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Synthesis of Pioglitazone, Rosiglitazone and Lobeglitazone in continuous flow in capillary microreactors

Grant number: 17/12830-9
Support type:Regular Research Grants
Duration: October 01, 2017 - June 30, 2020
Field of knowledge:Engineering - Chemical Engineering
Principal Investigator:Mauri Sergio Alves Palma
Grantee:Mauri Sergio Alves Palma
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers: Sylvio Jorge Hares Junior


Microreactors offer excellent heat and mass transfer, high surface/volume ratio with laminar flow and without axial dispersion. Microreactors have been used in the continuous-flow synthesis of pharmaceuticals, creating chemical libraries of compounds with pharmacological potential, continuous synthesis in multiple steps, particularly for rapid reactions that involve much heat, chemical process intensification and with chemical reactions where dangerous, toxic or explosive chemicals are present. Some advantages of drug synthesis in microreactors are the drastic reduction of reaction times, due to the elimination of inefficient mixing effects, increased yield and selectivity of the reactions and reduction of waste generation. The Chemical-Pharmaceutical Industry is the largest beneficiary of this new technology, because the microreactors can generate a number of compounds with pharmacological potential, several orders of magnitude greater than in traditional batch process, can lessen in years the time for commercial production of a new drug and can be extremely small and compact industrial units. This work aims at using a system of microreactors to produce the APIs Pioglitazone (Actos®), Rosiglitazone (Avandia®) and Lobeglitazona (Duvie®) for the first time in continuous flow process, determining the kinetics of those reactions, and the best operating conditions for each synthesis. This project will be developed in collaboration with Profs. Till Opatz (Johannes Gutenberg-University Mainz, Germany) who idealized the synthetic routes of the APIs, and Prof. Hans-Joerg Bart (Technical University of Kaiserslautern, Germany) who developed the purification processes of the intermediate products by liquid-liquid extraction in micro devices. (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)
SIGUEMOTO, ERICA S.; LEITE RECHE, LEANDRO; GUT, JORGE A. W.; PALMA, MAURI S. A. Residence Time Distribution of a Capillary Microreactor Used for Pharmaceutical Synthesis. CHEMICAL ENGINEERING & TECHNOLOGY, v. 43, n. 3 JAN 2020. Web of Science Citations: 0.

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