Solvent Removal Research Articles

Sub-50 nm ultra-small organic drug nanosuspension prepared by cavi-precipitation and its brain targeting potential

The purpose of this study was to show whether it is possible to prepare sub 100 nm or preferably sub-50 nm drug nanosuspension (NS) of suitable quality for intravenous administration. Furthermore, we have studied how the brain targeting potential of such small size organic NS differs from relatively bigger size NS. Two combination technologies (cavi-precipitation, H96) and a standard high-pressure homogenization (HPH) technology were used to prepare drug NS of different sizes. The cavi-precipitation process generated the smallest AmB NS, i.e., 27 nm compared to 79 nm by H96 technology and 252 nm by standard HPH technology. Dialysis of the nanosuspension in the original dispersion media was found to be the most efficient solvent removal method without negatively affecting particle size. The removal of organic solvent was found to drastically improve the stability of the formulations. The protein adsorption pattern shows that the small size NS particles obtained by the cavi-precipitation process have the potential to circulate longer in the bloodstream and have the potential to be taken up by the blood–brain barrier. The cavi-precipitation process generated ultrafine NS particles, which fulfilled the quality requirements for intravenous administration and offer a potential solution for brain targeting.

Study on the formation mechanism of isoniazid crystal defects and defect elimination strategy based on ultrasound

In crystallization, crystal growth defects may reduce the strength and purity of crystals, which are not welcomed in the industry. Herein, isoniazid (INH) crystals were chosen as an example to investigate the formation of crystal defects at the molecular scale by combining experiments and molecular dynamics simulations. It was found that the strong interaction between the solvent and the crystal surface, high temperature, small stirring rate, and low supersaturation can lead to more pronounced crystal defects. The bulk severity of INH crystal defects was reflected by N2 adsorption–desorption measurement. Besides, the single-crystal growth experiments manifested the rough growth mechanism for the (110) surface in the axial direction and the stepwise growth mechanism for the (002) surface in the radial direction. For the (110) surface, cavities occurred under the condition where the growth rate of the crystal edges and corners was greater than that of the surface center due to the starvation phenomenon of diffusion. While for the (002) surface, when the solvent removal rate was lower than the solute insertion rate, liquid inclusions were formed, which was verified by Raman microscopy. Furthermore, the ultrasonic strategy was successfully proposed to eliminate INH crystal defects and prepare perfect INH crystals. Moreover, the mechanism of ultrasound to reduce the crystal defect was proposed. We believe this work can provide insights into the design and preparation of defect-free crystals in crystallization.

Elastic, super-hydrophobic and biodegradable chitosan sponges fabricated for oil/water separation

Due to easy availability and biodegradability, chitosan (CS)-based porous adsorbents have attracted significant interest in oil-spill and organic solvent removal. Herein, a multi-network CS-based sponge was fabricated via ion and hydrogen bond cross-linking using lemon, followed by covalent cross-linking via heptanal, in-situ loading of Fe3O4-polydopamine (PDA) particles and polylactic acid (PLA) coating. The as-fabricated sponge was systematically characterized by Fourier transform-infrared spectrometry (FT-IR), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), transmission electron microscope (TEM), static water contact angles (WCA) and so on. The as-fabricated CS-based sponge exhibits excellent elasticity, which could be compressed to large strains (80%) at a relatively high stress (0.685 MPa). The WCA of the targeted sponge can reach to 152.2 ± 1.2º after multiple surface functionalization. In addition, the degradation rate of the as-fabricated sponge can still reach 45.01 ± 1.11% within 15 days. Particularly, the sponge could selectively adsorb oil/organic solvent with up to 50 times of its own weight, and effectively separate the surfactant-stabilized oil-in-water emulsion with a flux of 8753 ± 423.56 L m−2 h−1. Last but not least, the sponge can be driven and recycled magnetically. In conclusion, this promising multifunctional sponge can be applied as a new absorbent for oil-water separation.

