Gabriel Lima Barros de Araujo.

A Liga Acadêmica de Ciência de Dados Aplicada é vinculada à Faculdade de Ciências Farmacêuticas da Universidade de São Paulo e aberta para todos graduandos e pós-graduandos da USP.

Pharmaceutical nanocrystals are crystalline drug particles at the nanometer scale that hold great potential in the pharmaceutical industry due to their ability to enhance the solubility and bioavailability of poorly soluble medications. This research project focuses on the production and characterization of axitinib nanocrystals, an antineoplastic drug used in the treatment of advanced renal cell carcinoma. Despite its efficacy, axitinib has low water solubility, which limits its absorption and bioavailability, compromising its clinical effectiveness. To address this challenge, the project proposes using nanocrystal technology, which increases the drug's surface area, resulting in improved dissolution, solubility, and bioavailability.Initially, axitinib will be characterized in its solid state, focusing on properties such as polymorphism, particle size, and thermal behavior. Subsequently, axitinib will be converted into nanosuspensions through high-energy wet milling, using zirconia beads. After production, the nanocrystals will undergo detailed analyses of particle size, zeta potential, thermal behavior, and hygroscopicity, as well as potential polymorphic changes, to ensure the stability of the nanosuspensions. The solubility of the nanocrystals will then be compared to that of the original drug using approaches such as the Crystal16 parallel crystallizer and equilibrium method. The project is expected to provide a robust foundation for developing future formulations that offer more effective antineoplastic treatments with axitinib.

This study aims to investigate the solubility of oxi-chloro telluro anisole, a newly discovered compound with significant therapeutic potential but low water solubility. The low aqueous solubility of drugs is a major challenge for the pharmaceutical industry, as it directly impacts the bioavailability and efficacy of medications. In this context, the creation of amorphous solid dispersions (ASDs) emerges as a promising strategy to enhance the solubility and bioavailability of pharmaceutical compounds.The primary goal of this project is to develop ASDs of the tellurium-based metallodrug by screening polymers that will be used as carriers. To achieve this, the amorphization of the compound will be tested at different concentrations using the solvent evaporation method. Subsequently, the development's efficiency will be evaluated based on the ability to maintain the compound in an amorphous form and increase its solubility. The ASDs will then be characterized using analytical techniques and subjected to solubility tests in physiological pH, laying the groundwork for the future development of formulations that will enable preclinical and clinical studies of the new drug.

In Brazil, snakebites affect around 30,000 people annually, often leading to severe consequences like death or limb amputation. While antivenoms are the standard treatment, new strategies aim to enhance efficacy and reduce side effects. One promising approach is the use of selective peptide inhibitors, such as PPTyr, a serine protease inhibitor from Bothrops jararaca venom, which may reduce local hemorrhage and coagulopathy. This project investigates the physicochemical properties and stability of PPTyr for developing lyophilized formulations in pre-formulation studies.

In Brazil, snakebites affect around 30,000 people annually, often leading to severe consequences like death or limb amputation. While antivenoms are the standard treatment, new strategies aim to enhance efficacy and reduce side effects. One promising approach is the use of selective peptide inhibitors, such as PPTyr, a serine protease inhibitor from Bothrops jararaca venom, which may reduce local hemorrhage and coagulopathy. This project investigates the physicochemical properties and stability of PPTyr for developing lyophilized formulations in pre-formulation studies.

Grant number:23/04534-1Grouped support types:Scholarships abroad - Research Internship - Post-doctorDuration:November 01, 2023 - October 31, 2024Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical TechnologyPrincipal Investigator:Gabriel Lima Barros de AraujoGrantee:Bolaji Charles Dayo OwoyemiSupervisor:Stephen R. Byrn

A piodermite é uma doença comum em cães, causada pela proliferação de Staphylococcus pseudintermedius. O tratamento envolve antimicrobianos como betalactâmicos e fluoroquinolonas, mas o uso indiscriminado favorece linhagens resistentes, exigindo novas alternativas terapêuticas. A rifampicina, eficaz contra Staphylococcus sp., possui limitações como baixa solubilidade, variabilidade de absorção e efeitos adversos. Nosso grupo demonstrou que nanocristais de rifampicina melhoram o desempenho in vitro. Este estudo visa produzir nanocristais em escala piloto, avaliar suas características, estudar a farmacocinética em cães e definir um regime terapêutico. A comercialização pode beneficiar o setor veterinário, criando empregos e oferecendo uma opção para casos resistentes.

