Preparação e caracterização de complexo de inclusão entre trimetoprim e 2-hidroxipropil-gama-ciclodextrina

• Autor(a) principal: Macedo, Osmir Fabiano Lopes de
• Data de Publicação: 2010
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFS
• Texto Completo: https://ri.ufs.br/handle/riufs/6129
• topic: Química física; Solução aquosa; Tratamento de infecções; Trimetoprim; Hidroxipropil-gama-ciclodextrina; Complexo de inclusão; Physical chemistry; Aqueous solution; Infections - treatment; Trimethoprim; Hydroxypropyl-gamma-cyclodextrin; Inclusion complex; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA

This work involved the preparation and characterization of an inclusion complex of Trimethoprim (TMP) a drug used in the treatment of infections and hydroxypropylgamma- cyclodextrin (HP-γ-CD). Owing to the low aqueous solubility of this drug, high dosages are required to provide a satisfactory therapeutic effect, although this also brings severe side effects to some patients. Thus here we aimed to increase the TMP aqueous solubility in order to potentially reduce the side effects by complexation in a CD derivative. Prior to the inclusion study, some relevant physiochemical parameters of the drug such as pKa, solubility in several pH values as well as absorption coefficient were determined. The inclusion complex has been prepared by the suspension method and collected by lyophilization. Primary evidence of the inclusion of TMP in HP-γ-CD was provided by the increase of the solubility in presence of HP -γ - CD, from the phase-solubility diagram obtained at different temperatures and pH values. The apparent stability constants K 1:1 for the complex formed at different temperatures and pH values were found strongly depend on the conditions, being higher at low pH. A 1:1 stoichiometry was suggested for the complex both from the phase-solubility diagram and from the continuous variation method Additional evidences of the inclusion were provided by thermal analysis (DSC), which suggested that TMP is not present in the sample as an isolated crystalline solid. The XRD analysis evidenced the loss of the TMP crystalline character in the complex, which is commonly observed for CD complexes but may be also a consequence of the lyophilization process. The presence of bands characteristic of both species was observed in the infrared spectrum of the complex. Although differences observed in the relative intensities cannot directly evidence complex formation, they don t exclude this possibility. Direct evidence of TMP inclusion in the CD cavities were given from 1H-1H bidimensional ROESY spectrum, which also showed that the inclusion mode involves penetration of the trimethoxyphenyl group in HP-γ-CD.