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Introduction to Photostability
A Practical Introduction to
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Process Research in the Pharmaceutical Industry: The Design and Development of Practical Syntheses
| Type | Course |
|---|---|
| Language | English |
| Date |
August 17, 2009
to August 18, 2009 |
| Venue |
Four Points By Sheraton 1201 K Street NW Washington, DC 20005 US |
| Chemistry Specialties |
|
| Chemistry Techniques |
|
| Contact |
American Chemical Society 1155 Sixteenth Street, NW Washington, DC 20036 US (800) 227-5558 shortcourses@acs.org |
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This course on pharmaceutical process research will focus on the design and development of practical syntheses for product candidates. The importance of combining synthetic organic chemistry with physical/mechanistic organic chemistry and innovation is stressed. It is designed to expose participants to all phases of drug process development, from preclinical to New Drug Application filing. Numerous examples will be used to illustrate key aspects of process research, including issues related to US Good Manufacturing and Good Laboratory Practices (cGMP/GLP), as well as those related to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). Real life examples will address creativity, timeline, economic, environmental, analytical, formulation, final form, cGMP, impurity, and regulatory issues.
Key Topics
* Process Issues
* Asymmetric Hydrogenations
* Phase Transfer Chemistry
Speakers
Drs. Ulf Dolling and Edward Grabowski have spent their entire careers in the Merck Research Laboratories Process Research Group. Dr. Dolling (B.S. Univ. of Hamburg, Ph.D. Rutgers) was Executive Director of Process Research prior to his retirement in 2005. Dr. Grabowski (B.S. MIT, Ph. D. Univ. of Rochester) was Vice President of Chemistry in Process Research at his retirement. They have co-authored more than 150 scientific papers and reviews deriving from their work in process research. They have been co-inventors on more than 70 US patents.
Session titles
* Introduction and Overview - What is Process Research? Process research viewed through the lens of innovation.
* Process Issues - Overview of cGMP/GLP and ICH guidelines and their application from early development to NDA filing. Selection of GMP starting materials. Management of impurity profiles during the development cycle. The interface of process chemistry and pharmaceutical formulation: API (bulk drug) and drug product—particle size distribution and surface area, purity, crystal form (polymorphs), and sterile products.
* Modern innovative chemistry – Handling complex molecules in chemical development of drug candidates, such as anti-methicillin-resistant staphylococcus aureus (MRSA) carbapenem and INVANZ® (ertapenem) antibiotics.
* Crystallization - Fundamentals of crystallizations: supersaturation, nucleation, and crystal growth. Effect of crystallization processes on API properties with real life examples.
* Asymmetric Hydrogenations – The philosophy and role of asymmetric hydrogenations in process research with applications to the preparation of process intermediates and an anthrax lethal factor candidate.
* Phase Transfer Chemistry – Development of an industrial asymmetric phase transfer catalysis for the diuretic Indacrinone. Improved efficiency by a novel dual catalysis.
* Acetylide Chemistry – Enantioselective additions of acetylides to prochiral imines and ketones mediated by chiral aminoalkoxides – basic research studies and application to the efavirenz (Sustiva® and Stocrin®) manufacturing process.
* Proscar® (finasteride) development chemistry – From medicinal chemistry to a economical manufacturing process. New dehydrogenation processes. Control of polymorphs and particle size distribution via jet mix crystallization.
* Nucleoside Chemistry – Development of a candidate for the treatment of hepatitis C. Special problems in chemical development of nucleoside candidates.
* Fluoroalanine Chemistry – The challenge of a small molecule with an apparent impossible medicinal chemistry route. Efficient deuterium use by resolution via preferential crystallization vs racemization/recycle processes.
* Green Chemistry Strategies - Applications of diasteriomeric and asymmetric hydrogenations as well as crystallization induced diastereomeric transformations in the development of green chemical processes. JanuviaTM (sitagliptin phosphate) and Emend® (aprepitant).
* Development examples – Development of a practical process for the preparation of the Corey-Itsunu oxazaborolidine catalyst and applications in the preparation of ophthalmic candidates. NK-1 Receptor Antagonist and the evolution from a long linear, resolution based synthesis to a short, diastereoselective synthesis.
* Resolutions vs Enzymes vs Asymmetric Hydrogenations - Strategies in chemical development – the odyssey of the development of the process for cholesterol-lowering drug candidate MK-524.