The low water solubility issue of antimalarial drugs is a challenge that calls for an urgent improvement and development of new formulations because the limited bioavailability causes the need for high dosages, variability in clinical response, emergence of resistance and efficacy problems. Recent advances in knowledge of crystal engineering present the possibility to design and synthesize higher order cocrystals (HOCs) with improved properties through structural inequivalence and combinatorial approaches, using synthesized binary precursor cocrystal model that allows the inclusion of a molecule with stronger bonding energy. This research aim is to synthesize improved multicomponent pharmaceutical cocrystals of antimalarial drugs as fixed dose combination formulations through structural inequivalence approach using the insoluble antimalarial active pharmaceutical ingredients (APIs) of artermisin quinoline, and antifolate derivatives, such as artemether, primaquine, mefloquine, sulfadoxine etc. Structural inequivalence start with design of stoichiometry binary cocrystal precursor as ABB* from cocrystallization of selected APIs, A + B. Here, the weakly bonded B* situated in more than one crystallographic space (asymmetric unit) i.e. Z' 2 is substituted at bonding point by the inclusion of API (C) that present stronger noncovalent energy, and homologate to a ternary ABC HOC. The successful inclusion of C to design ternary system may require exploiting the chemical differences using the complementarity from combinatorial synthesis, API shape-size mimicry, and synthon hierarchy approaches. Structure-property studies, screening and characterization will be analyzed using X-ray diffraction, spectroscopic techniques, and integrated to acoustic levitator among others. Thermodynamic models and theories on non-covalent interaction such as electron density functions and distance-dependent contacts will aid study of molecular complexity. Finally, drug properties of pharmaceutical interest such as stability, solubility and dissolution of the obtained antimalarial pharmaceutical cocrystals will be investigated. This study is expected to advance the current knowledge in this field, improve supramolecular synthetic approaches, and contribute to the development of better antimalarial formulations.

The pharmaceutical industry widely uses amorphous formulations to improve the low oral bioavailability of many BCS (biopharmaceutical classification system) class II drugs. This project aims to study the local structure of amorphous solid dispersions of poorly soluble drugs, focusing specifically on the structural aspects that may help select polymers that ensure efficient amorphization and allow the development of stable drug formulations. For this purpose, the Pair Distribution Function (PDF) method will be combined with high energy X-ray diffraction analysis obtained via synchrotron light sources to explore the local structure of polymeric ASDs of low solubility drugs. This approach aims to accelerate the development of new, more stable, and soluble drug formulations.

Descrição: Projeto n.º 18/16028-5, aprovado na modalidade Pesquisa Inovativa em Pequenas Empresas / PIPE - Modalidade 1 - Fluxo Contínuo da FAPESP.

Lung cancer is the leading cause of cancer-related death, highlighting the need for strategies to enhance the efficacy of existing treatments. Inhalable chemotherapy is a promising approach to improve drug effectiveness, reduce toxicity, and enhance patient quality of life. This project focuses on developing a dry powder inhalable formulation for the repurposing of flubendazole, a poorly soluble anthelmintic drug with anticancer potential. Flubendazole nanocrystals are obtained through nanoprecipitation and processed via spray drying to optimize aerosolization properties. The goal is to improve pulmonary drug delivery and evaluate its potential as an adjuvant in lung cancer chemotherapy.

Polymorphism can cause quality deviations during the production of medicines and can influence their effectiveness. Therefore, an understanding of this phenomenon and its implications opens a wide field of possibilities to be explored in the pharmaceutical field, including the emergence of new paradigms and tools for the quality assurance of medicines. Small molecule tyrosine kinase inhibitors (TKIs) represent an extremely promising and rapidly expanding group of antitumor drugs given orally. Although some polymorphism information of these compounds is included in the patents, the basic structural and thermodynamic data are poor in terms of quality of the measurements and differences and misconceptions between the crystals forms reported are evident. Additionally, polymorphism is an important factor that can impact the bioavailability and, consequently, clinical efficacy of those compounds, since most of them have low solubility in water. This project falls within this scope and focuses on: (i) preparation of polymorphs, solvates, or co-crystals of TKIs; (ii) their characterization in terms of structure and thermodynamic stability; (iii) their evaluation in terms of biopharmaceutical performance. (AU)