Micro-reactors in the synthesis of pharmaceuticals

• Grant number: 14/07757-2
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2014
• End date: February 28, 2017
• Field of knowledge: Engineering - Chemical Engineering - Chemical Technology
• Principal Investigator: Mauri Sergio Alves Palma
• Grantee: Mauri Sergio Alves Palma
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Ardson dos Santos Vianna Junior ; Roberto Parise Filho

Abstract

Microreactors offer excellent heat and mass transfer, high surface/volume ratio with laminar flow and without axial dispersion. Microreactor 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, intensive chemical processes and reactions with very dangerous, toxic or explosive chemicals. 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 microreactor to produce organic molecules with pharmacological potential which have been synthesized in batch processes in the Department of Pharmacy, School of Pharmaceutical Sciences-USP, determine the kinetics of those reactions, determine the best operating conditions for each synthesis and develop the mathematical model of the process. This work will be accomplished in collaboration with Prof. Ardson dos Santos Vianna Jr., Department of Chemical Engineering, School of Engineering, University of São Paulo, which has the microreator and will be responsible for the fluid dynamic studies and mathematical modeling of the process and Prof. Roberto Parise Filho, Department of Pharmacy, School of Pharmaceutical Sciences-USP, who will help with the procedures of synthesis, chemical analyses of the compounds derived from the Thiazolidine-2,4-dione and analysis of the results of the reactions of the Thiazolidine-2,4-dione. This project also has the support of Prof. Hélio Alexandre Stefani, Department of Pharmacy, School of Pharmaceutical Sciences-USP and the infrastructure of his laboratory, , who will help with the procedures of synthesis, chemical analyses of the compounds derived from the Indol and analysis of the results of the reactions of the Indol. Prof. Hélio cannot currently be contributor of this project, as it does not have availability of time, in view of research projects that are in progress under his coordination. (AU)

Scientific publications

(6)

(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. (13/07914-8, 17/12830-9, 14/07757-2)

PINHEIRO, DANILO DA SILVA; DE OLIVEIRA SILVA, RENAN RODRIGUES; CUESTA CALVO, PAULO VICTOR; DA SILVA, MILENA FERNANDES; CONVERTI, ATTILIO; ALVES PALMA, MAURI SERGIO. Microreactor Technology as a Tool for the Synthesis of a Glitazone Drug Intermediate. CHEMICAL ENGINEERING & TECHNOLOGY, v. 41, n. 9, p. 1800-1807, SEP 2018. (14/07757-2)

SANTANA, HARRSON S.; HADDAD, VICTORIA A.; CALVO, PAULO V. C.; PALMA, MAURI S. A.; SILVA, ADRIANO G. P. DA; NORILER, DIRCEU; TARANTO, OSVALDIR P.; SILVA, JOA O L.. Design, optimization and scale-up of a new micromixer design based on plate column for organic synthesis. CHEMICAL ENGINEERING JOURNAL, v. 446, p. 14-pg., 2022-10-15. (14/07757-2, 16/20842-4)

VIEIRA, RODRIGO DE OLIVEIRA; SILVA JR, JOAO LAMEU; MEIRA, PAULA ALMEIDA; BRESSAN, GABRIEL LIMA; CALVO, PAULO VICTOR CUESTA; SANTANA, HARRSON SILVA; PALMA, MAURI S. A.. Experimental and numerical investigation of the reaction of 2,4-thiazolidinedione and p-methoxybenzaldehyde in microreactors for the production of drugs for diabetes mellitus type 2 treatment. CANADIAN JOURNAL OF CHEMICAL ENGINEERING, v. N/A, p. 16-pg., 2023-05-08. (16/20842-4, 14/07757-2)

SILVA JR, JOAO LAMEU; CALVO, PAULO VICTOR CUESTA; PALMA, MAURI S. A.; LOPES, MARIANA G. M.; SANTANA, HARRSON SILVA. Process intensification in flow chemistry using micro and millidevices: Numerical simulations of the syntheses of three different intermediate API compounds for diabetes mellitus drug production. CHEMICAL ENGINEERING RESEARCH & DESIGN, v. 205, p. 12-pg., 2024-04-16. (16/20842-4, 14/07757-2)

DE OLIVEIRA SILVA, RENAN RODRIGUES; CUESTA CALVO, PAULO VICTOR; DA SILVA, MILENA FERNANDES; SOLISIO, CARLO; CONVERTI, ATTILIO; ALVES PALMA, MAURI SERGIO. Flow Synthesis of a Thiazolidine Drug Intermediate in Capillary Microreactors. CHEMICAL ENGINEERING & TECHNOLOGY, v. 42, n. 2, p. 465-473, FEB 2019. (14/07757-2)