acidic sites were tailored and comprehensively characterized by various measurements. These acidity-controllable active sites exhibit high activity and specific regioselectivity towards alcoholysis reaction for the solvent-free production of methoxyl alcohol, and turnover frequency reaches ∼1000 h–1, which is much superior to previous reports. Comprehensive characterizations indicate catalytic centers exclusively come from –SO3H acid sites, rather than other type of Brönsted or Lewis acid sites. A plausible reaction mechanism was proposed to interpret the key role of –SO3H active sites on alcoholysis reaction based on the related experimental results. This work offers a promising solution to generate the controllable acidity and provides an available candidate in the environmentally benign catalysis for selective synthesis of some value-added compounds.

Establishment of a semi-continuous nano-production line using the Microfluidizer® technology for the fabrication of lipid-based nanoparticles part 1: Screening of critical parameters and design of experiment optimization studies

A variety of strategies for producing high-quality nanoparticles have been reported in recent years. Batch-based bottom-up and top-down technologies are generally the most efficient methods, but present a number of challenges, particularly in terms of variability, safety, sustainability and large-scale production. In this study, a scalable, semi-continuous production line was built by connecting individual processing units, including a high shear mixing device, the Microfluidizer® technology and a cooling system. Each unit was equipped with an adequate temperature control to allow solvent-free production of solid lipid nanoparticles (consisting of Precirol® ATO 5 or Gelucire® 43/01) and nanostructured lipid carriers (additionally comprising Labrafac™ lipophile WL 1349). Subsequently, critical formulation parameters and critical process parameters (CPPs) of the individual processing units and their effects on particle size (i.e., critical quality attribute (CQA)) were investigated to identify appropriate input parameters for the subsequent Design of Experiment (DoE) studies conducted after linking the process units to a semi-continuous production line. For particle size monitoring, spatially resolved dynamic light scattering (SR-DLS) measurements were conducted and compared to standard DLS measurements to evaluate the applicability of SR-DLS as an inline monitoring tool. It was found that matrix composition, emulsifier concentration, pressure and number of cycles when processing through Microfluidizer® processor were the most influencing parameters. By optimizing these parameters, five-times higher throughputs could be achieved by the semi-continuous manufacturing line. In addition, the particle size measurements with SR-DLS confirmed the feasibility of implementing this technology for real-time particle size monitoring as an important safety factor in quality control.

Solvent-Free Production of High-Value Amphipathic Esters Derived from Byproduct Streams of Biomass Processing

Solvent-Free Production of High-Value Amphipathic Esters Derived from Byproduct Streams of Biomass Processing

Influence of Screw Design and Process Parameters on the Product Quality of PEO:LiTFSI Solid Electrolytes Using Solvent-Free Melt Extrusion

All-solid-state battery (ASSB) technology is a new energy system that reduces the safety concerns and improves the battery performance of conventional lithium-ion batteries (LIB). The increasing demand for such new energy systems makes the transition from laboratory scale production of ASSB components to larger scale essential. Therefore, this study investigates the dry extrusion of poly(ethylene oxide):lithium bis (trifluoromethylsulfonyl)imide (PEO:LiTFSI) all-solid-state electrolytes at a ratio of 20:1 (EO:Li). We investigated the influence of different extruder setups on the product quality. For this purpose, different screw designs consisting of conveying, kneading and mixing elements are evaluated. To do so, a completely dry and solvent-free production of PEO:LiTFSI electrolytes using a co-rotating, intermeshing, twin-screw extruder under an inert condition was successfully carried out. The experiments showed that the screw design consisting of kneading elements gives the best results in terms of process stability and homogeneous mixing of the electrolyte components. Electrochemical impedance spectroscopy was used to determine the lithium-ion conductivity. All electrolytes produced had an ionic conductivity (σionic) of (1.1–1.8) × 10−4 S cm−1 at 80 °C.

