Pharmaceutical Process Chemistry for Synthesis

There is a need to explain that generic versions of a drug may not be manufactured by the same process as brand-name drugs and that the different processes may have dramatically different environmental impacts. Two global forces are at odds today—the push for "greener" processes and the push for lower drug prices. This book brings this conflict into sharp focus by discussing in detail the published process chemistry for top-selling small molecule drugs.

Providing insights about process route selection, choice of reagents, and reaction conditions, Pharmaceutical Process Chemistry for Synthesis guides process chemists in identifying best processes for manufacturing these blockbuster drugs as they lose patent protection. Further, it highlights the strategies and methodology that might be useful for expediting the process research and development of the blockbusters of the future.

Written from a refreshingly objective perspective, this book is essential for process chemists who need to devise practical syntheses for increasingly complex drugs in a constantly decreasing time frame.

1 Introduction.

2 Actos® (Pioglitazone Hydrochloride).

3 Lexapro® (Escitalopram Oxalate).

4 Efferox XR® (Venlafaxine Hydrochloride).

5 Seroquel® (Quetiapine Hemifumarate).

6 Singulair® (Montelukast Sodium).

7 Prevacid® (Lansoprazole).

8 Advair Diskus® (Salmeterol Xinafoate).

9 Lipitor® (Aatorvastatin Calcium).

Index.

"This book presents detailed discussions of the published process chemistry of the ten top-selling small molecule drugs in the US in 2007, information which is usually carefully protected by the current and future manufacturers." (TMCnet.com, 17 March 2011) Peter J. Harrington is the founder of Better Pharma Processes, LLC, a consulting firm specializing in pharmaceutical process design and development. From 1988–2008, he worked for the Syntex Technology Center, later Roche Colorado, as a research fellow. Dr. Harrington has more than fifty patents and research publications, including reviews and abstracts, as well as the book Transition Metals in Total Synthesis (Wiley).

Standardizes and expands upon information available in process patents for "blockbuster" drugs

There is a need to inform the public that generic versions of a drug may not be manufactured by the same process as brand-name drugs and that the different processes may have dramatically different environmental impacts. Two global forces are at odds today—the push for "greener" processes and the push for lower drug prices. This book brings this conflict into sharp focus by discussing in detail the published process chemistry for top-selling small molecule drugs.

Providing insights about process route selection, choice of reagents, and reaction conditions, Pharmaceutical Process Chemistry for Synthesis guides process chemists in identifying best processes for manufacturing these blockbuster drugs as they lose patent protection. Further, it highlights the strategies and methodology that might be useful for expediting the process research and development of the blockbusters of the future. Pharmaceutical Process Chemistry for Synthesis also:

• Presents detailed discussions of the published process chemistry of Lipitor®, Advair Diskus®, Prevacid®, Singulair®, Seroquel®, Effexor XR®, Lexapro®, and Actos®
• Aids in the implementation of green chemistry in pharmaceutical manufacturing by comparing and contrasting known multiple processes to the same target
• Summarizes the known process chemistry by discussing the advantages of one selected route for each drug
• Reflects the range of tasks assigned to process chemists—i.e., manufacturing route selection, conversion of an intermediate to final target
• A multi-level table of contents and comprehensive index of reagents for rapid access to specific information

Written from a refreshingly objective perspective, this book is essential for process chemists who need to devise practical syntheses for increasingly complex drugs in a constantly decreasing time frame.

"[This] book contains a wealth of information, taken from the patent literature and from [the author's]decades of experience in process chemistry. Through discussions on route selection [he]introduces practical aspects of route design, including selecting non-toxic, stable and inexpensive starting materials, reactions that minimize impurity contents with optimized yields, and ease of purification. [Dr. Harrington] lays out the various approaches to successful molecules, including biocatalysis, and sorts out which routes are acceptable, creative, likely to be the manufacturing route, or merely holding space.... [This] book will be extremely valuable for the process chemist who wants to delve deeply into details critical for process optimization, and for the student new to chemical process R&D in the pharmaceutical and CRO / CMO industries."
—Neal G. Anderson, Anderson's Process Solutions LLC and author of Practical Process Research & Development