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.

Available technologies on improving the stability of polyphenols in food processing

“…The mechanical methods, such as extrusion/spheronization (Silva et al., 2018), coating or granulation (Andrade, Martins, & Freitas, 2015; Freitas, 2019; Oliveira et al., 2015), and hot melt (Guimarães et al., 2017), are usually applied to large‐size particles or products (Zamarioli, Martins, Carvalho, & Freitas, 2015). In general, smaller particles can be obtained by physicochemical methods such as spray drying (Martins et al., 2013; Nosari, Lima, Serra, & Freitas, 2015; Rocha et al., 2011), spray cooling (Martins, Siqueira, Fonseca, & Freitas, 2014; Pereira, Colombo, Martins, & Pedro de Freitas, 2014), freeze (Ballesteros, Ramirez, Orrego, Teixeira, & Mussatto, 2017) and spray freeze drying (Teixeira et al., 2017), ionic gelation (Cutrim, Alvim, & Cortez, 2019; Pasukamonset, Kwon, & Adisakwattana, 2016; Stoica, Şomoghi, & Ion, 2013; Zam, Bashour, Abdelwahed, & Khayata, 2014), emulsion evaporation, co‐precipitation, and supercritical fluid technology (Munin & Edwards‐Lévy, 2011).…”