Influence of Extruder Setup and Process Parameters on the Product Quality of Solid Polymer Electrolytes Using Melt Extrusion

All solid-state batteries (ASSBs) are the next generation battery technology, in which the classical liquid electrolyte is replaced by an ion-conducting solid electrolyte. Materials that are used as solid-state electrolytes are generally divided into three material classes: polymers, oxides and sulphides. Electrolyte materials for ASSBs have been extensively studied regarding their electrochemical performance and their stability towards the electrode materials. Nevertheless, the commercialization of ASSBs is still hindered by the material availability in case of oxide and sulphides and the knowledge of scaled production routes for all kinds of separators. Polymers are readily available on the global market. It is thus possible to focus more on the processing routes of polymer based solid electrolytes. The use of thermoplastics as matrix for solid electrolytes (SE) offers the prospect of facile upscaling of the process from lab-scale to industrial series production by the implementation of a solvent-free thermal extrusion process. A twin-screw extruder offers the possibility of continuously mixing the SE components to produce homogeneous polymer based SEs. With two feeding units, the addition of the components takes place separately. This eliminates the time-consuming premixing step to obtain a homogeneous mixture.Thermoplastic poly(ethylene oxide) (PEO) is one of the most investigated materials for polymer based SEs due to its capability to dissolve alkali salts like Lithium(bistrifluoromethanesulfonyl)imide (LiTFSI). The thermal process route of PEO and its effect on the polymeric properties are currently under investigation. Previous works from our research group show that the processability of PEO not only depends on the conductive salt (LiTFSI), but also on its molecular weight and applied process parameters. [1] With increasing molecular weight, PEO becomes more sensitive towards thermal and mechanical load that leads to chain scissoring and degradation even at small load. Hence, the use of low molecular weight PEO (Mw= 100.000 g mol-1) is preferable for the dry production of PEO based SEs.The aim of this work is to optimize the extrusion process using a co-rotating twin-screw extruder for the solvent free production of solid PEO/LiTFSI-electrolytes in a molar ratio of 20:1 (EO:Li). Here, we investigate the effects of several extruder set-ups on the mixing behaviour of PEO and LiTFSI. Therefore, type of dosing and screw design are varied. The screw can be designed with conveying, kneading and mixing elements. We compare the dry extrusion of a premixed PEO/LiTFSI (20:1) batch with dry extrusion of PEO/LiTFSI (20:1) using two feeding units, one for each component. Process parameters, such as pressure at the extruder die, actual screw speed, torque and barrel temperature are continuously measured during the production. Process temperature and screw speed are optimized to avoid degradation of PEO. PEO/LiTFSI-electrolytes are produced with a process temperature of 90 °C across the whole extruder barrel and with screw speeds of 5 – 15 rpm. The products are evaluated by their homogeneity and quality of the extruded electrolytes. Optical microscopy is used for macroscopic evaluation and the Li-salt distribution is checked with SEM/EDX. Conductivity and rheology measurements are performed to determine the lithium concentration within the electrolyte and loss of molecular weight, respectively. For the determination of the ionic conductivity, we examine electrochemical impedance spectroscopy (EIS). The characterization of the extruded electrolytes helps to find optimal process parameters for the production of polymer based SEs.

Desolvation Processes in Channel Solvates of Niclosamide.

The antiparasitic drug niclosamide (NCL) is notable for its ability to crystallize in multiple 1:1 channel solvate forms, none of which are isostructural. Here, using a combination of time-resolved synchrotron powder X-ray diffraction and thermogravimetry, the process-induced desolvation mechanisms of methanol and acetonitrile solvates are investigated. Structural changes in both solvates follow a complicated molecular-level trajectory characterized by a sudden shift in lattice parameters several degrees below the temperature where the desolvated phase first appears. Model fitting of kinetic data obtained under isothermal heating conditions suggests that the desolvation is rate-limited by the nucleation of the solvent-free product. The desolvation pathways identified in these systems stand in contrast to previous investigations of the NCL channel hydrate, where water loss by diffusion initially yields an anhydrous isomorph that converts to the thermodynamic polymorph at significantly higher temperatures. Taking the view that each solvate lattice is a unique "pre-organized" precursor, a comparison of the pathways from different starting topologies to the same final product provides the opportunity to reevaluate assumptions of how various factors (e.g., solvent binding strength, density) influence solid-state desolvation processes.

