Desenvolvimento e caracterização de dispersão sólida para potencial aumento de solubilidade de metotrexato

• Ano de defesa: 2024
• Autor(a) principal: Almeida, Josué Malaquias De
• Orientador(a): Carvalho, Flávia Chiva
• Banca de defesa: Trevisan, Jerusa Simone Garcia, Bonfilio, Rudy
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Alfenas
• Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências Farmacêuticas
• Departamento: Pró-Reitoria de Pesquisa e Pós-Graduação
• País: Brasil
• Palavras-chave em Português: Metotrexato; Solubilidade; Classe IV; Dispersão sólida; Método de preparação
• Área do conhecimento CNPq: CIENCIAS DA SAUDE::FARMACIA
• Link de acesso: https://repositorio.unifal-mg.edu.br/handle/123456789/2844

Introduction: Methotrexate (MTX) is widely used in the treatment of autoimmune diseases and cancers but faces challenges due to its low solubility and permeability, limiting its oral bioavailability. Although solid dispersion is a common method for improving drug solubility, its effectiveness for MTX remains underexplored. Objective: This study aimed to develop and evaluate MTX solid dispersions to increase its solubility through induced amorphization. Methods: Amorphous MTX solid dispersions were prepared with the polymers Poloxamer 407, PVP-K30, and PEG6000 using the solvent evaporation method. Characterization was conducted via differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FTIR) to confirm amorphization. A UV spectrophotometry analytical method was developed and validated for the solubility test, which was conducted in pH 6,8 phosphate buffer, comparing the dispersions with free MTX and corresponding physical mixtures. Results: The PXRD analyses indicated amorphization of MTX in one dispersion, however, its structural change in another dispersion needs additional analysis for confirmation. The validated analytical method demonstrated linearity, precision, and accuracy within regulatory limits. Solubility tests showed that amorphous MTX solid dispersions did not increase solubility relative to the free drug, suggesting that amorphization alone may not improve MTX solubility. This finding aligns with previous studies that observed minimal solubility gains with solid MTX dispersions in crystalline form and in the amorphous state. Conclusion: The results suggest that while amorphous MTX solid dispersions are feasible, they may not provide a significant solubility advantage. Alternative approaches, such as nanoencapsulation, may offer more effective solutions for improving MTX bioavailability, guiding future research in drug delivery systems.