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Oral tablets are a convenient form to deliver active pharmaceutical ingredients (API) and have a high level of acceptance from clinicians and patients. There is a wide range of excipients available for the fabrication of tablets thereby offering a versatile platform for the delivery of therapeutic agents to the gastrointestinal tract. However, the geometry of tablets is limited by conventional manufacturing processes. This study aimed to compare three manufacturing processes in the production of flat-faced oral tablets using the same formulation composed of a polymer blend and caffeine as a model drug: fused-filament fabrication (FFF), direct compression (DC) and injection molding (IM). Hot-melt extrusion was used to convert a powder blend into feedstock material for FFF and IM processes, while DC was performed on the powder mixture. Tablets were produced with the same dimensions and were characterized for their physical and dissolution properties. There were statistical differences in the physical properties and drug release profiles of the tablets produced by the different manufacturing processes. DC tablets displayed immediate release, IM provided sustained release over 48 h, and FFF tablets displayed both release types depending on the printing parameters. FFF continues to demonstrate high potential as a manufacturing process for the efficient production of personalized oral tablets.

The new frontier of medicine is the personalization of treatment to match a patient’s individual needs. Fused-filament fabrication (FFF) offers a platform for the personalization of drug dosage forms, but one of its chief shortcomings compared to other tablet production methods such as dry compression and wet granulation is relatively low throughput. Conversely, injection molding (IM) is a manufacturing technique for the high-volume production of parts, but in which individual part customization is both expensive and slow requiring the modification of expensive mold tooling. Mass-customization is the manufacture of custom products that match the needs of individual consumers but which are produced at the low unit cost associated with high-volume production. We successfully integrated for the first time FFF with IM in a multi-step manufacturing process for the production of custom bilayer tablets loaded with two active pharmaceutical ingredients used in the treatment of cardiovascular disease. The FFF layer was loaded with the diuretic hydrochlorothiazide, while the IM layer was loaded with lovastatin. Infill percentage was varied for the FFF layer as a means to modify drug release. The IM injection pressure was evaluated for its effect on drug release and layer-layer adhesion. The bilayer tablets obtained offered different combinations of drug release profiles, which were governed by a combination of factors, including surface area to volume ratio; IM injection volume penetration into the FFF layer; FFF infill percentage; layer tortuosity and porosity. These different parameters could be utilized to modify the individual release of both drugs from the bilayer tablet. Thus for the first time, we have demonstrated a viable method for the mass-customization of oral tablets which could hasten the rollout of personalized medicine. yes