Pharmaceutical solvents used

Solvent Extraction. Extraction processes, used for separating one substance from another, are commonly employed in the pharmaceutical and food processing industries. Oilseed extraction is the most widely used extraction process on the basis of tons processed. Extraction-grade hexane is the solvent used to extract soybeans, cottonseed, com, peanuts, and other oilseeds to produce edible oils and meal used for animal feed supplements. Tight specifications require a narrow distillation range to minimize solvent losses as well as an extremely low benzene content. The specification also has a composition requirement, which is very unusual for a hydrocarbon, where the different components of the solvent must be present within certain ranges (see Exthaction). 

Use as Solvent. Toluene is more important as a solvent than either benzene or xylene. Solvent use accounts for ca 14% of the total U.S. toluene demand for chemicals. About two-thirds of the solvent use is in paints and coatings the remainder is in adhesives, inks, pharmaceuticals, and other formulated products utilizing a solvent carrier. Use of toluene as solvent in surface coatings has been declining, primarily because of various environmental and health regulations. It is being replaced by other solvents, such as esters and ketones, and by changing the product formulation to use either fully soHd systems or water-based emulsion systems. 

Monochlorobenzene. The largest use of monochlorobenzene in the United States is in the production of nitrochlorobenzenes, both ortho and para, which are separated and used as intermediates for mbber chemicals, antioxidants (qv), dye and pigment intermediates, agriculture products, and pharmaceuticals (Table 5). Since the mid-1980s, there have been substantial exports of both o-nitrochlorobenzene, estimated at 7.7 million kg to Europe and -nitrochlorobenzene, estimated at 9.5 million kg to the Far East. Solvent use of monochlorobenzene accounted for about 28% of the U.S. consumption. This appHcation involves solvents for herbicide production and the solvent for diphenylmethane diisocyanate manufacture and other chemical intermediates. 

Over the last 30 years, ethanol s role as a solvent has increased sharply, while its role as a chemical intermediate has declined. In 1990, 59% of the 890 X 10 L demand was used for solvents and the remaining 41% was used for chemical intermediates (283). In 1960, solvents accounted for only 24% of the demand. The 1990 solvent uses were toiletries and cosmetics, 33% coatings, inks, and proprietary blends, 29% detergents and household cleaners, 14% external pharmaceuticals, 7% insecticides and disinfectants, 7% and miscellaneous, 10%. Ethanol demand for solvent appHcations has been fairly stable in recent years, growing at an average aimual rate of 2%. VOC regulations could impact its solvent use, particularly in areas like California, where ethanol in aerosols like hair spray and deodorants have come under scmtiny. 

Bioprocess plants are an essential part of food, fine chemical and pharmaceutical industries. Use of microorganisms to transform biological materials for production of fermented foods, cheese and chemicals has its antiquity. Bioprocesses have been developed for an enoimous range of commercial products, as listed in Table 1.1. Most of the products originate from relatively cheap raw materials. Production of industrial alcohols and organic solvents is mostly originated from cheap feed stocks. The more expensive and special bioprocesses are in the production of antibiotics, monoclonal antibodies and vaccines. Industrial enzymes and living cells such as baker s yeast and brewer s yeast are also commercial products obtained from bioprocess plants. 

MIBK is a valuable industrial solvent used primarily in the paint and coating industry and in metallurgical extraction processes. It is also used as a precursor in the production of specialty chemicals such as pesticides, rubber anti-oxidants as well as antibiotics and pharmaceuticals (1). Historically, MIBK has been produced commercially from acetone and hydrogen feedstock in three stages. First, acetone is dimerized to produce diacetone alcohol (DAA). Second, DAA is dehydrated to produce MO and water. Finally, the carbon-carbon double bond of MO is selectively hydrogenated to produce MIBK. These consecutive reactions are outlined in equations (1-3). 

The habit of pharmaceutical compounds has been used for purposes of identification, although the method can only be reliably used when the crystallization solvent used to generate the test crystals is carefully controlled. Since the faces of a crystal must reflect the internal structure of the solid, the angles between any two faces of a crystal will remain the same even if the crystal growth is accelerated or retarded in one direction or another. Toxicologists have made extensive use of microscopy following multiple recrystallization, and they have developed useful methods for compound identification [5]. 

Mat r industries use phenolic materials in their manufacturing processes. Phenol is also used in the production of dmgs, weed killers, and synthetic resins. Phenol and its derivatives are present in the wastewaters of industries such as cooking, pulp mills, paint and dyes, wine distilleries, oil and gasoline, synthetic rabber, textiles, pharmaceuticals, solvent, manufacture of pesticides, paper, and wood etc. [1]. 

