APPLICATION OF ATOMIC FORCE MICROSCOPY IN THE DESIGN OF SOLID PHARMACEUTICAL FORMS OF EFAVIRENZ

Medicines basically consist of two types of compounds, active ingredients and excipients, whose interactions play a fundamental role in the pharmaceutical formulation and processability. In this context, understanding the interactions between these compounds is of paramount importance to optimize the development of effective formulations. An essential tool for this analysis is the atomic force microscope, which allows the evaluation of surface physicochemical parameters and detailed analysis of the interactions between the components of the formulation, through the functionalization of cantilevers. By correlating these data with other consolidated techniques in the pharmaceutical industry, it becomes possible to enhance the selection of formulation components, reducing the time and costs involved in the development process. The objective of this study is to use Atomic Force Microscopy (AFM) to improve the design process of solid pharmaceutical formulations, taking as reference a commercial formulation developed by FIOCRUZ. Compound samples were deposited on a stainless steel disk for AFM, with fixation by double-sided adhesive tape, resulting in compound tablets. These tablets were characterized by the Peak Force Quantitative Mechanical Property Mapping (PFQNM) mode. We performed adhesion analyzes between the API and the excipient tablets after the functionalization of the cantilevers with crystals of the active ingredient. In addition, we employed methodologies to quantify powder flow properties, including orifice flow and shear cell method. Through the AFM, it was possible to thoroughly evaluate the interactions between the active ingredient and the excipients present in the formulation, exploring their surface adhesive characteristics and scaling them from the least adhesive to the most adhesive with the API. We related these data with the excipients flow analysis methodologies in an isolated and mixed form between IFA-Exc. With this integrated approach, we gained a more complete understanding of the properties of formulation components, providing valuable insights for optimized ingredient selection and improved solid drug development, targeting both therapeutic efficacy and production efficiency.