A novel manufacturing technique for the production of tailored solid dosage forms

Abstract

The main objective of this study was to evaluate manufacturing processes for the fabrication of tailored solid dosage forms. Two hot-melt extrusion based manufacturing processes were investigated, a 3D printing process called fused filament fabrication (FFF) and the high-volume process injection moulding (IM). The initial hurdle to overcome was to determine the compatibility of pharmaceutical-grade materials with FFF, since the number of available feedstock materials is limited due to the novelty of this technology. Three material properties were identified as vital for determining the feasibility of a formulation to be implemented as feedstock for FFF. Melt flow rates over 10 g/10 min, brittleness equal or smaller than 2 %Pa (10^4), and a stiffness below 1,000 N/m are all crucial factors in whether a filament is flexible enough to be fed through the feeding mechanism at the same time being capable to act as a piston to push the molten material out of the nozzle in the hot-end of the extruder without breaking or bending. Our next step was to compare tablets fabricated via FFF to those produced via IM, a melt processing technique capable of continuous rapid manufacturing and direct compression (DC), a more conventional means to produce oral tablets in industry. Three parameters were varied during the 3D printing to evaluate their effects on the tablet properties. Infill percentage had the most significant effect on the release of the selected model drug, caffeine. IM samples were the slowest due to the increased tortuosity of the matrix, while DC offered the quickest release. IM offered the highest production rate and specific FFF parameters could be altered to control tablet properties. These two characteristics were combined for the production of a single bilayer tablet, thus combining the advantages of each manufacturing process while reducing the disadvantages, thus customising a tablet without significantly impeding production volume. This study proposes applying the methodology of mass-customisation to the production of solid dosage forms as technological platform to deliver patient-tailored solid dosage forms in a rapid, sustainable and affordable manner.