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Manufacturing Techniques for Nanoparticles in Drug Delivery
Published in Yasser Shahzad, Syed A.A. Rizvi, Abid Mehmood Yousaf, Talib Hussain, Drug Delivery Using Nanomaterials, 2022
Daniel Real, María Lina Formica, Matías L. Picchio, Alejandro J. Paredes
The salting-out technique consists of separating a water-miscible solvent from aqueous solution via the salting-out effect (Galindo-Rodriguez et al., 2004). The solvent used to prepare a polymer and drug solution should be totally miscible with water (usually acetone). Emulsification is conducted with an aqueous phase containing a high concentration of salting-out agents (electrolytes, such as calcium chloride, magnesium acetate, magnesium chloride, or nonelectrolytes like sucrose) and a colloidal stabilizer. The saturated aqueous phase prevents the solvent from mixing with water. The emulsified droplets are then diluted in water. A sudden drop of salt concentration in the continuous phase causes the extraction of organic solvent and precipitation of polymer-drug NPs, as illustrated in Figure 2.8. Afterwards, both the salting-out agents and the solvent should be eliminated by cross-flow filtration. The main drawbacks are the extensive washing steps and the limited application to lipophilic drugs (Mendoza-Munoz et al., 2012). The principal advantages of salting-out are the minimum stress produced in proteins and heat-sensitive substances encapsulation.
Introduction and Basics of Nanotechnology
Published in Rakesh K. Sindhu, Mansi Chitkara, Inderjeet Singh Sandhu, Nanotechnology, 2021
Anjali Saharan, Pooja Mittal, Kashish Wilson, Inderjeet Verma
The salting out method is used for the separation of the water-miscible solvent from aqueous solution using the salting out effect. It is based on the separation of a water-miscible solvent from the aqueous solution via the salting out effect. Further, the polymer and the drug are initially dissolved in a solvent, which is subsequently emulsified into an aqueous gel containing the salting out agent, such as electrolytes magnesium chloride and calcium chloride, or non-electrolytes such as sucrose, and a colloidal stabilizer such as polyvinyl pyrrolidone or hydroxyethyl cellulose. This oil/water emulsion is diluted with a sufficient volume of water or aqueous solution to enhance the diffusion of solvent into the aqueous phase, which helps in the formation of nanospheres. Various manufacturing parameters can be varied, including stirring rate, internal/external phase ratio, concentration of polymers in the organic phase, type of electrolyte concentration, and type of stabilizer in the aqueous phase. Polymers drafted using this method, such as poly(methacrylic) acids and ethyl cellulose nanospheres, have very high efficiency. A major advantage of this method is that it does not require heat for manufacturing and can be highly effective for manufacturing thermolabile products easily. The major flaws in this method are application of lyophilic drugs and extensive steps of washing nanoparticles.
Liquid-Liquid Separation
Published in Pau Loke Show, Chien Wei Ooi, Tau Chuan Ling, Bioprocess Engineering, 2019
Hui Yi Leong, Pau Loke Show, K. Vogisha Kunjunee, Qi Wye Neoh, Payal Sunil Thadani
Next, typical types of salts used in experiments are potassium dihydrogen phosphate (KH2PO4), dipotassium hydrogen phosphate (K2HPO4), magnesium sulphate (MgSO4), and ammonium sulphate ((NH4)2SO4). For protein extraction situations, salts with lower molecular weight have a greater tendency to separate with increasing partition coefficient. Salts that show salting out effect have better biphasic system formation and separation efficiency, and this can be achieved by manipulating the concentration of salt. Overall, there is no certain alcohol/salt combination because each biomolecule possesses individual traits and properties. Thus, it is recommended to conduct several tests to select the appropriate solvent before executing any experiments.
A Survey of Extraction Chromatographic f-Element Separations Developed by E. P. Horwitz
Published in Solvent Extraction and Ion Exchange, 2020
Erin R. Bertelsen, Jessica A. Jackson, Jenifer C. Shafer
Previous solvent extraction work by Horwitz using Aliquat-336 in xylene had shown large separation factors between Am(III) and Cm(III) by salting-out with lithium, magnesium, or aluminum nitrate.[8,45] The phenomenon known as “salting-out” is largely due to the effective decrease in the aqueous phase water concentration as the electrolyte concentration within the aqueous phase increases, thus causing the cation of interest to be less solvated by water molecules.[27] This, in turn, makes the cation less hydrophilic and easier to extract.
