EXCIPIENT COMPATIBILITY STUDY BETWEEN COMBINED FIXED DOSE ANTITUBERCULOSTATIC DRUG AND POLYMERIC HYDROGELS

• Grant number: 25/16107-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
• Principal Investigator: Caio Marcio Paranhos da Silva
• Grantee: Felipe Eduardo de Souza
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Pulmonary tuberculosis (TB) is the most prevalent neglected disease in Brazil. It is estimated that approximately 103,000 people present symptoms associated with TB each year, with a death toll of approximately 12,000 people. The recommended and agreed upon treatment is based on the administration of antibiotics in fixed-dose combinations (FDCs), including the following drugs: rifampicin, isoniazid, ethambutol and pyrazinamide. One of the harmful characteristics of the therapeutic approach to TB is the prolonged treatment, which in most cases lasts for approximately four to six months. Consequently, one of the main factors for non-adherence to treatment is abandonment of the treatment, which can result in the patient's relapse while also favoring the emergence of bacterial strains that are more resistant to the prescribed antibiotics. This situation is aggravated when considering pediatric treatment, where, in addition to the factors listed above, difficulty in swallowing and poor palatability may be included. Therefore, more efficient pharmaceutical forms regarding adherence to therapy are imperative to reduce the numbers associated with TB in Brazil. One of the opportunities is the use of controlled release systems. Although several studies have previously demonstrated the potential of these systems in the controlled delivery of antibiotics in TB therapy, the vast majority consist of high added value devices, such as nanostructures and liposomal vesicles, which makes the development of pharmaceutical forms for neglected diseases unfeasible. The present proposal aims to contribute to this scope by preliminarily evaluating the drug-excipient compatibility between DFCs for TB and hydrogels based on polyvinyl alcohol and sodium alginate. Both polymers are recognized as biocompatible and biodegradable, with applications in several areas of medicine and pharmaceutical technology, in addition to presenting low cost. Therefore, the aim is to evaluate whether the compatibility between the drug and the polymeric excipients can open an opportunity for the subsequent development of controlled release systems aimed at TB therapy with high adherence, both for adults and pediatric patients. The study will focus on thermal analysis, via DSC and TGA, in addition to infrared spectroscopy and X-ray diffraction to identify the interactions present between the components, in addition to verifying the short- and long-term stability and the kinetic profile of drug release.