RESUMEN
OBJECTIVES: The purpose of this study was to investigate the potential of hot-melt extrusion (HME) for masking the taste of bitter active pharmaceutical ingredients (APIs) when incorporated into different polymer formulations. METHODS: Extrudates were produced by HME using two water soluble cationic model drugs (cetirizine HCl and verapamil HCl) processed with various grades of anionic polymers (Eudragit L100 and Eudragit L100-55 (Acryl EZE)). The process was optimised by using a single screw extruder to produce extruadates with the desirable characteristics. KEY FINDINGS: In-vivo results obtained from a panel of six healthy human volunteers demonstrated that the HME extruded formulations improved the taste significantly compared with that of the pure APIs. In addition, an in-vitro evaluation carried out by an Astree e-tongue equipped with seven specific sensors demonstrated significant taste improvement of the extrudates compared with placebo polymers and the pure APIs. Furthermore, the extrudates characterised by SEM, X-ray and differential scanning calorimetry studies showed the existence of molecularly dispersed APIs while in-vitro dissolution showed fast release for all drug substances. CONCLUSIONS: HME can effectively be used to mask the taste of bitter APIs by enhancing drug-polymer interactions.
Asunto(s)
Cetirizina/administración & dosificación , Portadores de Fármacos , Composición de Medicamentos/métodos , Calor , Ácidos Polimetacrílicos/química , Gusto , Verapamilo/administración & dosificación , Resinas Acrílicas/química , Adolescente , Adulto , Cetirizina/química , Portadores de Fármacos/química , Estabilidad de Medicamentos , Femenino , Congelación , Humanos , Masculino , Cooperación del Paciente , Solubilidad , Verapamilo/química , Adulto JovenRESUMEN
The purpose of this study was the in vitro and in vivo evaluation of the masking efficiency of hot melt extruded paracetamol (PMOL) formulations. Extruded granules containing high PMOL loadings in Eudragit EPO (EPO) or Kollidon VA64 (VA64) were prepared by hot-melt extrusion (HME). The taste masking effect of the processed formulation was evaluated in vivo by a panel of six healthy human volunteers. In addition, in vitro evaluation was carried out by an Astree e-tongue equipped with seven sensors. Taste sensing technology demonstrated taste improvement for both polymers by correlating the data obtained for the placebo polymers and the pure APIs alone. The best masking effect was observed for VA64 at 30% PMOL loading. The e-tongue results were in good agreement with the in vivo evaluation. In vitro dissolution of the extruded granules showed rapid PMOL releases.