Developing a Commercially Viable Process for an Active Pharmaceutical Ingredient, Challenges, Myths and Reality in the Art of Process Chemistry
Ramesh Yamgar , 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
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.
Article Information
Article History:
Received Date: 18/1/2013
Revision Received Date: 29/3/2013
Acceptance Date: 15/4/2013
Electronic publication date: 31/05/2013
Collection year: 2013
© Yamgar and Sawant; Licensee Bentham Open.
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (
http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
* 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
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Manuscript submitted on 18-1-2013 |
Original Manuscript |
Developing a Commercially Viable Process for an Active Pharmaceutical Ingredient, Challenges, Myths and Reality in the Art of Process Chemistry |