title: Improvement of enalapril maleate chemical stability by high shear melting granulation.
abstract: Enalapril maleate is a widely used drug, which is chemically unstable when mixed with excipients resulting in enalaprilat and diketopiperazine as the main degradation products. The preparation of enalapril sodium salt has been used to improve drug stability in solid dosage forms; however, product rejection is observed when the chemical reaction for obtaining the sodium salt is not completely finished before packaging. In this study, granules were prepared by melting granulation using stearic acid or glyceryl monostearate, with a view to developing more stable enalapril maleate solid dosage forms. The granules were prepared in a laboratory-scale high shear mixer and compressed in a rotary machine. Size distribution, flow properties, in vitro drug release and enalapril maleate chemical stability were evaluated and compared with data obtained from tablets prepared without hydrophobic binders. All formulations showed good physical properties and immediate drug release. The greatest improvement in the enalapril maleate stability was observed in formulations containing stearic acid. This study showed that hot melting granulation could be successfully used to prepare enalapril maleate granules which could substitute the in situ formation of enalapril sodium salt, since they provided better enalapril stability in solid dosage forms.
authors.affiliation: a Laboratory of Pharmaceutical Technology , Federal University of Goiás , Goiânia, GO , Brazil and.
authors.forename: Ana Paula Montandon
authors.initials: APM
authors.lastname: de Oliveira
authors.affiliation: a Laboratory of Pharmaceutical Technology , Federal University of Goiás , Goiânia, GO , Brazil and.
authors.forename: Talita Amorim
authors.initials: TA
authors.lastname: Cunha
authors.affiliation: a Laboratory of Pharmaceutical Technology , Federal University of Goiás , Goiânia, GO , Brazil and.
authors.forename: Raphael Caixeta
authors.initials: RC
authors.lastname: Serpa
authors.affiliation: a Laboratory of Pharmaceutical Technology , Federal University of Goiás , Goiânia, GO , Brazil and.
authors.forename: Stephânia Fleury
authors.initials: SF
authors.lastname: Taveira
authors.affiliation: a Laboratory of Pharmaceutical Technology , Federal University of Goiás , Goiânia, GO , Brazil and.
authors.forename: Eliana Martins
authors.initials: EM
authors.lastname: Lima
authors.affiliation: a Laboratory of Pharmaceutical Technology , Federal University of Goiás , Goiânia, GO , Brazil and.
authors.forename: Danielle Guimarães
authors.initials: DG
authors.lastname: Almeida Diniz
authors.affiliation: b Laboratory of Pharmaceutical Processing , University of São Paulo , Ribeirão Preto , SP , Brazil.
authors.forename: Luis Alexandre Pedro
authors.initials: LAP
authors.lastname: de Freitas
authors.affiliation: b Laboratory of Pharmaceutical Processing , University of São Paulo , Ribeirão Preto , SP , Brazil.
authors.forename: Ricardo Neves
authors.initials: RN
authors.lastname: Marreto
keywords: Enalaprilat; diketopiperazine; glyceryl monostearate; hot melt process; stearic acid