(T1530-10-55) 3D Printed Container System for Delayed Release

Purpose: This study aimed to fabricate a programmed delayed release tablet, consisting of a core and two surrounding shells. The shells were constructed using fused deposition modeling 3D printing, while the core was produced by direct powder compression with microcrystalline cellulose and hydrocortisone as the active ingredient. The study leverages the capabilities of 3D printing to create complex geometries for programmed delayed release. The inner shell comprises HPMC 100 LV, PEO N80, and Soluplus, while the outer shell consists of ethyl cellulose, triethyl citrate, and HPC. The outer shell, permeable through fabricated holes, allows medium penetration into the inner shell, which swells and creates pressure for rupture. The time of rupture is hypothesized to depend on the rate of penetration and hydration of the inner layer, controlled by hole size, location, and shell thickness. The target is Addison's disease, characterized by cortisol insufficiency, requiring hydrocortisone tablets 2-3 times daily. This project aims to develop a delayed release hydrocortisone tablet to reduce daily dosing and improve treatment compliance.

Methods: The core tablet was produced by direct powder compression with a formulation of microcrystalline cellulose and hydrocortisone (90:10) and a total weight of 300 mg. Autodesk Tinkercad was used to design the container system as in the fig.1 . and the shells were produced using an Ultimaker S3 3D printer. The outer shell (ethyl cellulose: triethyl citrate: HPC) is permeable and rupturable, while the inner shell (HPMC 100LV: PEO N80: Soluplus) provides swelling as well as the required printability. The filaments for 3D printing were produced using ThermoFischer Process 11 hot melt extruder. The inner shell was produced with 0.4 mm walls, and the outer shell with 0.8 mm walls. The outer shell had 1 mm holes. Six variations were printed, altering the inner layer thickness and the number of holes in the outer layer as shown in the attached table and fig.1. Dissolution was performed in USP apparatus 2 using 900 mL of deionized water at 37.3°C and 100 RPM. The core tablet and six variations were tested to investigate the effect of top/bottom layer thickness and the number of holes on rupture and release time, analyzed using UV spectrophotometry at 248 nm.

Results: The Dimensions and weight of the tablets are listed in the attached table. The dissolution data is presented in the fig.2. The core tablets released the drug within 30 minutes. Out of the six variations, only one tablet experienced rupture and drug release. The others maintained structural integrity with no release over 24 hours.

Conclusion: This study represents the first step in fabricating a programmable timed rupture container system for delayed drug delivery. The study demonstrated a rupture mechanism based on double shells, penetration, and swelling within 24 hours. Further modifications, including altering the geometry and composition of the shells, are needed to enhance the system's programmability and effectiveness for personalized delayed release.

Fig.1: a) Digital Design of the Container System b) Cross-view of the 1 hole system c) Top-view of the 2 hole system d) Top-view of the 4 holes system e) Design no.6 system ruptured during dissolution d) Design no.6 System in dissolution at t=20.5 hrs.

Table: Tablet dimension, weight and designs for dissolution

Dissolution Profile