Fabrication and characterization of taste-masked core-shell nanofibre mats for dual drug delivery of antihypertensives in pediatrics.

Drug adherence in pediatrics can be challenging due to bitter drug taste, dysphagia and polypharmacy. With pediatric hypertension on the rise worldwide, this study investigated the use of electrospinning to create a novel taste-masked, fixed-dose combination of lisinopril dihydrate (LIS) and amlodipine besylate (AML) for paediatric use. Electrospun nanofibres of the antihypertensives were formulated as core-shell fibres with polyvinylpyrrolidone (PVP), and Eudragit® EPO (EEPO) by applying an electrical charge to a viscous mixture of the drugs, polymers and solvents. The drug loading, release kinetics, morphology, thermal analysis, physical and solid-state characterization of the fibre mats were evaluated. Taste-masking was investigated in vitro by electronic-tongue analysis. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses showed smooth, non-beaded core-shell fibres with diameters in the nanorange. Fourier transform infra-red (FTIR) spectroscopy and x-ray diffraction (XRD) studies confirmed the drugs were amorphously dispersed within the fibres and thermal analysis studies showed acceptable stability profile of the formulations. Both drugs were over 90 % released in 15 mins consistent with immediate release formulations. The e-tongue mean sensor response plot showed the nanofibre mats achieved a statistically significant enhanced taste-masking (p < 0.0001) compared to raw amlodipine which registered a high bitterness reading of 87 mV. This study therefore indicates that coaxial electrospinning may be used to produce a fixed-dose taste masked nanofibre mat of LIS and AML that can potentially be used to improve adherence in children.