3D Printed Controlled-Release Budesonide Tablets and Comparative Evaluation of Release Behaviour in a Dynamic In Vitro Dissolution Model

Behaviour in a Dynamic In Vitro Dissolution Model A. Goyanes, H. Chang, A. Buanz, J. Wang, S. Gaisford, A. W. Basit University College London Purpose 3-dimensional printing (3DP) is a new technology which could potentially revolutionise the future of pharmaceutical manufacturing. In fused-deposition modelling (FDM) printing, a polymer filament is heated and extruded through a small tip and solidified on a build plate. FDM technology has the advantages of lower cost and the ability to fabricate personalised dosage forms using pharmaceuticalgrade polymers. Polyvinyl alcohol (PVA) filaments were loaded with budesonide by hot melt extrusion (HME) to manufacture 3D printed caplets with appropriate characteristics for fluid bed coating. In this study, various brands of budesonide products, in addition to the 3D printed/coated budesonide formulation, were tested and compared using a new bicarbonate buffer system under pH-dynamic dissolution conditions simulating the entire spectrum of gastrointestinal pH ranges. Methods A drug-loaded PVA filament was obtained by hot melt extrusion using a filaments extruder. A commercial PVA filament was cut into small pieces, milled in a grinder and mixed in a mortar and pestle with budesonide (5% w/w) until no agglomerated particles of drug or polymer were seen. The mixture of drug and PVA was then extruded using a singlescrew filament extruder, Noztec Pro hot melt extruder (temperature 180 °C, nozzle diameter 1.75 mm). The extruded filaments obtained were protected from light and kept in a vacuum desiccator until printing. The drug-loading of the filaments was determined by HPLC analysis. Caplets were fabricated with the drug-loaded filament in a standard fused-deposition modelling 3D printer, MakerBot Replicator 2X. The templates used to print the oral devices was designed with AutoCAD 2014 (Autodesk Inc., USA) and exported as a stereolithography file (.stl) into the 3D printer software (MakerBot Inc., USA). The selected 3D geometry was a size 4 capsule-shaped tablet, 14.30mm length x 5.30mm diameter. The 3D printed caplets were finally coated with a Eudragit L100 solution using a Strea-1 bottom spray fluidized bed coater (Aeromatic AG, Switzerland). Drug release from the 3DP tablets and the commercial formulations (Entocort and Uceris) was determined in a USP II apparatus (Pharmatest, Germany) simulating the environment conditions of the fasted GI tract. Briefly, the oral devices were placed for 2 h into 900 mL of 0.1M HCl to simulate gastric residence time, and subsequently into 950 mL of modified Hanks based dynamic physiological dissolution medium for 35 min (pH 5.6 to 7), which is converted by addition of 50mL of solution in 1000 mL of modified Krebs buffer (pH 7 to 7.4 and then to 6.5). The physiological buffers were pH controlled by an Auto pH system.