Fluconazole: Synthesis and Structural Characterization of Four New Pharmaceutical Cocrystal Forms

Autor(es)

Owoyemi, Bolaji C. Dayo ^[1] ; da Silva, Cecilia C. P. ^[1] ; Souza, Matheus S. ^[2] ; Diniz, Luan F. ^[2] ; Ellena, Javier ^[2] ; Carneiro, Renato L. ^[1]

Afiliação do(s) autor(es)

^[1] Fed Univ Sao Carlos UFSCar, Dept Chem, Rod Washington Luis Km 235, BR-13560905 Sao Carlos, SP - Brazil

^[2] Univ Sao Paulo, Inst Fis Sao Carlos, CP 369, BR-13560970 Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Crystal Growth & Design; v. 19, n. 2, p. 648-657, FEB 2019.
• Citações Web of Science: 3

Resumo

Pharmaceutical cocrystals have emerged over the past several decades as an alternative path for synthesizing stable and/or improved crystalline forms of active pharmaceutical ingredients. In this contribution, we developed a reproducible cocrystallization path for the supramolecular synthesis of four new pharmaceutical cocrystal forms of fluconazole (FLZ), an antifungal multifunctional drug: fluconazole- fumaric acid monohydrate (1:1:1), fluconazole-malic acid (1:1), fluconazole- dipicolinic acid (1:1), and fluconazole-adipic acid (1:1). All the new cocrystals were characterized by powder/single-crystal X-ray diffraction, Raman, Fourier transform infrared spectroscopy, differential scanning calorimetry/thermogravimetric analysis, and hot-stage polarized optical microscopy, and their water solubility was determined. Structurally, although the coformers were different, the same strong O-H center dot center dot center dot N hydrogen bond between the FLZ molecule and the coformers was observed. The aqueous solubility studies revealed that all the cocrystals were found to exhibit improved aqueous solubility when compared to the commercialized FLZ polymorph. (AU)

• Processo FAPESP: 15/25694-0 - Obtenção, caracterização e avaliação de novas formas sólidas cristalinas de fármacos usados no tratamento da tuberculose
• Beneficiário: Luan Farinelli Diniz
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 10/16520-5 - Aplicação de métodos quimiométricos de calibração e resolução multivariada de curvas em espectroscopia Raman para análise qualitativa, quantitativa e de polimorfismo em fármacos
• Beneficiário: Renato Lajarim Carneiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular