Transposition of the synthesis of Pioglitazone from the batch process to flow process in capillary microreactor

• Grant number: 18/21541-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2019
• End date: December 31, 2019
• Field of knowledge: Engineering - Chemical Engineering - Chemical Technology
• Principal Investigator: Mauri Sergio Alves Palma
• Grantee: Paula Almeida Meira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The use of microreactors in chemical-pharmaceutical industries provides a number of advantages because of your reduced size compared to batch reactors, which are more commonly used for this type of industry. These advantages can be associated with the drastic reduction of reaction times, due to the elimination of inefficient mixing effects and the reduction of waste generation causing a lower environmental impact. There is an increase in the mass and heat transfer, which conducts to an easily controllable process, enabling higher efficiency and selectivity. The chemical-pharmaceutical industry is the largest beneficiary of this technology because the microreactors can generate a number of compounds with pharmacological potential, several orders of magnitude higher in comparison to traditional batch process and can decrease in years the time for commercial production of a new drug. Pioglitazone is one of the anti glycemic agents of the glitazone class used to treat diabetes mellitus type 2, and it works like insulin sensitizer in humans. The present work aims at transposing two intermediate reactions of the seven required for the synthesis of Pioglitazone from the usual batch process in chemical industry-pharmaceutical to the flow process in a capillary microreactor. In addition, this work aims to define the best-operating conditions in terms of temperature, solvent, reaction medium total concentration to both processes and also the reaction time in the batch process, which corresponds to the mean residence time in the microreactor, in order to maximize the limiting reactant conversion, product yield, and selectivity. This project will be developed in the context of the research project financed by Fapesp no. 2017/12830-9 entitled "Synthesis of Pioglitazone, Rosiglitazone, and Lobeglitazone in a continuous flow in capillary microreactors" valid from 10/01/2017 to 09/30/2019.