Pesquisa, desenvolvimento e caracterização de comprimidos contendo entacapone, carbidoba e levodopa
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Data
2012-09-28
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Universidade Federal de Goiás
Resumo
Entacapone is a catechol-o-methyl transferase inhibitor used in association with
carbidopa and L-dopa in the treatment of Parkinson’s disease. Currently, only
one medication containing the association of these three substances is available
on the market and it is under patent protection. The objectives of this study were
the development and the physicochemical characterization of tablets containing
the association of entacapone, carbidopa, and L-dopa using Stalevo® as a
reference medication. The evaluation of possible incompatibilities between
entacapone, carbidopa, L-dopa, and the excipients was carried out as a preformulation
step. To achieve this, initially, differential scanning calorimetry (DSC)
analyses were performed and, posteriorly, additional confirmatory studies were
conducted using Fourier transformation-infrared spectroscopy (FTIR) and optical
microscopy. The tablets were developed using the wet granulation method and
the wet granulation method in a high shear mixer and physicochemical
parameters were evaluated both for the granulate (moisture, density, and flow)
and the oral dosage forms developed (friability, hardness, average weight,
disintegration, and content of active ingredient). The dissolution profile of the
tablets obtained was assessed based on Stalevo®. Tablets containing
entacapone should contain pharmacotechnical elements to promote its
bioavailability, since it presents low solubility and low permeability. Therefore, for
the development of tablets, different batches were produced using surfactants.
Entacapone associated with carbidopa, magnesium stearate, and crospovidone
presented signs of degradation, according to FTIR and microscopy. Thus, these
excipients should be avoided in the development of solid dosage forms
containing entacapone. The batches of core tablets developed during this study
were approved regarding the physicochemical criteria, including the dissolution
profile. The coated tablets containing poloxamer 407 presented dissolution
profile similar to the reference medication.
Descrição
Palavras-chave
Entacapone , DSC , FTIR , Comprimidos , Dissolução , Entacapone , DSC , FTIR , Tablets , Dissolution
Citação
RODOVALHO, Luciana Ferreira Fonseca. Pesquisa, desenvolvimento e caracterização de comprimidos contendo entacapone, carbidoba e levodopa. 2012. 163 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Goiás, Goiânia, 2012.