HME coupled with FDM 3D printing of a customized oral solid form to treat pediatric epilepsy

Interest in hot-melt extrusion (HME) and fused deposition material (FDM) printing has increased in recent years, for the production of tailored medications for patients with specific requirements, such as pediatrics. Liquid forms are often preferred for children but these forms are less stable than oral solid forms (such as tablets or powder), requiring preservative not always suitable for children. Then, the aim of this study is to develop a dose- adapted dispersible 3D printed forms using HME with FDM to treat pediatric epilepsy. Polyethylene oxide (PEO)based 3D printed forms were developed with sodium valproate (VAL) as model drug at different concentrations. The effects of polyethylene glycol (PEG)'s molecular weight (PEG6K and PEG35K) used as plasticizer on the formulations' mechanical, thermal and rheological properties were investigated. Formulation with 10 % (w/w) of VAL were printed with PEG6K and PEG35K, while only PEG35K was suitable for extruding and printing a formulation containing 30 % (w/w) of VAL due to its rheological properties. Steric exclusion chromatography coupled with refraction index was used to quantify VAL content, indicating uniform concentration in the filament after extrusion. Dissolution test in acidic media display over 80 % of VAL released within 20 to 25 min, reaching the Eur. Ph. Criteria of a rapid release. The outcomes of this study present suitable formulations to produce personalized dispersible form using HME with FDM 3D printing to treat pediatric epilepsy (1 month to 4 years old patients with dosage from 18 to 247 mg/kg/day) for the treatment of epilepsy.