From 'fixed dose combinations' to 'a dynamic dose combiner': 3D printed bi-layer antihypertensive tablets

Abstract

There is an increased evidence for treating hypertension by a combination of two or more drugs. Increasing the number of daily intake of tablets has been reported to negatively affect the compliance by patients. Therefore, numerous fixed dose combinations (FDCs) have been introduced to the market. However, the inherent rigid nature of FDCs does not allow titration of the dose of each single component for individual patient needs. In this work, flexible dose combinations of two anti-hypertensive drugs in a single bilayer tablet with a range of doses were fabricated using dual fused deposition modelling (FDM) 3D printer. Enalapril maleate (EM) and hydrochlorothiazide (HCT) loaded filaments were produced via hot-melt extrusion (HME). Computer software was utilized to design sets of oval bi-layer tablet of individualised doses. Thermal analysis and x-ray diffractometer (XRD) indicated that HCT remained crystalline in the polymeric matrix whilst EM appeared to be in an amorphous form. The interaction between anionic EM and cationic methacrylate polymer may have contributed to a drop in the glass transition temperature (Tg) of the filament and obviated the need for a plasticiser. Across all tablet sets, the methacrylate polymeric matrix provided immediate drug release profiles. This dynamic dosing system maintained the advantages of FDCs while providing a superior flexibility of dosing range, hence offering an optimal clinical solution to hypertension therapy in a patient-centric healthcare service. [Abstract copyright: Copyright © 2018. Published by Elsevier B.V.]