Pharmaceutical products process synthesis

Enantiometrically pure alcohols are important and valuable intermediates in the synthesis of pharmaceuticals and other fine chemicals. A variety of synthetic methods have been developed to obtain optically pure alcohols. Among these methods, a straightforward approach is the reduction of prochiral ketones to chiral alcohols. In this context, varieties of chiral metal complexes have been developed as catalysts in asymmetric ketone reductions [ 1-3]. However, in many cases, difficulties remain in the process operation, and in obtaining sufficient enantiomeric purity and productivity [2,3]. In addition, residual metal in the products originating from the metal catalyst presents another challenge because of the ever more stringent regulatory restrictions on the level of metals allowed in pharmaceutical products [4]. An alternative to the chemical asymmetric reduction processes is biocatalytic transformation, which offers... 

The synthesis of aldehydes via hydroformylation of alkenes is an important industrial process used to produce in the region of 6 million tonnes a year of aldehydes. These compounds are used as intermediates in the manufacture of plasticizers, soaps, detergents and pharmaceutical products [7], While the majority of aldehydes prepared from alkene hydroformylation are done so in organic solvents, some research in 1975 showed that rhodium complexes with sulfonated phosphine ligands immobilized in water were able to hydroformylate propene with virtually complete retention of rhodium in the aqueous phase [8], Since catalyst loss is a major problem in the production of bulk chemicals of this nature, the process was scaled up, culminating in the Ruhrchemie-Rhone-Poulenc process for hydroformylation of propene, initially on a 120000 tonne per year scale [9], The development of this biphasic process represents one of the major transitions since the discovery of the hydroformylation reaction. The key transitions in this field include [10] ... 

To gain FDA approval or license for marketing, a pharmaceutical product must be shown to be safe and effective for its proposed or intended use. The drug company or sponsor must also provide evidence to show that the processes and control procedures used for synthesis, manufacture, and packaging are independently validated to ensure that the pharmaceutical product meets established standards of quality. The overall effort from the inception of a new molecular entity and the establishment of analytical, scale-up, and quality control procedures, to the collection of safety and efficacy data for consideration by the FDA as part of an NDA or BLA, is called the drug development process. 

To invoke a cliche, pharmaceutical product development is an art form (Fig. 3) (2). Pharmaceutical products and processes are developed primarily by recipe-driven trial-and-error methods. Typically, the first stage (drug synthesis) yields a drug substance in powder form. In the second stage... 

Residual solvents are organic volatile chemicals that remain in active substances, excipients, and other pharmaceutical products after processing. In spite of their toxic properties, solvents play an important role in the production of pharmaceuticals, during the synthesis, separation, or purification, and their use cannot be avoided. Solvents in this category do not include those used as excipients. 

At least one of the 12 principles—number 2, design safe products—is a must for pharmaceutical synthesis. Indeed, pharmaceutical products are regulated and tested for safety. Principle number 7, maximize atom economy, refers to a metric against which the greenness of a process may be evaluated. Green metrics are covered in the next section. 

The purpose and object of this book are to establish a link between INN s3), structure, synthesis and production processes, patent (and literature) situation, medical use and trade names of important pharmaceuticals. 

The development of a novel production system for D-pantoyl lactone (which is a lactone compound carrying a chiral hydroxy group and a chiral intermediate for the commercial production of D-pantothenate) by microbial asymmetric reduction has been undertaken. D-pantothenate is mainly used in various pharmaceutical products and as an animal feed additive, the current world production of calcium pantothenate being about 6,000 tons per year. Conventional commercial production of D-pantoyl lactone has depended exclusively on chemical synthesis involving optical resolution of a chemically synthesized racemic pantoyl lactone, which is the most troublesome step of the pantothenate synthesis process. 

Pharmaceutical products can be readily classified and arranged by their therapeutic functions. Classification according to chemical criteria is more difficult, because the pharmaceutical industry employs more complicated steps in its manufacturing processes than most other chemical industries. In this section, we will briefly describe the various therapeutic classes of drugs and we will also include the reactions involved in the synthesis of some representative examples of drug substances. 

Chemical synthesis [16]. Synthetic active ingredients and other compounds used in the production of pharmaceutical products are prepared by chemical synthesis using a batch processing. A complex series of reactions... 

Aniline is the parent compound of the aromatic amines, which are used in the synthesis of agrochemicals, dyes, and pharmaceuticals. There is a concern that aromatic amines may be released into the environment during production processes or incomplete treatment of industrial waste streams. Additiondly, aromatic amines can enter the environment from the reduction of azo dyes, polynitroaromatic munitions (e.g. TNT), and dinitro herbicides, and from hydrolytic degradation of several classes of pesticides, including the phenylurea, phenylcarbamate, and acylanilide herbicides. 

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