Pharmaceutical drug development

HPLC has played an important role for years in the drug discovery process in pharmaceutical laboratories. HPLC has proven a valuable asset in purifications of drug from de novo synthesis, from biological matrices, and from combinational synthesis. HPLC assay has moved from the discovery laboratory on through manufacturing, production, and metabolite monitoring. 

LC/MS especially has been incorporated into building corporate-wide computer databases for tracking compounds throughout the process of candidate evaluation, approval, regulation, manufacturing, and environmental fate. This has lead to use of standardized LC/MS methods that are not optimized for each individual candidate, but allow computerized searching and comparison of compounds and structures. 

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Pharmaceutical drug development of small molecules is initially based on the selection of candidate targets - mainly enzymes, receptors or circulating proteins that are currently targeted by 45, 28 and 11% of marketed compounds, respec-... 

Pharmaceutical Drug Development Events, the Chemist s Viewpoint... 

A simplified view of the pharmaceutical drug development events (not to the time scale) is given in Fig. 1. 

FIG. 1. Pharmaceutical drug development events, a simplified view. Preclinicah Medicinal chemistry, combinatorial chemistry, process research. Clinical. Process R D Manufacturing (operations). 

Safety pharmacology program for pharmaceuticals. Drug Development Research, 35 (3), 179—182. 

Kennedy S.P. and B.J. Bormann (2006). Effective partnering of academic and physician scientists with the pharmaceutical drug development industry. Experimental Biology and Medicine 231 1690-1694. 

Pharmaceutical drug development has traditionally been performed in sequential phases, preclinical as well as clinical Phases I to III, in order to answer the two basic questions - which compound should be selected for development, and how it should be dosed. This information-gathering process has recently been characterized as two successive learning-confirming cycles (Fig. 1.4) [8, 9]. The first cycle (traditional Phases I and Ha) comprises learning - in healthy subjects -what dose is tolerated and confirming that this dose has some measurable bene-... 

Three comments are appropriate here. First, consideration of the traditional clinical trial design that has been the focus of attention up until this chapter is extremely worthwhile and instructive It has facilitated the introduction of fundamental design, methodology, and statistical concepts, and it will be an influential player in pharmaceutical drug development for many years to come. Second, the simple observation that the adaptive design may seem different does not in itself make it less valid, less valuable, or less important. Third, statistical approaches that are suitable for adaptive designs are, as yet, less well developed than they are for other study designs. 

This chapter is in honor to Vladimir Piotrovsky, who devoted a big part of his career to the application and implementation of modeling and simulation tools in pharmaceutical drug development at Johnson Johnson Pharmaceutical Research Development and beyond. We all miss his guidance and support. 

Korte R, Vogel F, Weinbauer GF. Primate Models in Pharmaceutical Drug Development. Muenster Waxmann, 2002 1-188. 

Zuhlke U, Korte S, Niggermann B, Fuchs A, Muller W. The common marmoset (Callithrix jacchus) as a model in biotechnology. In Korte R, Vogel F, Weinbauer GF, eds. Primate Models in Pharmaceutical Drug Development. Muenster Waxmann, 2002 119-25. 

PHARMACEUTICAL DRUG DEVELOPMENT EVENTS THE CHEMIST S VIEWPOINT... 

A team is a small number of people with complementary skills who are committed to a common purpose, performance goals, and approach for which they hold themselves mutually accountable. Teams, however, are not necessarily the answer to all business endeavors, but the challenges of new pharmaceutical drug development lends itself very well to this organizational approach. 

Robinson S, Delongeas J-L, Donald E, et al. A European pharmaceutical company initiative challenging the regulatory requirement for acute toxicity studies in pharmaceutical drug development. Regul Toxicol Pharmacol. 2008 50(3) 345-352. 

Weinbauer GF.The nonhuman primate as a model in developmental and reproductive toxicology. In Primate Models in Pharmaceutical Drug Development, edited by Korte R, Vogel E, and Weinbauer GF, pp. 49-64. Munster, Germany Waxmann Press, 2002. 

Srbek, J., Klejdus, B., Dousa, M., Bfichac, J., Stasiak, R, Reitmajer, J., and Novakovd, L. 2014. Direct analysis in real time—High resolution mass spectrometry as a valuable tool for the pharmaceutical drug development, Talanta, 130 518-526. 

Polymorphism has received widespread general interest in pharmaceutical drug development because of its impact on the physicochemical properties of APIs and also because of their economic significance. It is considered mandatory to perform a thorough and exhaustive sohd-form screening of all possible polymorphs of a lead drug molecule at the preformulation stage. The purpose is to discover as many solid forms as possible and to identify the most suitable... 

The Role of Separation Science in Pharmaceutical Drug Development... 

THE ROLE OF SEPARATION SCIENCE IN PHARMACEUTICAL DRUG DEVELOPMENT... 

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