Desenvolvimento de complexos de inclusão sólidos contendo carvedilol e ciclodextrina pelas técnicas de leito fluidizado e spray drying
Nenhuma Miniatura disponível
Data
2016-03-31
Autores
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Federal de Goiás
Resumo
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: HPCD 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.
Descrição
Palavras-chave
Citação
ALONSO, E. C. P. Desenvolvimento de complexos de inclusão sólidos contendo carvedilol e ciclodextrina pelas técnicas de leito fluidizado e spray drying. 2016. 75 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2016.