Polydimethylsiloxane‐functionalized polyacrylonitrile nanofibrous aerogels for efficient oil absorption and oil/water separation

AbstractThe effective removal of oils and organic solvents from water is of great importance for environmental protection. Three‐dimensional nanofibrous aerogels (NFAs) with superabsorbent properties promise a huge potential applicability in oil spills and chemical leaks. However, the production of such NFAs through a facile and economical method is still a great challenge. Here, a very simple solution immersion process is presented to fabricate polydimethylsiloxane‐functionalized polyacrylonitrile NFAs. The obtained NFAs exhibit a superior chemical stability, a high hydrophobicity and an excellent absorption capacity for various oils and organic solvents. More importantly, these NFAs show an outstanding reversible elasticity and could potentially be employed for continuously collecting oils and organic pollutants from water with the assistance of a pump. It is believed that the obtained absorbents could be promising candidate materials for oil and organic solvent spill cleanups under harsh conditions.

Natural deep eutectic solvent (NADES): A strategy to improve the bioavailability of blueberry phenolic compounds in a ready-to-use extract

This study investigated whether a ready-to-use extract obtained using a natural deep eutectic solvent (NADES) affects the pharmacokinetic profile of blueberry phenolic compounds compared to organic solvent (SORG)-extracted compounds. SORG extract was administered as an aqueous solution after solvent removal. Wistar rats received a single dose of crude extract of blueberry obtained using NADES (CE-NADES) or SORG (CE-SORG), followed by LC-DAD-MS/MS analysis of blood and cecal feces. Non-compartmental pharmacokinetic analysis revealed that CE-NADES increased the bioavailability of anthocyanins by 140% compared to CE-SORG. CE-NADES increased the stability of phenolic compounds during in vitro digestion by delaying gastric chyme neutralization. These results suggest that besides being an eco-friendly solvent for the extraction of phytochemicals, choline chloride:glycerol:citric acid-based NADES can be used as a ready-to-use vehicle for increasing oral absorption of bioactive compounds such as anthocyanins.

Inherent Ethyl Acetate Selectivity in a Trianglimine Molecular Solid

Ethyl acetate is an important chemical raw material and solvent. It is also a key volatile organic compound in the brewing industry and a marker for lung cancer. Materials that are highly selective toward ethyl acetate are needed for its separation and detection. Here, we report a trianglimine macrocycle (TAMC) that selectively adsorbs ethyl acetate by forming a solvate. Crystal structure prediction showed this to be the lowest energy solvate structure available. This solvate leaves a metastable, “templated” cavity after solvent removal. Adsorption and breakthrough experiments confirmed that TAMC has adequate adsorption kinetics to separate ethyl acetate from azeotropic mixtures with ethanol, which is a challenging and energy‐intensive industrial separation.

One-pot synthesis of 1,2,4-oxadiazoles from chalcogen amino acid derivatives under microwave irradiation

A series of sulfur- and selenium-bearing, amino acid-derived 1,2,4-oxadiazoles were obtained by a simple procedure. The method consists of EDC-promoted coupling of chalcogen amino acid derivatives with arylamidoximes in acetone, followed by solvent removal and microwave irradiation in water medium. Influence of amidoxime substituents, of the chalcogen atom and of the amino acid side chain is discussed. The results showed this to be a fast, easy and effective method to obtain these compounds, with good functional-group tolerance, potentially favouring future applications in organic synthesis.

Three-Dimensional Reticulated, Spongelike, Resilient Aerogels Assembled by SiC/Si3N4 Nanowires.

For nanofibrous aerogels, a three-dimensional porous structure with interwoven nanofibers as a pore wall has become an urgent demand, and it remains to be a challenge to ensure the mechanical stability and thermal insulation. Other than the reported nanofiber as raw materials to generate three-dimensional cellular nanofibrous aerogels, an alternative low-cost and facile procedure has been proposed here via tactfully utilizing polymer sponge as a template attached with reactive particles, followed by a carbothermal reduction process to realize nanowire growth and their replacement of the original framework. The resulting spongy aerogels with numerous interlaced SiC/Si3N4 nanowires as a skeleton exhibit an ultrahigh porosity of 99.79%. Meanwhile, compressive elasticity after a compression at strain of 35% for 400 cycles, a low thermal conductivity of 23.19 mW/(m K), an excellent absorption capacity of 33.9-95.3 times for varied organic solvents removal, along with flexibility in shape design favored by the initial organic sponge make this nanofibrous aerogel an ideal material for heat shielding, absorption, or catalyst support.

Agarose, Alginate and Chitosan Nanostructured Aerogels for Pharmaceutical Applications: A Short Review.

