Synthesis of pioglitazone in batch and capillary microreactor

• Grant number: 18/01478-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2018
• End date: April 30, 2023
• Field of knowledge: Engineering - Chemical Engineering - Chemical Technology
• Principal Investigator: Mauri Sergio Alves Palma
• Grantee: Renan Rodrigues de Oliveira Silva
• Host 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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CUESTA CALVO, PAULO VICTOR; BATISTA, PATRICK RODRIGUES; DE OLIVEIRA SILVA, RENAN RODRIGUES; CONVERTI, ATTILIO; AL ARNI, SALEH; SOLISIO, CARLO; DUCATI, LUCAS C.; ALVES PALMA, MAURI SERGIO. Flow Synthesis of 2-[Methyl(pyridin-2-yl)amino]ethanol: An Experimental and Computational Study. CHEMICAL ENGINEERING & TECHNOLOGY, v. 44, n. 2, DEC 2020. (18/07308-4, 17/12830-9, 18/26717-2, 20/10246-0, 18/01478-5, 17/17750-3)

SILVA, RENAN RODRIGUES DE OLIVEIRA; CALVO, PAULO VICTOR CUESTA; MERFELS, CHRISTIAN ADRIAN; LIMA, MIKAEL VITOR RODRIGUES; SANTANA, HARRSON S.; CONVERTI, ATTILIO; PALMA, MAURI SERGIO ALVES. Synthesis of Lobeglitazone intermediates seeking for continuous drug production in flow capillary microreactor. JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY, v. 116, p. 11-pg., 2022-10-25. (18/01478-5, 17/12830-9, 18/26717-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Renan Rodrigues de Oliveira. Synthesis of Pioglitazone and Lobeglitazone in batch and capillary microreactor. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.