3D printing tablets for high-precision dose titration of caffeine

Through 3D printing (3DP), many parameters of solid oral dosage forms can be customised, allowing for truly personalised medicine in a way that traditional pharmaceutical manufacturing would struggle to achieve. One of the many options for customisation involves dose titration, allowing for gradual weaning of a medication at dose intervals smaller than what is available commercially. In this study we demonstrate the high accuracy and precision of 3DP dose titration of caffeine, selected due to its global prevalence as a behavioural drug and wellknown titration-dependent adverse reactions in humans. This was achieved using a simple filament base of polyvinyl alcohol, glycerol, and starch, utilising hot melt extrusion coupled with fused deposition modelling 3DP. Tablets containing 25 mg, 50 mg, and 100 mg doses of caffeine were successfully printed with drug content in the accepted range prescribed for conventional tablets (90 - 110%), and excellent precision whereby the weights of all doses showed a relative standard deviation of no more than 3%. Importantly, these results proved 3D printed tablets to be far superior to splitting a commercially available caffeine tablet. Additional assessment of filament and tablet samples were reviewed by differential scanning calorimetry, thermogravimetric analysis, HPLC, and scanning electron microscopy, showing no evidence of degradation of caffeine or the raw materials, with smooth and consistent filament extrusion. Upon dissolution, all tablets achieved greater than 70% release between 50 and 60 min, showing a predictable rapid release profile regardless of dose. The outcomes of this study highlight the benefits that dose titration with 3DP can offer, especially to more commonly prescribed medications that can have even more harmful withdrawal-induced adverse reactions.