In this short review, drug delivery systems, formed by polysaccharide-based (i.e., agarose, alginate, and chitosan) aerogels, are analyzed. In particular, the main papers, published in the period 2011–2020 in this research field, have been investigated and critically discussed, in order to highlight strengths and weaknesses of the traditional production techniques (e.g., freeze-drying and air evaporation) of bio-aerogels with respect to supercritical CO2 assisted drying. Supercritical CO2 assisted drying demonstrated to be a promising technique to produce nanostructured bio-aerogels that maintain the starting gel volume and shape, when the solvent removal occurs at negligible surface tension. This characteristic, coupled with the possibility of removing also cross-linking agent residues from the aerogels, makes these advanced devices safe and suitable as carriers for controlled drug delivery applications.

Silybum marianum glycerol extraction for the preparation of high-value anti-ageing extracts

Silybum marianum fruit is rich in silymarin, a flavonolignan mixture with hepatoprotective properties, whose favourable effects on skin make it a valuable ingredient in cosmetic products. The scope of the present study is to compare the efficiency of classic ethanol/water maceration with the maceration using mixtures of water with glycerol, a non-toxic, biodegradable, and affordable solvent, available from renewable sources. Furthermore, a glycerol-based ultrasound-assisted extraction (UAE) method was developed and optimized for silymarin content and antiradical activity. The prepared extracts were tested for their antioxidant and cosmeceutical activity. Maceration with glycerol/water mixtures was somewhat less efficient than the ethanol/water maceration. However, the extraction efficiency was significantly improved by means of ultrasonication. When UAE was conducted with 40 % (w/w) glycerol during 60 min at 80 °C the amount of extracted silymarin in the extracts was similar to that in the ethanol/water macerates (107.19 μg/mL vs. 116.17 μg/mL, respectively). Antiradical activity of the extracts was related to the silymarin content. The prepared extracts displayed mild Fe2+ chelating activity and hindered heat-induced degradation of polyunsaturated fatty acids, as well as elastase activity. Glycerol showed additive effects on the anti-tyrosinase activity of the extracts and was responsible for anti-inflammatory activity in the heat-induced coagulation assay. The presence of zinc, magnesium and other minerals with beneficial skin-related properties in S. marianum fruit further substantiate its use in cosmetics. The results indicate that glycerol extraction of S. marianum eliminates the need and energy necessary for solvent removal and enhances the desired functional and anti-ageing properties of the prepared extracts.

SOLVENT-FREE SYNTHESIS OF AMIDE: A NOVEL TECHNIQUE OF GREEN CHEMISTRY

Objective: Amide is one of the most important functional group presents in the chemicals, pharmaceuticals, and foods. Conventionally, it has been synthesized from the carboxylic acid and amines. This conventional reaction is lengthy and involves hazardous chemicals and solvents. Hence, it poses waste management, solvent removal, and environmental issues to the industries. To overcome this limitation, we have reported the green chemistry-based method for the synthesis of amide from carboxylic acid and urea.
 Methods: In this reaction, we have used boric acid as a catalyst, it is a simple and readily available compound. It is simple, efficient, and solvent-free procedure which involves the trituration of the reactant mixture and subsequent, direct heating of the triturated mixture.
 Results: The rate of reaction is very high and can synthesize the amide quickly.
 Conclusion: Various amides were prepared in good yield by this technique.

Morphological Stability of Organic Photovoltaics: Coarse‐grained Molecular Dynamics Simulation Studies

We have performed coarse‐grained molecular dynamics simulations of organic photovoltaic (OPV) 5wcells consisting of poly(3‐hexyl‐thiophene) (P3HT), phenyl‐C61‐butyric acid methyl ester (PC61BM), and phenyl‐C71‐butyricacid methyl ester (PC71BM) to investigate the effects of the solvent evaporation rate and the number of components in the morphological stability of OPV. Two different solvent evaporation processes were employed in this study. In the instantaneous solvent removal process, unstable pores are formed because of the slow translational relaxation of the electron receptors. In case of the gradual solvent removal process, the stable film formation is observed without any pore. In addition, the ternary OPV system shows better stability than binary systems by slowing down the phase separation.

