RESUMEN
The robustness of 3D-printed mini-tablets as a platform to administer milligram dosages, intended for age-specific therapy, without the need of tablet splitting while maintaining similar release profiles, was investigated. Griseofulvin, as a model poorly water-soluble drug, and hydroxypropyl cellulose along with Kollicoat Protect as polymers were used to prepare filaments at 1-20% drug concentrations via hot-melt extrusion (HME). Higher drug concentrations served for testing the feasibility of a reduced number of mini-tablets to be administered. A reliable dose titration in the range 0.19-3.91 mg at a high accuracy (R2 of 0.999) was achieved through composite unit (multi-unit) mini-tablets. All mini-tablets produced had excellent content uniformity and their label claim values were within the acceptable range, proving that HME processing followed by 3D printing promotes content uniformity even for mini-tablets containing low drug doses (0.19 mg). Remarkably, the proposed approach allowed achieving similar drug release profiles via composite unit mini-tablets as well as single mini-tablets at high drug concentrations. In contrast, split tablets demonstrated different release behaviors, attributed to their size and shape differences. Overall, the distinct advantages of mini-tablets to provide dose flexibility while maintaining similar release profiles was demonstrated.
RESUMEN
The aim of this paper was to explore tablet design options for FDM 3D printing for simultaneous tailoring of drug release and dose. The drug, griseofulvin (GF), the polymer, hydroxypropyl cellulose (HPC), and processing temperatures were selected to avoid confounding effects arising from drug-polymer interactions. Filaments containing 0-30 wt% GF were prepared using a twin-screw extruder. Five tablet designs were printed using combinations of fixed or varying drug-concentration filaments, fixed or varying tablet sizes, or placebo and drug-rich regions. Two of five options met the main objective; varying drug-concentration filaments for fixed tablet size or printing fixed size duo-tablet having internal placebo regions of varying sizes. Analysis of the drug dissolution profiles revealed that the tablet surface area to volume (SA/V) ratio was the dominant factor, a higher SA/V ratio resulted in a faster release rate, mostly independent of the drug amount or its placement within the tablet. Use of HPC led to near zero-order release for most cases. For duo-tablets, long lag times proportional to placebo shell-thickness were observed. These results suggest that design options other than varying the tablet size would be needed to achieve desired drug release from FDM-based 3D printed personalized dosages.