Desenvolvimento de complexos de inclusão sólidos contendo carvedilol e ciclodextrina pelas técnicas de leito fluidizado e spray drying

• Autor(a) principal: Alonso , Ellen Cristine Pineze
• Data de Publicação: 2016
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/0013000008c1h
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/7019
• topic: Carvedilol; Ciclodextrina; Spray drying; Leito fluidizado; Carvedilol; Cyclodextrin; Spray drying; Fluid-bed; CIENCIAS DA SAUDE::FARMACIA

Introduction: Cyclodextrins have been used in several industries segments, mainly in the pharmaceutical industry. This material has been employed in the complexation of poorly soluble drugs with the aim to increase bioavailability and effect. Carvedilol (CARV) is a poor soluble drug used in the treatment of hypertension and congestive heart failure. Its oral bioavailability is reduced to β5%, due to their low aqueous solubility and first pass effect. Because of this, it is an excellent choice to form inclusion complexes with cyclodextrins. However, the use of cyclodextrins have some limitations, once it is necessary to use a large amount in the formulation and it can cause dilution of the drug and it can result in a solid oral form with inappropriate dimensions. Therefore, different strategies have been used to enhance complexation efficiency and reduce the amount of cyclodextrin, like the combination of the effect of drug ionization and inclusion complexes. In addition, the choice of the technique used to produce inclusion complexes is very important, because it is necessary to develop economic and effective techniques, which have been easily scalable to produce inclusion complexes in the industry. Spray drying technique have been extensively studied in cyclodextrin complexation, but this method is very expensive and presents lower efficiency. On the other hand, fluid-bed granulation has been widely used in the production of solid dosage forms but the use of this technique to produce cyclodextrin inclusion complexes is not described in the literature. Objective: The purpose of this study is to produce and characterize inclusion complexes containing carvedilol and cyclodextrin, using spray drying and fluidized bed techniques, with the aim to enhance drug dissolution rate. Material and methods: Phase solubility studies were performed using various cyclodextrins, in pH 1,β and 6,8, at room temperature, during 48 hours. Binary complexes were produced by spray drying and fluidized bed techniques. FTIR spectroscopy, DSC analysis, morphology, particle size, flowability and dissolution studies were performed to characterize the inclusion complexes. Results and discussion: Hidroxypropyl--cyclodextrin Cavitron W7 HP7 had the better solubility results. Thus, binary complexes CARV: HPCD prepared by spray drying and fluidized bed techniques in pH β,β showed better results and dissolution rate was 7 and 6 folds, respectively. However, solid dispersion prepared by fluid-bed presented better flowability indicating that this technique is the most appropriate for a large-scale production of solid dosage forms. Additionally, complexes containing HPȖCD showed good dissolution rate and could be considered as one more option for CARV complexation with great performance of inclusion complex formation in solid state.