딥코팅 공정을 이용하여 제작된 유연 인조혈관의 균일도 향상에 관한 연구

Three-dimensional (3-D) printing, with its capability for producing arbitrary shapes, has shown great potential for usage in patient-specific tissue engineering. However, if artificial tissues are fabricated directly through typical 3-D printing processes, the mechanical properties, particularly for softness or flexibility, significantly differ from those of natural tissues, resulting in inappropriate side effects during surgeries using vascular grafts. However, this can be overcome through the indirect 3-D printing of templates created with a thin-film formation process, such as dip coating. Dip coating is performed in two steps, including dipping/withdrawing a target base template from a polymer solution, and then drying the solvent into a solid thin film on the template. However, it is difficult to form a uniform layer on the arbitrary template because the gravitational flow of the coated solution disturbs the uniformity of the template as the solvent is drying. Therefore, we minimized the flow around the template after dip coating by rapidly removing the solvent removal by dipping the solution-coated template into ethanol. This reduced the solvent removal time and increased the viscosity of the coated solution, thereby alleviating the gravitational flow of the coated solution, and allowing us to successfully fabricate flexible vascular grafts.

Prospect of microcapsules as a delivery system in food technology: A review

Microencapsulation is the process by which any active substances are coated with the help of very small capsules. The size of the capsules can range from one micron to several hundred micron values. The usage of these capsules is not limited to any field; it plays important role in many industries related to pharmaceutical, biotechnology, food industries and in research applications as well. With the help of this latest technology encapsulation of vitamins, minerals, phytochemicals, flavors, omega-3 fatty acids, micro-organisms, enzymes, oils, peptides, protein hydrolysate, antioxidants and polyphenols is possible and there are many factors that play a vital role in the efficiency of microcapsules such as the concentration of polymer, rate of solvent removal, solubility of polymer insolvent, etc. microencapsulation can be done in many ways such as; spray drying, extrusion, lyophilization, coacervation, spray cooling, fluidized bed coating, co-crystallization and inclusion complexation. The article is a review of microencapsulation technology and lays emphasis on various substances that can be encapsulated with the help of this technique and different types of microencapsulation.

Development and Optimization of Controlled Release Formulation and Process of Levetiracetam with Hot Melt Coating Technology

Conventional coating processes are based on aqueous or organic solvent system, resulting in the lengthy and tedious processes where use and removal of solvents consumes lots of energy and resources. Also, solvent disposal is a critical issue considering environmental hazard.Hot melt coating process avoids use of solvent and is short and energy-efficient process. Here, Hot-melt coating process (HMCP) is being developed to formulate lipid based oral controlled release formulation system to deliver highly water soluble Biopharmaceutical Classification System (BCS) class-I drug Levetiracetam. Pellets containing Active ingredient in the core portion were prepared by extrusion spheronization process with use of appropriate filler and binder. These core pellets were then coated using hot-melt coating technology with different levels of lipid and a hydrophilic component. Formulation and Process parameters were optimized to achieve targeted drug release profile and other target product profile with particular focus onHMCP. Quality by design (QbD) with DOE approach was used for designing and development of the formulation, by putting risk assessment Failure Mode and Effect analysis (FMEA, Fish-bone diagram), screening (by Plackett Burman), and optimization by Central Composite Design (CCC) studies. Appropriate ‘design space’ was proposed based on the optimization studies. The results demonstrated that the level of Low melting coating component and a hydrophilic component influenced the drug release rate from the formulation, and the rate of release could be optimized by varying the amount of these components in the formulation. Processing parameters like Temperature of the coating solution and atomization air, Atomization air pressure and Spray rate also affects the drug release rate and other parameters like coating efficiency and mean particle size. For optimized formulation, dissolution data model fitting was also carried out which adequately fits to Higuchi model suggesting that the drug release occurred predominantly by diffusion.

High-efficiency oil/water absorbent using hydrophobic silane-modified plant fiber sponges

Increasing environmental problems caused by the emission of crude oil, petroleum products, and toxic organic solvents have threatened ecosystems and human health. Renewable and eco-friendly natural materials are considered as the most promising absorbents for removing oils and organic solvents from water. In this work, a hydrophobic plant fiber sponge (PFS) is successfully prepared via a simple vapor treatment strategy with hexamethyldisilazane (HMDS) (defined as PFS@HMDS). The as-prepared PFS@HMDS with high porosity, high mechanical durability, and excellent hydrophobicity with a water contact angle of 145° exhibits high oil absorptive capacity (15–40 g/g) and selectivity. It also shows the excellent structural stability, durability, and high reusability in the repeated absorption/desorption cyclic testing. More importantly, it can achieve continuous oil/water separation with the assistance of a miniature diaphragm pump. Owing to these favorable advantages, the PFS@HMDS demonstrates its potential application in oil/water separation and organic solvents removal.

