Insight into manufacturing of bespoke combination drug products containing carvedilol and simvastatin by fused deposition modelling.

Abstract

The goal of this study was to explore the fabrication of a combination drug product containing two poorly soluble active pharmaceutical ingredients (APIs), carvedilol (CAR) and simvastatin (SIM), in therapeutically relevant doses (25 mg of each API) with a distinct, easily distinguishable shape. Fused deposition modelling, combined with hot-melt extrusion (HME), was used to produce hollow heart-shaped dual-loaded tablets in which the two APIs were spatially separated with an intermediate API-free layer. Water-soluble hydroxypropyl methylcellulose of varying molecular weights was used as the primary polymer for HME. The incorporation of a processability-improving polymer, such as polycaprolactone, was necessary to facilitate the printing of these delicate geometries and lower the printing temperature. The 3D-printed tablets contained the therapeutic doses of both APIs; however, the further optimization of manufacturing processes is required to improve drug content uniformity. The drug release from the printed tablets was sustained, with complete release of CAR observed after 24 hours, demonstrating the suitability of the designed drug products for oral delivery.