Potential of Supercritical Acrocomia aculeata Oil and Its Technology Trends

This study discusses the bioactive composition, supercritical extraction, and biological activity of Acrocomia aculeata in publications in the last ten years. Numerous compounds have been identified in A. aculeata, which include fatty acids, carotenoids, phenolic compounds, and tocopherols, discussed in this article. Although there are several studies with the fruit using conventional extraction to obtain oil, there are only a few involving extraction at high pressures. Therefore, this article emphasized the potential of extraction with supercritical fluid (SFC) to obtain oil due to its good selectivity, fractions distributed in terms of mass yield, and chemical composition of the obtained extracts, which provides a solvent-free product, making it safe for application in the food industry. The biological activity of A. aculeata extracts was also discussed, including antidiabetic, anti-inflammatory, diuretic, antimicrobial, antioxidant, neuroprotective, and photoprotective effects, which can produce effects on human health. This review produces important results that can act as a basis for future studies related to obtaining bioactive compounds from A. aculeata with a high degree of purity and good quality in its applications.

Green heterogeneous catalysts for cleaner solvent-free production of acetates

The development of new chemical synthetic methodologies that transform industrial chemical processes into more sustainable ones, constitutes one of the challenges and objectives of chemical research both in academia and in industry. The use of activated carbons as heterogeneous catalysts represents one of the most beneficial options for process efficiency in terms of reaction rate, yield, and ease of work-up. We have produced six new activated carbons by treatment of three affordable commercial carbons with either nitric acid, or with sulfuric acid. The complete characterization of these nine activated carbons has been carried out through the measurement of nitrogen adsorption capacity, porosimetry, elemental organic analysis, X-ray photoelectron spectroscopy, scanning electron microscopy and determination of the point of zero charge; transmission electron microscopy was also performed on two of them. The catalytic activity of these nine catalysts has been tested in the acetylation reaction of hydroxyl groups, undoubtedly one of the most versatile and widely used chemical transformations both at the laboratory and industrial scale. The results show that by means of a simple and affordable modification of commercial xerogel with sulfuric acid, a more efficient catalyst is formed. Acetylation with the best catalyst is completed in 90 min at room temperature and the product is easily isolated in quantitative yield. The system can be reutilized for five runs with only a small loss of catalytic activity.

CO2 utilization as gas antisolvent for the pharmaceutical micro and nanoparticle production: A review

A reduction in particle size improves the solubility and bioavailability of pharmaceuticals. The traditional methods utilized in this regard are associated with problems so the use of supercritical fluid has been highlighted in recent decades. To prepare nanoparticles by employing the gas antisolvent (GAS) technique, a specific amount of solution (solute dissolved in organic solvent) was loaded into a cell in the oven. The supercritical carbon dioxide was injected and dissolved into the organic solvent. Therefore, volume expansion occurred and the solute was precipitated with a new particle size distribution on the filter at the end of the cell. This technique exhibits advantages such as particle size control, solvent-free product, and low-temperature process. Many experimental and modeling research has been conducted to synthesize nano- and microparticles based on the GAS process. The present study seeks to review the effective factors and literature on the GAS technique. All parameters affecting the GAS process including pressure, temperature, antisolvent addition rate, initial soluble concentration, and solvent were investigated. Volume expansion, thermodynamic modeling, and kinetic modeling of the GAS process were reviewed. A comparison was conducted between the advantages and disadvantages of this method with other methods of producing nanoparticles with supercritical fluid.

Solvent-Free Production by Extrusion of Bio-Based Poly(glycerol-co-diacids) Sheets for the Development of Biocompatible and Electroconductive Elastomer Composites.

