Solvent and Process Selection

Other solvent properties such as freezing and boiling points, toxicjiy, corrosiveness, and flammability can also be used to guide the preliminary solvent selection since this information is usually available Bom other literature data or vendors, In addition, eolveni reactivity or decomposition properties should ba considered, 

A simple experimanc in which a proposed solvent is mixed with the feed mixture can be used to guide solvent selection evan if the equilibrium phases are not analyzed to determine concentrations. If lahotmory facilities are available, batch shakeout rests are often the mosi attractive way lo screen solvents and quickly identity a fow suitable candidates for further study. 

It is useful in such experiments to define a primary aad secondary break time. The primary break time is that tima required to form a clearly defined interface between the two phases. The secondary break time is that period needed for the quiescent liquid-liquid mixture to achieve clarity in ench of ihe balk phases after rapid agitation. Generally, the secondary break time is significantly greater then the primary break lime. 

for example, 5 mL of each phase are placed in a sample vial and vigorously agitated for 10-20 s, then the primary break tima should he on the order of 1-2 min, although Treybel has suggested this time conid be as greet as 5-10 min. However, ii is usually more advantageous if the primary break tima is less then 1 min. 

Liquid-liquid systems in which tB is short and clear phases are immediately formed are not necessarily attractive since this result probably indicates that little Or no soluie transfer occurred. On the other hand, systems that disengaga more slowly and result in hazy phases are not necessarily hed because they often suggest that at least one species ties transferred. If the phase disengagement at room temperature is unacceptable, betch shekeout tests can be conducted using a wami heih. 

Liquid-liquid extraction (LLE) is a versatile unit operation which may be used for many applications. Some examples include the recovery of a solute from a raffinate phase, treatment of a wash stream for secondary solute recovery, and the decontamination of wastewaters. In many applications, the solvent selection is a design variable and this choice remains largely a matter of trial and error. Although predictive techniques are available, there is really no substitute for a strong experimental program in screening solvents. 

The problem of solvent selection is relatively complex and a thorough treatment requires considerable information. In addition to basic liquid-liquid equilibrium data, knowledge of the phase densities, viscosities, and the liquid-liquid interfacial tension is also important. Moreover, the economics of IXE systems are often dominated by the solvent regeneration costs. If, for example, solvent regeneration b to be accomplished by extractive or azeotropic distillation, then vapor-liquM equilibrinm data for the ternary system must also be available. Insofar as the most interesting LLE systems ate often ffiose whidi are least ideal, the generation of a physical property data base to complete cost analysis is usually a sigruficant problem. 

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Chemical Flowsheet Basic unit operation selection with flow rates, conversion factors, temperatures, pressures, solvents and catalyst selection Process synthesis route Laboratory and pilot scale trials Knowledge of existing processes... 

Solvent and Process Greenness Scoring and Selection Tools... 

Solvent and Process Creenness Scoring and Selection Tools 69 Table 3.6 Variables used to calculate final category scores in the GSK SSC. 

The low energy solvent deasphalting process selectively extracts the more paraffinic components from vacuum residua while rejecting the condensed ring aromatics. As expected, deasphalted oil yields vary as a function of solvent type and quantity, and feedstock properties (Chapter 7). 

Anderson [2] presents a wide range of topics on pharmaceutical process development, including a number of different problems related to process scale-up, such as solvent and reagent selection, purification, and limitations to various operations. He notes that most reactors used for scale-up operations are selected for flexibility in running many different processes, especially for pilot plants and multiproduct manufacturing plants. 

Contaminants may be of three general types particulates, highly polar (ionic) residues, and nonpolar (grease-Uke) residues. In many production environments, all three types are present and several solvents and cleaning processes may be required to remove them. Both the choice of solvent or cleaning solution and the cleaning process are critical, and several theoretical principles may be followed in their selection. Ultimately, cleaning is more an art than a science, and the procedure chosen should be experimentally verified in each case. Qualitative and quantitative tests can be performed to determine the efficiency of a selected solvent and process. 

Teflon AF can be designed to have some solubility in selected perfluorinated solvents but remains chemically resistant to all other solvents and process chemicals. The solubility is typically only 3—15% by weight, but this allows solution-cast extremely thin coatings in the submicron thickness range. 

These plastics can also be welded using vibration and ultrasonic thermal processes. Solvent welding is also possible with selected solvents and processing conditions. 

Drug substance properties should be carefully evaluated. These property will dictate the excipients, method, and process selection for ASD product. The properties to be considered are solubility in organic and aqueous solvents, miscibility with polymers, melting point, particle size, and thermal stability. These properties determine manufacturability, product performance, and long-term stability. For example, hot melt extrusion cannot be used for thermally labile drug molecules (Forster et al. 2001 Vasconcelos et al. 2007 Leuner and Dressman 2000). Qn the other hand, for spray drying process, drug solubility determines the selection of the solvent as well as inlet process temperature (Vasconcelos et al. 2007 Leuner and Dressman 2000). 

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