3D printed capsules for colon targeted drug delivery

Abstract

Motivation: Local drug release within the colon holds great promise in the therapy of inflammatory bowel diseases. However, most approaches for specific colon targeting (e.g. pH or time dependent drug release) fail in vivo due to the complex gastrointestinal conditions (e.g. pH fluctuations or varying transit times). A promising approach is to use polymers that are degraded specifically by the colonic microbiota, such as guar gum. A capsule shell based on guar gum could provide a platform technology for colon targeted drug delivery. Since available technologies for capsule shell production are hardly suitable for handling of guar gum, we aimed at using 3D printing for the rapid prototyping of colon targeted capsules.

Materials and Methods: Filaments for FDM printing contained guar gum along with either HPMC or EUDRAGIT® RS. Capsule shells were printed with a commercially available FDM printer (Ultimaker 3, Ultimaker) and filled with a model drug. The drug release was tested in a conventional (BIOSTAT®, Sartorius) and in a custom-built bioreactor (MimiCol). The latter enabled us to simulate realistic pH fluctuations as they occur in the human colon. All tests were performed in Schaedler bouillon inoculated with microbiota derived from a human stool sample.

Results and Discussion: The 3D printing of guar gum capsules was successful. Investigations in the BIOSTAT® and MimiCol revealed an influence of the filament composition on the drug release behavior of the capsules. HPMC accelerated drug release whereas a distinct influence of the guar gum on drug release could not be observed. This was probably due to the absence of specific guar degrading bacteria in the microbiota.

Conclusion: 3D printing offers great advantages for development of novel drug delivery systems. The combination of innovative fabrication technologies and new in vitro test methods could significantly advance colon targeting.