3D printed tacrolimus suppositories for the treatment of ulcerative colitis

Ulcerative colitis is a global health problem, affecting millions of individuals worldwide. As an inflammatory condition localised in the large intestine, rectal delivery of immunosuppressive therapies such as tacrolimus is a promising strategy to maximise drug concentration at the site of action whilst minimising systemic side effects. Here, for the first time, self-supporting 3D-printed tacrolimus suppositories were prepared without the aid of moulds using a pharmaceutical semi-solid extrusion (SSE) 3D printer. The suppositories were printed vertically in three different sizes using combinations of two lipid pharmaceutical excipients (Gelucire 44/14 or Gelucire 48/16) and coconut oil. Although both suppository formulations had the appropriate viscosity characteristics for printing, the Gel 44 formulation required less energy and force for extrusion compared to the Gel 48 system. The Gel 44 disintegrated more rapidly but released tacrolimus more slowly than the Gel 48 suppositories. Although the tacrolimus release profiles were significantly different, both suppository systems released more than 80% drug within 120 min. DSC and XRD analysis was inconclusive in determining the solid-state properties of the drug in the suppositories. In summary, this article reports on the fabrication of 3D printed self-supporting suppositories to deliver personalised doses of a narrow therapeutic index drug, with potential benefits for patients with ulcerative colitis

3D Printed Tacrolimus Rectal Formulations Ameliorate Colitis in an Experimental Animal Model of Inflammatory Bowel Disease

The aim of this study was to fabricate novel self-supporting tacrolimus suppositories using semisolid extrusion 3-dimensional printing (3DP) and to investigate their efficacy in an experimental model of inflammatory bowel disease. Blends of Gelucire 44/14 and coconut oil were employed as lipid excipients to obtain suppository formulations with self-emulsifying properties, which were then tested in a TNBS (2,4,6-trinitrobenzenesulfonic acid) induced rat colitis model. Disease activity was monitored using PET/CT medical imaging; maximum standardized uptake values (SUVmax), a measure of tissue radiotracer accumulation rate, together with body weight changes and histological assessments, were used as inflammatory indices to monitor treatment efficacy. Following tacrolimus treatment, a significant reduction in SUVmax was observed on days 7 and 10 in the rat colon sections compared to non-treated animals. Histological analysis using Nancy index confirmed disease remission. Moreover, statistical analysis showed a positive correlation (R2 = 71.48%) between SUVmax values and weight changes over time. Overall, this study demonstrates the effectiveness of 3D printed tacrolimus suppositories to ameliorate colitis and highlights the utility of non-invasive PET/CT imaging to evaluate new therapies in the preclinical area