Quinine sulphate pellets for flexible pediatric drug dosing: Formulation development and evaluation of taste-masking efficiency using the electronic tongue

Abstract

The purpose of this study was to develop a taste-masked quinine sulphate dosage form as a flexible pediatric formulation tool. Pellets were produced as they offer more flexibility to body weight dose adaptation and therefore represent an alternative to tablet breaking in pediatrics. Quinine sulphate pellets were produced via extrusion-spheronisation. Next pellets were coated using Eudragit ® E PO to obtain a taste-masked formulation. Using 15% dibutyl sebacate (based on polymer weight) as a plasticizer in the formulation caused rapid pellet agglomeration during storage at 40 °C and 75% relative humidity. Using stearic acid (15% based on polymer weight) as plasticizer yielded pellets which were less sensitive to sticking. Quinine sulphate release in water within the first 5 min of dissolution testing: 9.2%, 5.9% and 2.1% of the drug dose was released from pellets coated with 10%, 20% and 30% (w/w) Eudragit ® E PO, respectively. These observations correlated well with the bitterness score of the formulations determined via the Astree electronic tongue and its Bitterness Prediction Module, showing that 20% (w/w) Eudragit ® E PO was required to obtain a homogeneous film and to delay quinine sulphate release sufficiently to mask the bitterness after drug administration. In acid medium immediate quinine sulphate release was obtained.