Pharmaceuticals industrial processing

Riekkola, M. L., and Wiedmer, S. K. (1997). Potential of capillary electrophoresis with micelles or chiral additives as a purity control method in pharmaceutical industry. Process Control Qual. 10, 169-180. 

Table 2.2 Comparison between chemical and pharmaceutical industry processes with respect to process analytics...

According to Coimbra et solvents play a central role in the majority of chemical and pharmaceutical industrial processes. The most used method to obtain artemisinin (1) from A. annua is through the use of organic solvents such as toluene, hexane, cyclohexane, ethanol, chloroform and petroleum ether. Rodrigues et al described a low-cost and industrial scaled procedure that enables artemisinin (1) enhanced yields by using inexpensive and easy steps. Serial extraction techniques allowed a reduction of 65% in solvent consumption. Moreover, the use of ethanol for compound extraction is safer when compared to other solvents. Flash column pre-purification employing silicon dioxide (Zeosil ) as stationary phase provided an enriched artemisinin (1) fraction that precipitated in hexane/ethyl acetate (85/15, v/v) solution. These results indicate the feasibility of producing artemisinin (1) at final cost lowered by almost threefold when compared to classical procedures. 

As more restrictions on product preservatives have been set in the last 10 years, more instances of microbial contamination have appeared and liquid detergent process equipment and operations have approached those used in the food and pharmaceutical industries. Process equipment is being installed to a more sanitary level, which means easier to clean and disinfect. Predominantly the equipment is designed for cleaning in place (CIP) without the need to disassemble. This chiefly means that surfaces are polished, circulation dead spaces are avoided, and drainage is virtually perfect. Usually the equipment is washed with alkaline and acid solutions, and then with a disinfectant solution. Additional equipment to handle and recirculate disinfectant solutions becomes part of the system design. 

In the pharmaceutical industry, process tanks, pipes, and valves are often electro-polished to reduce adhesion of products and decrease bacterial growth in crevices. It is also necessary to prevent contamination of packages by spilled products, and hence desiccant bags filled with drying agents are placed in packages. The atmosphere in the packages is controlled humidity to avoid corrosion. 

The electrical response of MWCNTs/I FPMPc was evaluated in air-tight chamber at room temperature. The NH3-sensing properties of the developed sensor demonstrated high stability and reproducibility, fast response/recovery, and noticeable selectivity for NH3, as can be observed in Fig. 8b. Such achievements make this type of device potentially useful in applications such as environmental monitoring and chemical/pharmaceutical industrial processing. 

The chiral Mn-salen catalysts have successfully been used in pharmaceutical industry processes. For example, enantioselective epoxidation of indene 43 under Jacobsen et al. s conditions provided epoxide 44 in 71% yield and 84—86% ee. It was reported that both yield and enantiose-lectivity were increased by adding 4-phenylpyridine N-oxide (PPNO) as co-oxidant in the system. A modified Ritter reaction converted indene oxide 44 into the c -amino alcohol 46. The enantiomeric purity of 46 was enhanced to >99% ee by formation of the corresponding L-tartrate salt followed by recrystallization. Amino alcohol 46 was identified as a critical component of the highly effective HIV protease inhibitor Indinavir 47 developed by Merck (White-house Station, NJ) (Scheme 35.12). ... 

Pharmaceutical Processes. The pharmaceutical industry is a principal user of extraction because many pharmaceutical intermediates and products ate heat-sensitive and cannot be processed by methods such as distillation. A usehil broad review can be found in the Hterature (241). 

The combined pharmaceutical appHcations account for an estimated 25% of DMF consumption. In the pharmaceutical industry, DMF is used in many processes as a reaction and crystallizing solvent because of its remarkable solvent properties. For example, hydrocortisone acetate [50-03-3] dihydrostreptomycin sulfate [5490-27-7] and amphotericin A [1405-32-9] are pharmaceutical products whose crystallization is faciHtated by the use of DMF. Itis also a good solvent for the fungicide griseofulvin/72%(97-< 7 and is used in its production. 

