3D printed tacrolimus suppositories for the treatment of ulcerative colitis

Abstract

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.

I Spy with My Little Eye: A Paediatric Visual Preferences Survey of 3D Printed Tablets

“…In FDM, thermoplastic filament is used as the feedstock material, made of a range of pharmaceutical grade excipients to fabricate various oral formulations [ 7 , 8 , 9 , 10 , 11 ]. Semi-solid extrusion (SSE), also known as gel extrusion, involves the extrusion of a gel or paste that rapidly solidifies, acting as a support for the next deposited layer [ 6 , 12 ]. Digital light processing (DLP) uses spatially controlled photopolymerization to create solid objects from a photoreactive liquid resin upon light irradiation and has been explored as a result of its high accuracy and superior resolution [ 13 , 14 ].…”

Suppositories with bioactive calcium phosphate nanoparticles for intestinal transfection and gene silencing

“…The delivery of drugs by suppositories has been extensively investigated (see Refs. [ 3,13 ] for reviews), including in situ gelling liquid suppositories, [ 14 ] 3D‐printed self‐supporting suppositories, [ 15 ] but only polymeric or liposomal nanoparticles have been applied so far. [ 16 ] Although a few reports exist on the delivery of nanoparticulate formulations by suppositories, [ 3,16,17 ] a suppository‐mediated gene transfer by nanoparticles has not yet been reported.…”

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

“…The mixture of lipid excipients and drug was selected from a previous study [25] where different combinations of lipid excipients were tested. The mixture composed of 79.55% of Gelucire 44/14, 19.55% of coconut oil and 0.9% of tacrolimus was mixed in a glass beaker and placed on a heating plate.…”

“…These suppositories are to be administered to small animals as rodents, so it is necessary to prepare them in an appropriate size and shape. To avoid the need for a mold specifically designed to meet these requirements, three-dimensional printing (3DP) technology can offer an alternative for the manufacture of small batches of suppositories, as demonstrated in a previous study were SSE was used to print human suppositories [25]. The implementation of 3DP in clinical practice allows one to personalize the dose to the patient's requirements, which ultimately leads to better outcomes for patients.…”