Chirality, drug products

As with the bulk drug substance, spedfications for both enantiopure and racemic chiral drug products should include both a stereochemically spedfic identity test and stereochemically selective assay method. The analytical method to be used should not be arbitrarily chosen to be the same as for the bulk drug but should be chosen on the basis of the composition, method of manufacture, and stability characteristics of the formulation. 

However, it can be easily anticipated that, in the long term, stereoselective synthesis will dominate the stage of chiral drug production. Indeed, it is the authors belief that stereoselective synthesis will provide a great opportunity for new and exciting chemistry in both the academic and the industrial worlds. 

Case study MBRs for chiral drug production... 

The quality of a drug substance is controlled by its specification. An internationally harmonized guideline on specifications and tests for chemical substances as active ingredients and in drug products makes reference to chiral compounds. This has recently been finalized and is discussed in Section 13.5.2. 

Fig. 13-2. Establishing procedures for chiral new drug substances and new medicinal products containing new chiral drug substances.

Determination of the drug substance is expected to be enantioselective, and this may be achieved by including a chiral assay in the specification or an achiral assay together with appropriate methods of controlling the enantiomeric impurity. For a drug product where racemization does not occur during manufacture or storage, an achiral assay may suffice. If racemization does happen, then a chiral assay should be used or an achiral method combined with a validated procedure to control the presence of the other enantiomer. 

A different approach to making chiral drugs is asymmetric synthesis. An optically inactive precursor is converted to the drug by a reaction that uses a special catalyst, usually an enzyme (Chapter 11). If all goes well, the product is a single enantiomer with the desired physiological effect In 2001, William S. Knowles, Ryogi Noyori, and K. Barry Sharpless won the Nobel Prize in chemistry for work in this area. 

Chemical reaction A process in which one or more substances, called reactants, are converted to product(s), 67. See also Reaction, nonmetals, 575q, 555-558 Chernobyl nuclear accident, 525-526 Chiral center Carbon atom bonded to four different groups, 600 Chiral drugs, 601 Chloride ores, 535-536 Chlorinated water, 556 Chlorine... 

The question that must be addressed is which molecular species should be quantified in a bioequivalency study of a product containing a chiral drug ... 

Of much recent interest to the pharmaceutical industry and the U.S. Food and Drug Administration (FDA) is the production and sale of chiral drugs . 

The development of chiral phosphorus ligands has made undoubtedly significant impact on the asymmetric hydrogenation. Transition metal catalysts with efficient chiral phosphorus ligands have enabled the synthesis of a variety of chiral products from prochiral olefins, ketones, and imines in a very efficient manner, and many practical hydrogenation processes have been exploited in industry for the synthesis of chiral drugs and fine chemicals. 

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