Study of the mechanochemical synthesis of multicomponent solid forms of gemfibrozil based on in situ PXRD and Raman analyses with synchrotron radiation

• Grant number: 25/07866-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: July 01, 2025
• End date: August 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal Investigator: Flávio Junior Caires
• Grantee: Larissa Loris Silva
• Supervisor: Dr Franziska Emmerling
• Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil
• Institution abroad: Bundesanstalt Für Materialforschung Und -Prüfung, Germany
• Associated to the scholarship: 24/20467-5 - Synthesis, characterization, and evaluation of the physicochemical properties of multicomponent solid forms of Gemfibrozil, BP.IC

Abstract

Gemfibrozil is a widely used drug for the treatment of dyslipidemias, being effective in reducing blood levels of triglycerides and fatty acids, in addition to exhibiting cardioprotective effects. However, gemfibrozil presents limitations in absorption and therapeutic efficacy due to its low solubility in aqueous media, classified as a Biopharmaceutical Classification System (BCS) Class II drug. To overcome these challenges, the project aims to investigate the formation mechanism of the pharmaceutical cocrystal formed by the interaction between gemfibrozil and L-lysine, as well as the pharmaceutical salt formed by gemfibrozil and piperazine, using Time-Resolved In Situ (TRIS) techniques. These new solid forms are being characterized using several techniques, such as thermal analysis, vibrational spectroscopy in the infrared region, and X-ray diffraction. However, to understand the mechanochemical formation mechanisms of certain multicomponent gemfibrozil systems and thereby optimize the synthesis conditions to yield materials with desirable characteristics, in situ real-time (TRIS, time-resolved in¿situ) XRD and Raman analyses using synchrotron radiation will be conducted during the BEPE internship. This is a powerful approach that is not yet available or adapted for mechanochemical synthesis studies in Brazil. The in situ XRD and Raman analyses using synchrotron radiation will enable real-time monitoring of structural changes, contributing to a detailed understanding of the formation and stability of new solid phases during the process. Additionally, SEM and EDS techniques will be used to observe morphological changes, particle size, and composition during the mechanochemical process, which can support the understanding of multicomponent system formation, as well as provide data for appropriate particle size and shape control, key features in drug development. Therefore, the combination of these techniques will allow for an in-depth study of the formation and characterization of new gemfibrozil solid systems, contributing to the development of pharmaceutical forms with enhanced solubility and, consequently, improved therapeutic performance. (AU)