The Open Process Chemistry Journal

2013, 5 : 1-10
Published online 2013 May 31. DOI: 10.2174/1875180601004010001
Publisher ID: TOCPCJ-5-1

RESEARCH ARTICLE
 Developing a Commercially Viable Process for an Active Pharmaceutical Ingredient, Challenges, Myths and Reality in the Art of Process Chemistry

Ramesh Yamgar and Sudhir Sawant, *
P. G. Department of Chemistry, Govt. of Maharashtra’s Ismail Yusuf College of Arts, Science and Commerce, Jogesh-wari (East), Mumbai 400 060, India

* Address correspondence to this author at the P. G. Department of Chemistry, Govt. of Maharashtra’s Ismail Yusuf College of Arts, Science and Commerce, Jogeshwari (East), Mumbai 400 060 India; Tel: +919325332034; Fax: +912228744755; E-mail: sawantsudhir@hotmail.com

ABSTRACT

Process development and optimisation studies for the manufacturing process of N-methyl paroxetine was done by applying Quality by Design (QbD) principles. A normal operating range was defined for each process parameter by technique of design of experiments and knowledge of process chemistry to ensure consistent high quality of advanced intermediate and control of impurities. Initial challenges faced during early process development, were overcome by novel approach using polar aprotic solvents like sulpholane. Finally DMSO was used to improve overall impurity profile significantly.We have demonstrated a “ right first time” approach to avoid failures and bitter surprises during scale up in manufacturing plant.

Keywords:

API Process development, process optimisation, negative experiments, critical process parameters, carryover of impurities, reagent stoichiometry.