Synthesis, caracterization and structural elucidation of Lopinavir pharmaceutical cocrystals

• Grant number: 24/07156-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• End date: August 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal Investigator: Flávio Junior Caires
• Grantee: André Luis de Almeida
• Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil

Abstract

Viral diseases, from common respiratory infections to serious illnesses such as AIDS, pose public health challenges. The use of antiretrovirals is essential to contain these diseases, offering a better quality of life to patients. Protease inhibitors (PIs) are a class of antiretrovirals used to treat HIV, but they have disadvantages such as low bioavailability, which requires administration in high doses and can result in serious side effects. Lopinavir, the drug used in this study, is an antiretroviral that faces similar challenges, requiring improvements in its formulation to ensure efficacy and reduce the risk of side effects. One of the strategies to improve the physicochemical properties of Lopinavir will be the formation of pharmaceutical cocrystals, which are defined as multicomponent solids that are constituted by a drug and a suitable coformer in a specific stoichiometric proportion. The objective of the work will be to improve the solubility and bioavailability of Lopinavir through the prospecting of cocrystals using mechanochemical methods and crystallization in solution using different solvents. Crystal engineering will be crucial for the development of this study, with the use of software such as ConQuest and Mercury, integrated with the Cambridge Structural Database (CSD), which enable the identification of synthons (region of molecular interactions, between the drug and coformer, such as hydrogen bonds and À-À interactions) and facilitating rational planning in defining the ideal coformers for the formation of cocrystals.