Faced with growing global demand for new potent, bio-based, biocompatible elastomers, the present study reports the solvent-free production of 13 pure and derived poly(glycerol-co-diacid) composite sheets exclusively using itaconic acid, sebacic acid, and 2,5-furandicarboxylic acid (FDCA) with glycerol. Herein, modified melt polycondensation and Co(II)-catalyzed polytransesterification were employed to produce all exploitable prepolymers, enabling the easy and rapid manufacturing of elastomer sheets by extrusion. Most of our samples were loaded with 4 wt% of various additives such as natural polysaccharides, synthetic polymers, and/or 25 wt% sodium chloride as porogen agents. The removal of unreacted monomers and acidic short oligomers was carried out by means of washing with NaHCO3 aqueous solution, and pH monitoring was conducted until efficient sheet surface neutralization. For each sheet, their surface morphologies were observed by Field-emission microscopy, and DSC was used to confirm their amorphous nature and the impact of the introduction of every additive. The chemical constitution of the materials was monitored by FTIR. Then, cytotoxicity tests were performed for six of our most promising candidates. Finally, we achieved the production of two different types of extrusion-made PGS elastomers loaded with 10 wt% PANI particulates and 4 wt% microcrystalline cellulose for adding potential electroconductivity and stability to the material, respectively. In a preliminary experiment, we showed the effectiveness of these materials as performant, time-dependent electric pH sensors when immersed in a persistent HCl atmosphere.

Cyclodextrin Complexation of Fenofibrate by Co-Grinding Method and Monitoring the Process Using Complementary Analytical Tools.

Solvent-free preparation types for cyclodextrin complexation, such as co-grinding, are technologies desired by the industry. However, in-depth analytical evaluation of the process and detailed characterization of intermediate states of the complexes are still lacking in areas. In our work, we aimed to apply the co-grinding technology and characterize the process. Fenofibrate was used as a model drug and dimethyl-β-cyclodextrin as a complexation excipient. The physical mixture of the two substances was ground for 60 min; meanwhile, samples were taken. A solvent product of the same composition was also prepared. The intermediate samples and the final products were characterized with instrumental analytical tools. The XRPD measurements showed a decrease in the crystallinity of the drug and the DSC results showed the appearance of a new crystal form. Correlation analysis of FTIR spectra suggests a three-step complexation process. In vitro dissolution studies were performed to compare the dissolution properties of the pure drug to the products. Using a solvent-free production method, we succeeded in producing a two-component system with superior solubility properties compared to both the active ingredient and the product prepared by the solvent method. The intermolecular description of complexation was achieved with a detailed analysis of FTIR spectra.

Beta zeolite as an efficient catalyst for the synthesis of diphenolic acid (DPA) from renewable levulinic acid

The solvent-free production of diphenolic acid (DPA) from levulinic acid (LA) and phenol is studied using readily accessible commercial acid zeolites like Beta, ZSM-5 and USY. Acid zeolites are cost-effective catalysts, and they are herein benchmarked against the sulfonic acid resins Amberlyst-15 and Nafion®, and sulfonic acid-functionalized SBA-15 silicas. Beta zeolite with a moderate aluminum content (H-Beta 19, Si/Al=23) presents the best catalytic performance, owing to the right combination of the shape selectivity effect conferred by the BEA structure, and the adequate balance of acidity (Al content and speciation). The optimization of the reaction conditions is tackled by the response surface methodology using as optimization factors the temperature, the PhOH:LA molar ratio, and the catalyst loading. Thus, under the optimized reaction conditions (12 mmol LA, 140 ᵒC, 0.30 g catalyst loading, PhOH:LA = 6:1 mol), over 70% yield to DPA with LA conversion around 77% is obtained after 72 h. Despite the catalyst shows a progressive activity decay in successive uses because of fouling, removal of the formed organic deposits by calcination in air allows restoring the starting catalytic performance.