Measurement and thermodynamic modeling of ternary (liquid + liquid) equilibria for extraction of 2,3-butanediol from aqueous solution with different solvents at T = 298.2 K, T = 308.2 K, and T = 318.2 K
Published in Chemical Engineering Communications, 2022
Yanyang Wu, Weipeng Chen, Renlong Li, Bin Wu, Lijun Ji, Kui Chen
2,3-Butanediol (2,3-BD) is a promising fuel because of its high antiknock index and heating value (Haider Harvianto, et al. 2018; Harvey et al. 2016). Besides, 2,3-BD can be used as an important intermediate chemical for the synthesis of polymers, which was widely applied in the food, cosmetics, and plastics industries (Celińska and Grajek 2009; Ji et al. 2011; Song et al. 2019). Microbial production of 2,3-BD was first reported in 1906 (Harden 1906). Since then, 2,3-BD has gained wide-spread interest as a biomass-derived organic chemical that can replace fossil fuels and fossil-based chemical feedstocks (Parate et al. 2018; Shrivastav et al. 2013; Song et al. 2018). However, there are intrinsic barriers which restrict the industrial bio-production of 2,3-BD: separation from the fermentation broth, due to the strong hydrophilicity and low volatility, and the complexity of its corresponding fermentation broth (containing ∼15% 2,3-BD). Although many experimental studies were done at the laboratory scale, each of them has certain limitations for its applicability to the commercial-scale production of 2,3-BD. In the process of pervaporation, the selectivity of the membrane is low due to the hydrophilic nature of 2,3-BD, and membrane swelling is also an issue (Dettwiler et al. 1993; Hong et al. 2019; Shao and Kumar 2009, 2011). In terms of reactive extraction (Li et al. 2012, 2016, 2013a, 2013b), it faces the recovery issue of catalyst. Furthermore, anti-corrosive devices are required for the strongly acidic catalyst (Koutinas et al. 2016). The salting-out method enhances the separation factor and reduces the solvent amount (Birajdar et al. 2015a, 2015b; Dai et al. 2011, 2014, 2017, 2018). However, the salt will adversely influence the recovery of the solvent in the distillation process (Xie et al. 2017). In contrast, liquid–liquid extraction seems to be more promising for the separation of 2,3-BD in aqueous solution (Kislik 2012).
From second generation feed-stocks to innovative fermentation and downstream techniques for succinic acid production
Published in Critical Reviews in Environmental Science and Technology, 2020
Enrico Mancini, Seyed Soheil Mansouri, Krist V. Gernaey, Jianquan Luo, Manuel Pinelo
Salting out is a potential SA separation method which simultaneously removes cells and proteins from the fermentation broth and thus centrifugation and filtration steps can be omitted (Sun, Yan, Fu, & Xiu, 2014). The process is based on the interaction between electrolyte and nonelectrolyte compounds, where (the nonelectrolyte) would become less soluble under high salt concentration conditions and as a consequence precipitates out. The method allows the extraction of hydrophilic compounds, such as some organic solvents, from an aqueous solution. For example, Sun et al. (2014) investigated SA separation from a real (glucose-based fed-batch fermentation) and a synthetic fermentation broth by means of salting out and subsequent crystallization. The salting out mechanism for SA separation is governed by factors such as salt and solvent concentrations and SA dissociation form. In their study, Sun et al. (2014) first lowered the fermentation broth pH (from A. succinogenes on spent sulfite liquor feedstock) to 3.0 with H2SO4, then added acetone (30%) and (NH4)2SO4 (20%) to induce SA partitioning. The SA-acetone phase was purified with activated carbon which was then removed by filtration under vacuum evaporation to enable acetone recovery. Subsequently, crystallization was carried out at pH 2.0 and 4 °C for 24 h. Finally, SA crystals were washed and dried at 70 °C for 12 h. SA yield and purity were 65% and 97%, respectively, from the synthetic fermentation broth, whereas the values for yield and purity were 65% and 91%, respectively, from the actual fermentation broth, and 99.03% of the cells and 90.82% of the proteins were removed by direct salting out (without any preceding filtration steps). The same process was investigated by Alexandri et al. (2019) in their comparative separation and purification study (previously mentioned) which achieved 50% and 86% yield and purity, respectively. Even though extraction can lead to high SA purity through simultaneously separating cells and proteins from the fermentation broth and thus replacing for centrifugation and/or filtration steps, the yield is limited. Furthermore, if xylose is present in the fermentation broth, it will crystalize with SA and lower the final product purity. Therefore, since lignocellulosic material (which is rich in xylose) has been identified as the future most important feedstock for SA production, a combination of salting out and crystallization for product recovery would potentially not be a successful strategy to separate and purify the SA if the fermentation process is not highly controlled to avoid the presence of residual xylose.