Tailored biopolymer capsules for colon-specific drug delivery: A 3D printing perspective

The present study aims to develop capsules employing hot melt extrusion (HME) and fused deposition modeling (FDM) three-dimensional (3D) printing approach. The primary objective was to establish a colon drug delivery system (CDDS) based on multiple release mechanisms. In the study, 3D printed hydroxypropylmethylcellulose (HPMC) based capsules containing polysaccharides (alginate, chitosan pectin from citrus and pectin from apple) were used to provide a time-triggered and microbiota-triggered release mechanism. Thirteen capsule compositions were tested, and physico-chemical properties, disintegration time, dissolution characteristic (lag time) and 50 days accelerated stability were assessed. In addition, an enteric coating by Eudragit S was tested to enhance protection against the gastric environment. Disintegration time of the capsule under in vivo conditions was verified in healthy volunteers by oral administration of the caffeine-loaded capsule and determination of the first-appearance time of caffeine in the saliva. Furthermore, in vivo monitoring of the transition time in piglets was performed by X-ray examination after oral administration of BaSO₄-loaded capsules. Optimal capsule composition was identified as HPMC and pectin from citrus in 80:20 wt% ratio. Printed capsules showed suitable physico-chemical properties, lag time and stability. Minimal drug release in the upper gastrointestinal tract (∼5 %) for the first 8-10 h was ensured by both coated and uncoated capsules. In addition, as demonstrated by the in vivo transition time monitoring assay, with accelerated passage of the capsule through the gastrointestinal tract, degradation is significantly accelerated (∼4 h) by a microbiota-triggered mechanism, effectively targeting the colon. Using 3D printing, a colonic-specific drug delivery system was prepared that could potentially be suitable for treating patients with various intestinal physiological conditions.