Full details of this work were pubHshed (6) and the processes, or variants of them, were introduced in a number of other countries. In the United States, the pharmaceutical industry continued to provide manufacturing sites, treating plasma fractionation as a normal commercial activity. In many other countries processing was undertaken by the Red Cross or blood transfusion services that emerged following Wodd War II. In these organisations plasma fractionation was part of a larger operation to provide whole blood, blood components, and speciaUst medical services on a national basis. These different approaches resulted in the development of two distinct sectors in the plasma fractionation industry ie, a commercial or for-profit sector based on paid donors and a noncommercial or not-for-profit sector based on unpaid donors. 

Nitromethane. The nitroparaffins are used widely as raw materials for synthesis. Nitromethane is used to produce the nitro alcohol (qv) 2-(hydroxymethyl)-2-nitro-l,3-propanediol, which is a registered biocide useful for control of bacteria in a number of industrial processes. This nitro alcohol also serves as the raw material for the production of the alkanolamine (qv) 2-amino-2-(hydroxymethyl)-l,3-propanediol, which is an important buffering agent useful in a number of pharmaceutical appHcations. 

RO is also used to produce ultrapure water for many laboratory uses (90) as weU as in the medical and pharmaceutical industries (91). As for the electronics industry, purity is achieved using a combination of processes. A typical hybrid process for the production of ultrapure water is shown in Figure 11. The order in which the various steps take place may vary from case to case. 

Uses. The main use of dextrose is in food processing (qv), where it is of value for its physical, chemical, and nutritive properties. Dextrose is also used in nonfood appHcations in the chemical, dmg, and pharmaceutical industries. This latter segment of the market represents about 21% of dextrose... 

In the early years of the chemical industry, use of biological agents centered on fermentation (qv) techniques for the production of food products, eg, vinegar (qv), cheeses (see Milk and milk products), beer (qv), and of simple organic compounds such as acetone (qv), ethanol (qv), and the butyl alcohols (qv). By the middle of the twentieth century, most simple organic chemicals were produced synthetically. Fermentation was used for food products and for more complex substances such as pharmaceuticals (qv) (see also Antibiotics). Moreover, supports were developed to immobilize enzymes for use in industrial processes such as the hydrolysis of starch (qv) (see Enzyme applications). 

Sodium Tetrahydroborate, Na[BH ]. This air-stable white powder, commonly referred to as sodium borohydride, is the most widely commercialized boron hydride material. It is used in a variety of industrial processes including bleaching of paper pulp and clays, preparation and purification of organic chemicals and pharmaceuticals, textile dye reduction, recovery of valuable metals, wastewater treatment, and production of dithionite compounds. Sodium borohydride is produced in the United States by Morton International, Inc., the Alfa Division of Johnson Matthey, Inc., and Covan Limited, with Morton International supplying about 75% of market. More than six million pounds of this material suppHed as powder, pellets, and aqueous solution, were produced in 1990. 

Supercritical fluid extraction (SFE) has been widely used to the extraction processes in pharmaceutical industries. Besides application of SFE in phannaceuticals, it has been applied on a wide spectmm of natural products and food industries such as natural pesticides, antioxidants, vegetable oil, flavors, perfumes and etc [1-2]. 

The precious metals are many times the cost of the base metals and, therefore, are limited to specialized applications or to those in which process conditions are highly demanding (e.g., where conditions are too corrosive for base metals and temperatures too high for plastics where base metal contamination must be avoided, as in the food and pharmaceutical industries or where plastics cannot be used because of heat transfer requirements and for special applications such as bursting discs in pressure vessels). The physical and mechanical properties of precious metals and their alloys used in process plants are given in Table 3.38. 

The pharmaceutical industry has employed materials of plant and animal origin as sources of drugs. The industry has utilized the life processes of either plants or animals and microorganisms to produce medicinal and antibiotic products. 

The Kolbe-Schmitt reaction is limited to phenol, substituted phenols and certain heteroaromatics. The classical procedure is carried out by application of high pressure using carbon dioxide without solvent yields are often only moderate. In contrast to the minor importance on laboratory scale, the large scale process for the synthesis of salicylic acid is of great importance in the pharmaceutical industry. 

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