Titrations in non-aqueous solvents have been traditionally an important tool for the accurate determination of various pharmaceuticals, some acids in foods, use of some acids or bases in detergents, cosmetics and textile auxiharies, in the analysis of industrial process streams, the analysis of polymers [1-7]. The determination of the pK or pK values of organic compoimds with acidity or basicity constant less than 10 can only be reahsed in non-aqueous media. Although water has excellent solvent properties, it is not suitable for such organic compotmds since the pH jump at the equivalence point in aqueous solution carmot be evalrrated with reasonable accuracy, with this resrrlt, the end point carmot be found. Moreover, most of this compotmds ate not soluble in water. For these reasons, titration in non-aqueous media has recently acqttired great importance. It is now well known that non-aqueous titrations greatly depend on the solvents used [4, 8-13]. 

Baseline separation of the cephalosporin antibiotic cephradine, its main impurity cephalexin, and other related impurities was achieved by MEKC. The method was validated in compliance with the USP XXII analytical performance parameters and the results were comparable with a validated LC method, depicting CE to be a valuable alternative technique to LC in pharmaceutical quality control. In most cases, the amount of impurities relative to the main compound measured by MEKC is similar to that obtained by LC. However, some reports reveal that there are differences in number and amount of impurities between MEKC and LC analysis. MEKC permitted the determination of seven known and three unknown impurities in cefotaxime and the results were in good agreement with those of LC. ° MEKC yielded a higher amount of the cefotaxime dimer but a lower amount of an unidentified impurity with respect to LC. The differences may be due to the easier formation of the dimer in the aqueous sample solvent used in MEKC compared to the hydroorganic... 

Uses Intermediate in the manufacture of dyes, resins, varnishes, medicinals, perfumes, photographic chemicals, shoe blacks, chemical intermediates, pharmaceuticals solvent vulcanizing rubber isocyanates for urethane foams explosives petroleum refining diphenylamine phenolics fungicides herbicides. 

Microwave-assisted synthesis is attractive to researchers for many reasons, including speed, yields, and the potential for reduced solvent use. Raman monitoring offers a convenient way to elucidate the chemical mechanism while instantly, continuously monitoring reaction kinetics. This enables rapid, data-driven process optimizations without concerns about safely and accurately sampling out of a microwave vessel stopped mid-reaction. Pivonka and Empheld of AstraZeneca Pharmaceuticals describe the continuous acquisition of Raman spectra of an amine or Knoevenagel coupling reaction in a sealed microwave reaction vessel at elevated temperatures and pressures [134]. 

Common solvent in the chemical and pharmaceutical industries used in the production of lubricating oils and as intermediary in the manufacture of chloroform and in the manufacture of plastics, paints, varnishes and cosmetics. 

Impurities, in contrast to degradation products, might or might not have any relation to the drug molecule. In the simplest case, residual quantities of a solvent used at some step in the process chemistry can become an impurity in the drug product. A recent, very extensive publication to which the interested reader is referred, listed the proton and carbon NMR chemical shifts of a large number of potential solvent impurities in a number of commonly employed NMR solvents [22]. There have also been several reviews on the topic of residual solvents in pharmaceuticals [23, 24]. 

Ester synthesis of cholesterol linoleate. Cholesterol fatty acid ester is an important cell membrane lipids and has many applications in cosmetics, pharmaceutical and other industries. Akehoshi et aL(7) reported the ester synthesis of the cholesterol fatty acid ester with native lipase. Synthesis of the cholesterol fatty acid ester was also carried out in water-saturated n-hexane by palmitic acid-modified lipase. As shown in Table III, this system made it possible for the synthesis of the cholesterol fatty acid ester in organic solvents using the modified lipase. 

Another important issue in green chemistry is the use of organic solvents. The use of many traditional organic solvents, such as chlorinated hydrocarbons, has been severely curtailed. Indeed, so many of the solvents that are favored by organic chemists have been blackhsted that the whole question of solvent use requires rethinking and has become a primary focus, especially in the manufacture of pharmaceuticals [29, 30]. In our original studies of E factors of various processes. 

Figure 3.1 identifies the major stages in a solvents life cycle production, transport, use, and disposal. Although there are many opportunities to recycle and reuse solvents they will eventually need to be disposed of as waste. As an example, consider a process which uses tetrahydrofuran (THF). A 1 kg reduction in the amount ofTHF would reduce the CO2 emissions from THF production by about 16kg [3], This reduction in CO2 emissions does not account for the savings in transportation or disposal of excess THF in a process. Therefore, reductions in solvent use by the pharmaceutical industry not only reduce the waste it produces as part of its processes but also the waste that would be generated from the manufacture of additional solvent. 

Along with methods to evaluate different pharmaceutical processes and unit operations, several methods have also been developed to evaluate commonly used solvents in the pharmaceutical industry. Solvents still account for a majority of the mass utilization in any pharmaceutical process. Therefore, various methods have been developed which focus on measuring the greenness of solvents, locating possible alternatives and reducing the overall amount of solvent used in any given process. Some of these methods use a combination of physical property data, LCA... 

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