Residual solvents in various products

There are physical and chemical barriers that control solvent removal from solid-solvent systems. The most basic relation is given by the following equation  

Bodi the partial pressure and Henry s law eonstant depend on temperature, pressure, and solvent properties. This relationship does not eonsider interaetion between solute and solvent In the ease of polymers, the Flory-Huggins theory gives a simplified relationship for low eoneenlrations of solvent  

Vapor pressures of some solvents ean be found in the refereneed monograph.  

The weight fraetion of residual solvent at equilibrium can be calculated from the following equation, which accounts for polymer-solvent interaction  

The last equation does not give the real values of residual solvents beeause equilibrium is not attained in real drying processes and the prediction of different interactions by the interaction parameter is too simplistic. The real values are substantially higher and the real barriers of solvent removal more complex. These are diseussed below. 

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The second part of this handbook (Chapters 14-25) is devoted more to the industrial use of solvents. Formulating with solvents applied in a broad range of industrial areas such as biotechnology, dry cleaning, electronic industry, food industry, paints and coatings, petroleum refining industry, pharmaceutical industry, textile industry, to mention only a few, is extensively described in Chapter 14. Standard and special mefriods of solvent detection and solvent analysis as well as the problem of residual solvents in various products, particularly in pharmaceutical ones, are the topics of Chapters 15 and 16. 

Gas chromatography is commonly used to analyse mixtures for quantification. A wide variety of special detectors with adequate linear response ranges are available for quantification of various classes of compounds (cf. Table 4.14). Quantification by direct injection may be used to determine additives, residual monomers and solvents in product formulations, coated films, and solid materials [109]. On the other hand, reliable quantification by means of solid-injection PTV-GC, HS-GC and PyGC techniques is not always trivial. 

In summary, there are at least four ways in which residual moisture in the amorphous state can impact on chemical reactivity. First, as a direct interaction with the drug, for example, in various hydrolytic reactions. Second, water can influence reactivity as a by-product of the reaction, by inhibiting the rate of the forward reaction, for example, in various condensation reactions, such as the Maillard reaction. Third, water acting locally as a solvent or medium facilitating a reaction, without direct participation. Finally, by virtue of its high free volume and low Tg, water can act as a plasticiser, reducing viscosity and enhancing diffusivity [28]. 

The determination of diazinon in foods is important because this chemical is used as a pesticide on plant crops and, at least in some cases, in pesticide dips for the control of parasitic infestations in animals (Brown et al. 1987 Miyahara et al. 1992). Because animals are exposed to this compound, both via pesticide dips and by ingestion of crops to which diazinon has been applied, some methods have been reported for animal products. The majority of methods, however, deal with the determination of residues in plant products. Most of the analytical methods found that describe the extraction from, and determination of, diazinon residues in various crops (plant materials) were developed as part of multiresidue methods. They are based on homogenization of the sample with an organic solvent (polar or non-polar) the isolation of the residues from this initial extract and, usually, some additional cleanup prior to the analysis of the extract by GC. The most common non-MS modes of detection exploit the... 

A number of solvents that are used for the synthesis of the API or formulation of the drug product can be present in the drug product. The content of these solvents, which are commonly called organic volatile impurities (OVI), is generally determined by the OVI methods specified in the compendia. Their content is controlled by the guidelines offered by various bodies (see Chapter 2). Residual solvents can affect the stability of drug product (see Sections IV. D and E). 

After the run has been completed, the product should be subjected to thorough analyses purity, impurity levels, residual solvents, and other appropriate tests. The product may also be examined for suitable conversion to the next intermediate. Yield, product purity, and the amount of product in various streams (e.g., aqueous extracts, mother liquors, and washes) can be used to calculate the mass balance for the processing. Monitoring the mass balance is an excellent way to determine how well a process is understood A low mass balance may be due to the formation of an impurity that could decrease product yield if not controlled in subsequent runs. 

Gas antisolvent processes can be performed in a semicontinuous mode. In this case the solution and the antisolvent are continuously introduced in the system until the desired amount of the product is formed. The introduction of the solution is then stopped and the DG flux extracts the residual solvent from the system. The system is then depressurized to enable collection of the product. The solution is generally introduced through an atomization nozzle that favors the prompt expansion of the solution and the formation of small particles. Different process configurations have been utilized, i.e., co- and countercurrent introduction of the solution and antisolvent fluxes and various nozzles have been designed. The process is referred to by different acronyms such as ASES (aerosol solvent extraction system), SAS (supercritical antisolvent), SEDS (solution enhanced dispersion by supercritical fluids), PCA (precipitation with a compressed fluid antisolvent), GASR (gas antisolvent recrystallization), GASP (gas antisolvent precipitation). 

In the past century, there has been a tremendous growth in pharmaceutical analyses and the role the analytical group plays in the development of new products. The baton was passed from techniques such as gravimetry, titrimetry, spectroscopy after extraction, and thin-layer paper chromatography to HPLC, gas chromatography, and various autoanalyzers. Emphasis was on tests such as assay, content and blend uniformity, and determination of impurities and residual solvents. 

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