Solvent-Casted Films to Assist Polymer Selection for Amorphous Solid Dispersions During Preclinical Studies: In-vitro and In-vivo Exploration

The use of two solvent-casted film methods to select optimal polymer compositions for amorphous solid dispersions prepared to support preclinical pharmacokinetic and toxicology studies is described. Evaporation of solvent from cover slips by using nitrogen flow, and solvent removal from vials by using rotary evaporation were employed. The films prepared on cover slips were evaluated under the microscope to determine crystallinity. The methods were validated by scaling up corresponding SDDs, evaluating SDD's dissolution, and comparing those results to the dissolution of drug-polymer films. Subsequently, SDD suspensions were prepared and dosed orally to rats to determine pharmacokinetic parameters. This was done by using three compounds from our pipeline and evaluating multiple polymers. The dissolution of generated films showed good agreement with the dissolution of spray dried dispersions when the films were fully amorphous (Compound A and B). In contrast, there was disagreement between film and SDD dissolution when the films had crystallized (Compound C). The in vivo exposure results indicated that the polymer choice based on the film screening methods would have been accurate for drug-polymer films that were amorphous (Compound A and B). Two additional case studies (Compound D and E) are presented, showing good agreement between in vivo and in vitro results. This study established the ability of two film casting screening methods to predict the in vitro and in vivo performance of corresponding SDDs, provided that the films are fully amorphous.

Hexafluoroisopropyl Sulfamate: A Useful Reagent for the Synthesis of Sulfamates and Sulfamides.

Sulfamates and sulfamides are most often synthesized from alcohols and amines with sulfamoyl chloride, which is an unstable reagent. We have identified hexafluoroisopropyl sulfamate (HFIPS) as a bench-stable solid that reacts readily with a wide variety of alcohols, amines, phenols, and anilines under mild reaction conditions. The sole byproduct of the reaction is hexafluoroisopropanol (HFIP) and reaction products can often be isolated in high purity after an aqueous workup (optional) and removal of solvents by evaporation.

Impregnation of Activated Carbon in Polyurethane Foam for Enhanced Solvent and Oil Adsorption from Water

This study illustrates the modification of the Poly-Urethane Foam (PUF) prepared from the Tung Oil (TO) and later impregnating it with varying ratio (~ 1 to 5 w/w%) of Activated Carbon (AC) which enable this modified entity to act as an effective adsorbent for the solvent and oil removal from the water. After its modification, it was found that the PUF impregnated with 5 w/w% AC displayed an enhanced solvent and oil adsorption capacity. The reusability of the adsorbent was observed to decrease with increasing number of cycles. Furthermore, the adsorption conduct was calculated in a batch-type process and validated using equilibrium and kinetics study. Here, the surface-modified PUF sorbent was characterized employing Scanning Electron Microscopy (SEM) and Contact Angle (CA) wettability study. Our findings inferred that with increasing AC ratio in the foam, its pore size and CA increases thereby enhancing the adsorption capacity making this proposed study to be more expedient for sustainable environment safety.

Obtainment of the spray-dried extracts of Peperomia pellucida L. (H.B.K.) using different atomization temperatures: physicochemical characterization and technological development for pharmaceutical applications.

Spray-dried extracts are prepared as powders or granules after solvent removal, which can be obtained in the presence or absence of pharmaceutical adjuvants. This work aimed to optimize the process of obtaining dried extracts of Peperomia pellucida L. (HBK) by spray drying. The characterization of the extract was performed by thermal analysis, specific surface area, particle size and high performance liquid chromatography (HPLC); then, capsules were developed for antimicrobial treatment, evaluating four bench lots by the determination of the angle of repose and time of flow, scanning electron microscopy, porosity and physicochemical quality control. There were no significant differences between the extracts obtained by spray drying at atomization temperatures of 140°C, 160°C and 180°C, which was confirmed by thermal analysis. Specific surface area varied inversely with the mean particle size. Regarding the marker content by HPLC, no significant differences were found between the samples, although the flavonoid fraction was more stable at 160°C. Bench lots (I to IV) were developed using the diluents Flowlac®, Starch® 1500, microcrystalline cellulose 250 and Cellactose® 80. Based on the results, the bench lot I, containing Flowlac®, was selected. The results of physicochemical quality control demonstrated that the selected formulation meets the pre-established parameters, and proving to be economically viable.