Crystal Engineering applied to pharmaceuticals aiming developing new designs via supramolecular synthons: improvement of physicochemical and biopharmaceutical properties to implement, in Brazil, a Pharmaceutical Center for Technological Innovation

• Grant number: 24/18554-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2025
• End date: February 29, 2028
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Javier Alcides Ellena
• Grantee: Cecilia Carolina Pinheiro da Silva
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

This research project "Crystal Engineering applied to pharmaceuticals aiming developing new designs via supramolecular synthons: improvement of physicochemical and biopharmaceutical properties to implement, in Brazil, a Pharmaceutical Center for Technological Innovation" aims to obtain new salts and/or drug-drug cocrystals capable of offering pharmacokinetic and pharmacodynamic improvements in relation to their separately administered inputs, the generation of technological innovation accessible to the country with an emphasis on the importance of the Unified Health System, the acquisition of regulatory knowledge of analyzing new materials to insert them effectively in Brazil in order to create in the country, in the hopefully not so distant future, a robust innovation system, capable of balancing public and private interests , in addition to intellectually promoting pharmaceutical industries so that they are able to respond more quickly to public health emergencies and with autonomy. Initially, attention will be paid to drugs belonging to classes II and IV of the Biopharmaceutical Classification System (BCS), which are drugs that present problems regarding solubility and permeability. The new multicomponent solid forms will be characterized by single-crystal and powder X-ray diffraction, vibrational infrared spectroscopy by Fourier transform and Raman scattering, thermogravimetric analysis and differential scanning calorimetry. Once identified and characterized, the new pharmaceutical solids will be evaluated for their bioavailability, and this step must be carried out during an internship abroad, in an institution capable of fully teaching this technique, which involves steps of solubility, dissolution, toxicity and permeability, in vivo and in vitro. Among the options, it is specifically expected that such an internship can be established at the University of Michigan (USA), where the BCS was created in 1995, aiming to learn as much as possible about all the regulatory steps for approval of drug- drug salts and cocrystals for insertion into the market, considering that in Brazil such legislation is still incomplete and no compound of this type has yet been approved for use. The result of the project is expected to obtain new crystalline forms with advantages over current drugs, with regard to physicochemical and pharmacokinetic parameters, in addition to bringing high-impact publications, patents, but above all knowledge to implement at the São Carlos Physics Institute, within the Multi-User Structural Crystallography Laboratory (LaMuCrEs), in the near future, the space for pharmacokinetic and pharmacodynamic studies. Together with all the infrastructure that LaMuCrEs already has for the analysis of new crystalline materials, the possibility of developing such pharmacokinetic and pharmacodynamic analyzes in the same location will enable the implementation, at the University of São Paulo, of the first Brazilian Pharmaceutical Center for Technological Innovation aimed at to develop innovative technologies in order to solve the main challenges faced by the Pharmaceutical and Biopharmaceutical Industry, in an efficient and personalized way.