Mechanism and experimental simulation of non-isothermal melt formation induced by voltage change under auxiliary heating

Over the past few decades, it has been universally acknowledged that melt-electrospinning is an attractive solvent-free production process with the aim of alleviating the solvent-related problems generated by traditional electrospinning techniques. Up to now, the temperature and applied voltage have been considered as the two most important factors affecting the melt-electrospinning process and electrospun fibers. In this paper, an auxiliary heating setup was applied to the melt electrospinning system to deeply understand the effect of heat distribution on the melt-electrospun fibers. Jet motions, morphologies, mechanical properties and inner structures of the fibers obtained under different applied voltage conditions with and without auxiliary heating were investigated. The temperature distribution in melt-electrospinning system was simulated by COMSOL Multiphysics software. The experimental results showed that a higher applied voltage results in a smaller fiber diameter, more disordered fiber mat and lower degree of strength with auxiliary heating. The simulation results of the temperature distribution in the spinneret-collector region are in good agreement with the measured values of the infrared images, which proves the feasibility and accuracy of the model.

Preparation of organic-solvent free liposome of Piper albi Linn extract in solution and powder form

Piperine is bioactive alkaloid extracted from white pepper (Piper albi Linn) with several beneficial pharmacological activities. It is also known to enhance the bioavailability of several limited solubilities of other compounds such as curcumin and resveratrol. Nevertheless, due to its poorly water-soluble character, piperine and extract of white pepper are less applied among other plant extracts. Therefore, our research focussed on the engineering of white pepper extract standardized to piperine in liposome solution and liposome powder for further preparation of various pharmaceutical dosage forms.Our research in preparation of extracted white pepper in liposome delivery system successfully prepared spheric liposome solution with 98.92%±1.17% and an average size of 398.7 nm. The liposome was also successfully prepared in dry powder form with sucrose as a carrier for liposome protection. The rehydration is successfully forming a spheric shape with a similar profile to the initial liposome solution. This research paves the way for scalable white pepper extract liposome preparation without the utilization of toxic organic solvent, to produce the commercial solvent-free product in the future.Keywords: Piperine, Piper albi Linn, liposome, extract, organic solvent-free, drug delivery system, spray dry

Solvent-Free Production of ε-Caprolactone from Oxidation of Cyclohexanone Catalyzed by Nitrogen-Doped Carbon Nanotubes

Solvent-Free Production of ε-Caprolactone from Oxidation of Cyclohexanone Catalyzed by Nitrogen-Doped Carbon Nanotubes

Solvent-Free Formation of Cyclodextrin-Based Pseudopolyrotaxanes of Polyethylene Glycol: Kinetic and Structural Aspects.

Pseudopolyrotaxanes (PPRs) are supramolecular structures consisting of macrocycles able to thread on a linear polymer chain in a reversible, non-covalent way, often referred to in the literature as “molecular necklaces”. While the synthesis and reaction mechanisms of these structures in solution have been widely described, their solvent-free production has received little attention, despite the advantages that this route may offer. We propose in this work a kinetic mechanism that describes the PPR formation in the solid phase as a process occurring in two consecutive stages. This mechanism has been used to investigate the spontaneous formation of a PPR that occurs when grinding α-Cyclodextrin (α-CD) with polyethylene glycol (PEG). In the threading stage, the inclusion of the polymer and subsequent release of the water molecules lodged in the cavity of the macrocycle cause vibrational changes that are reflected in the time-dependence of the FTIR-ATR spectra, while the further assembly of PPRs to form crystals produces characteristic reflections in the XRD patterns, due to the channel-like arrangement of CDs, that can be used to track the formation of the adduct in crystalline form. The effects that working variables have on the kinetics of the reaction, such as temperature, feed ratio, molar mass of the polymer and the introduction of an amorphous block in the polymer structure, have been investigated. The rate constants of the threading step increase with the temperature and the activation energy of the process increases at lower proportions of CD to PEG. This is attributed to the lower degree of covering of the polymer chain with CDs that reduces the hydrogen-bonding driven stabilization between adjacent macrocycles. The formation of crystalline PPR, which takes place slowly at room temperature, is markedly promoted at higher temperatures, with lower proportions of CD favoring both the formation and the growth of the crystals. The molar mass of the polymer does not modify the typical channel-like arrangement of packed PPRs but the conversion into crystalline PPR diminishes when using PEG1000 instead of PEG400. At a microscopic level, the crystals arrange into lamellar structures, in the order of hundreds of nm, embedded in an amorphous-like matrix. The introduction of a polypropylene oxide block in the structure of the polymer (Pluronic L62) renders poorer yields and a considerable loss of crystallinity of the product of the reaction. The methodology here proposed can be applied to the general case of inclusion complexes of CDs with drugs in the solid phase, or to multicomponent systems that contain polymers as excipients in pharmaceutical formulations along with CDs.

