Synthesis, characterization, structural determination, and solubility evaluation of cocrystals of dapsone and clofazimine

• Grant number: 25/02526-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2025
• End date: June 30, 2028
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Fabio Furlan Ferreira
• Grantee: Patrícia Osório Ferreira
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Low aqueous solubility is one of the factors that hinders the launch of new drugs, as well as the efficacy of drugs already on the market. Strategies to improve this property include multicomponent pharmaceutical systems, including cocrystals, which have shown promise in improving several physicochemical properties. Cocrystals do not present new chemical bonds but rather intermolecular interactions, such as hydrogen interactions, which maintain the pharmacological activity of the active ingredient(s). For this study, two antibiotics with low aqueous solubility were chosen - dapsone and clofazimine - both used in the treatment of leprosy, a neglected disease endemic to Brazil, which, despite being a curable disease, still has great stigma. Since its discovery, the treatment for leprosy has not received any further development, which has led to problems such as bacterial resistance. Mechanochemical grinding will be used to synthesize cocrystals, which consists of grinding in a vibrating ball mill. This method is recognized for using little or no solvent, which aligns with the principles of green chemistry. Thermal analysis will be used to characterize the systems obtained to evaluate their physical and chemical properties, and infrared spectroscopy and X-ray diffractometry will be used to assess the structures obtained. Solubility and dissolution rate tests will also be performed to determine whether there was an improvement compared to isolated drugs. Obtaining cocrystals of these drugs represents a significant advance in the treatment of diseases such as leprosy, but not only that, since these drugs can also be used to treat other bacterial infections and, considering the increase in bacterial resistance, obtaining new antibiotic formulations is extremely necessary. (AU)