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Synthesis of pioglitazone in batch and capillary microreactor

Grant number: 18/01478-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2018
Effective date (End): March 31, 2021
Field of knowledge:Engineering - Chemical Engineering
Principal Investigator:Mauri Sergio Alves Palma
Grantee:Renan Rodrigues de Oliveira Silva
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Continuous flow microreactors have been used as an alternative over batch reactors due to their advantages, such as excellent heat exchange control due to the high surface/volume ratio, more efficient homogenization due to the small distances for diffusion, leading to increase the rate of chemical reaction, conversion, yield, selectivity and safety when working with reagents and toxic products, reducing waste generation and increasing product purity. Pioglitazone, an oral drug of the family of glitazones, is present in the market under the name of Actos® and mainly combats Type 2 Diabetes Mellitus, one of the biggest concerns in the health area. Effectively introducing Microreactor Technology (TMR) in the national chemical-pharmaceutical industry would enable increased production, reduced costs and increased participation in the world drug market and increased participation in the development of new drugs. This project aims to transpose the synthesis of the drug Pioglitazone from the batch process to the synthesis in a continuous flow and to determine the kinetics and mechanism of the reactions of each step of the synthesis of this drug to be studied. A one-year probationary period is planned for this project at Technical University Kaiserslautern, Germany, under the supervision of Prof. Hans-Jörg Bart, who will assist in the intermediate stages of separation and purification via liquid-liquid extraction. This project is a continuation of the research developed to obtain a master's degree from the University of São Paulo (USP) between August/2015 and August/2017, where one of the stages of Pioglitazone synthesis was extensively studied. This PhD project will be carried out within the scope of the Individual Fapesp 2017/12830-9 funded research grant entitled "Synthesis of Pioglitazone, Rosiglitazone and Lobeglitazone in continuous flow in capillary microreactors" in effect from 01/10/2017 to 30/09/09, 2019, and will count on the collaboration of Prof. Hans-Jörg Bart of the Technical University of Kaiserslautern and Prof. Till Opatz of the Johannes-Gutenberg University of Mainz, Germany. (AU)