Organic solvent-free production of colloidally stable spherical lignin nanoparticles at high mass concentrations

Organic solvent-free production of lignin nanoparticles opens a new and scalable route to lignin-based nanogels and other materials.

Lipase-catalyzed two-step esterification for solvent-free production of mixed lauric acid esters with antibacterial and antioxidative activities

Mixed lauric acid esters (MLE) with antibacterial and antioxidative activities were produced through lipase-catalyzed two-step esterification in solvent-free system without purification. In the first reaction, erythorbyl laurate was synthesized for 72 h. Successive reaction for 6 h at molar ratio of 1.0 (lauric acid to glycerol) produced MLE containing erythorbyl laurate and glyceryl laurate with small amounts of residual substrates, by converting 99.52% of lauric acid. MLE addition (0.5–2.0%, w/w) to Tween 20-stabilized emulsions decreased droplet size, polydispersity index, and zeta-potential, possibly enhancing the emulsion stability. In the emulsions, MLE at 0.5 and 2.0% (w/w) caused 4.4–4.6 and 5.9–6.1 log reductions of Gram-positive (Staphylococcus aureus, Listeria monocytogenes) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), respectively, within 12 h. Lipid hydroperoxide concentrations decreased to 50.8–98.3% in the presence of 0.5–2.0% (w/w) MLE. These findings support a novel approach without needing purification to produce multi-functional food additives for emulsion foods.

Lipase catalysed transesterification of palm stearin with ferulic acid in solvent-free media

Recently, several scientific groups investigated the suitable enzymatic route for synthesis of structured phenolic lipids for cosmetic and nutritive purposes. The feruloylated palm stearin (FPS) was obtained from enzymatic transesterification reactions of palm stearin with ferulic acid in solvent-free media with 1 mmol of glycerol or without it, using non-specific lipases, NovoCor ADL (Candida antarctica lipase A); Novozyme435® (Candida antarctica lipase B), and 1,3-specific lipase Lipozyme TL 100L from Thermomyces lanuginosus. The individual lipases and their combinational systems were examined. ESI+-MS/MS confirmed the formation of 19 feruloylated compounds. FPSs were produced by all lipases and their combinations. The positive synergetic effect occurred for 1,3-specific lipase and unspecified lipases with mass ratio 8:2, respectively. The antioxidant activities of all FPSs were examined. FPS produced by NovoCor ADL lipase in presence of free glycerol showed an antioxidant activity 10.3-times higher. In conclusion, the two low-cost lipases NovoCor ADL and Lipozyme TL 100L and its combi-lipase system could be considered suitable low-cost alternative to the expensive wide use N435 lipase in the solvent free production process of FPS for food and cosmetic applications.

Solvent-free production of thermoplastic lignocellulose from wood pulp by reactive extrusion

A novel acylation approach suited to rapid bulk thermoplasticization of lignocellulose without solvents was previously demonstrated by the authors in benchtop batch studies. The method relies upon a benzethonium chloride/sulfuric acid functionalizing agent at low concentrations to act as a wetting agent for the wood pulp, similar to an ionic liquid, yet binds to the lignocellulose ester as a flow aid in the final thermoplastic. The present investigation evaluates the approach in a residence time-limited (45–90 s) continuous twin-screw reactor, where intensive mixing and heat were found to yield high acylation. The modified lignocellulose exhibited desired thermoplasticity by being melt moldable without the need for plasticizers and maintained much of the excellent stiffness of cellulose, demonstrating a maximum flexural modulus of 5.4 GPa and tensile modulus of 1.8 GPa. The influence of extrusion conditions on thermoplasticity was examined by a Design of Experiments (DOE) analysis.