Pharmaceutical process research and

Neal Anderson, one of the outstanding practitioners of pharmaceutical process research and development, has given us here the best text ever written on the... 

The terminology graphical rate equation derives from our attempt to relate rate behavior to the reaction s concentration dependences in plots constructed from in situ data. Reaction rate laws may be developed for complex organic reactions via detailed mechanistic studies, and indeed much of the research in our group has this aim in mind. In pharmaceutical process research and development, however, it is rare that detailed mechanistic understanding accompanies a new transformation early in the research timeline. Knowledge of the concentration dependences, or reaction driving forces, is required for efficient scale-up even in the absence of mechanistic information. We typically describe the reaction rate in terms of a simplified power law form, as shown in Equation 27.4 for the reaction of Scheme 27.1, even in cases where we do not have sufficient information to relate the kinetic orders to a mechanistic scheme. 

Design of Experiments in Pharmaceutical Process Research and Development... 

This chapter provides a brief overview of DOE. Discussion of the technique s advantages and limitations are provided. Nine examples of its use in pharmaceutical process research and development are included. 

For decades, statistics has been applied to problems related to quality control and process improvement in the manufacturing environn nt. The applicability of statistical methods in the chemical process research and development area has also been recognized for many years. Despite the advantages offered by a statistical treatment of the data, it has only been recently that the use of design of experiments (DOE) has started to become routine in early pharmaceutical process research and development. 

Tucker, J.L. (2006) Green Chemistry, a Pharmaceutical Perspective. Organic Process Research and Development, 10, 315-319. 

The application of thermodynamic models to the correlation and prediction of pharmaceutical solubility behaviour is an underutilized technique in today s process research and development environment. This is due to the relatively poor accuracy and limited predictive ability of the previous generation of models. Recent advances in computational chemistry and an increased focus on the life science sectors has led to the development of more appropriate models with significantly improved predictive capabilities. The NRTL-SAC and Local UNIFAC approaches will be discussed here with additional examples given in section 8. 

The design of crystallization processes for the manufacture of Active Pharmaceutical Ingredients is a significant technical challenge to Process Research and Development groups throughout the Pharmaceutical and related industries. It requires an understanding of both the thermodynamic and kinetic aspects of crystallization, to ensure that the physical properties of the product will consistently meet specification. Failure to address these issues may lead to production problems associated with crystal size, shape and solubility, and to dissolution and bioavailability effects in the formulated product. 

Repic O. Principles of Process Research and Chemical Development in the Pharmaceutical Industry, Wiley, Hoboken, NJ, 1998. 

Petousis, N. H. 2002. Anatomy of Process Research and Development. In Erom Bench to Pilot Plant Process Research in the Pharmaceutical Industry, M. Nafissi, J. A. Ragan and K. M. DeVries, eds. Washington, DC American Chemical Society. 

The sitagliptin project helped rewrite the way that small-molecule pharmaceuticals are developed at Merck Process Research and set the foundations to realizing new ways for different groups to work together as a team in pursuit of a common goal. Dr. Rich D. Tillyer led the Process Research Department during this time of transformation, and we are thankful for his vision and for his support of innovation as the best way to develop new pharmaceutical compounds. 

Haseley, P., Oetjen, G.W. Opportunities and limitations of control of freeze drying by thermodynamic data from the process. Freeze drying of pharmaceuticals and biologicals. Center for Pharmaceutical Processing Research in cooperation with Purdue University and the University of Connecticut, USA, Sept. 1998... 

Resolutions of racemic mixtures are by far the most frequent applications of biocatalysts in the pharmaceutical industry. Repic et al., of the process research and development group at Novartis, recently published work to develop a method for the resolution of racemic (3-amino acid esters, an important class of intermediates for the preparation of peptidomimetics [21]. The Novartis group used Chiro-CLEC -EC [22] in 2% aqueous toluene to selectively acylate several different 3-amino esters (Fig. 4). The authors were able to isolate the desired (S) isomer of the amino esters in >95% ee in a simple one-step reaction and described it as a method which could be amenable for large-scale preparation. 

Ramesh N. Patel, Process Research and Development, Bristol-Myers Squibb Company, Pharmaceutical Research Institute, P.O. Box 191, New Brunswick, NJ 08903 patelR BMS.com Elba Pinto da Silva Bon, Instituto de Quimica, Universidade Federal do Rio de Janeiro, CEP 21949-900, Rio de Janeiro, RJ, Brasil elbal996 iq.ufrj. br... 

The oil and gas, chemical, polymer, and pharmaceutical industries are striving to create new products, catalysts, recipes, and processes. At the same time, they are challenged to shorten the time-to-market, ensure process and plant safety, and achieve regulatory compliance. Worldwide, the industries spend an estimated 500 billion annually in product and process research and development, pilot plants, process engineering, detailed engineering, construction and startup, manufacturing operations, and plant maintenance. 

My goal with this book is to provide a comprehensive, step-by-step, hands-on approach to organic process research and development for the preparation of small molecules. It should be useful to those in the pharmaceutical, fine chemical, and agricultural chemical industries and to those academicians who wish an insight into process R D in these industries. I hope it will ease the transition for those who are entering industrial process R D labs fresh from academia. More experienced readers may find some useful tips and ideas. 

Green chemistry in process research and developments in the pharmaceutical industry 03YGK464. 

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