3D printing by fused deposition modeling (FDM) of a swellable/ erodible capsular device for oral pulsatile release of drugs Alice Melocchi a , Federico Parietti b , Giulia Loreti a , Alessandra Maroni a , Andrea Gazzaniga a, * , Lucia Zema a a Universit a degli Studi di Milano, Dipartimento di Scienze Farmaceutiche, Sezione di Tecnologia e Legislazione Farmaceutiche “M.E. Sangalli”, Via G. Colombo 71, 20133 Milan, Italy b Massachusetts Institute of Technology, Mechanical Engineering Department, 77 Massachusetts Ave, Cambridge, MA 02139, USA article info Article history: Received 19 May 2015 Received in revised form 23 July 2015 Accepted 24 July 2015 Available online xxx Keywords: 3D printing Fused deposition modeling Capsular device Pulsatile release Real-time prototyping Hydroxylpropyl cellulose filament abstract The aim of the present work was to explore the feasibility of fused deposition modeling (FDM) 3D printing in the manufacturing of capsular devices for oral pulsatile release based on a swellable/erodible polymer (hydroxypropyl cellulose, HPC). This involved an experimental evaluation of the possibility of fabricating hollow structures via FDM and the production of HPC filaments by hot melt extrusion (HME), which are not commercially available. Moreover, the set-up of appropriate computer aided design files had to be faced. A twin-screw extruder equipped with a rod-shaped die and a purposely designed pulling/calibrating device as well as a MakerBot Replicator 2 3D printer were employed for HME and FDM processing, respectively. Bodies and caps with satisfactory physico-technological properties were obtained. The release test of assembled capsular devices pointed out a lag phase before rapid and quantitative liberation of the drug. The morphological changes undergone by the device when in contact with water and their release performance turned out comparable with those of analogous systems fabricated by injection molding. The possibility of manufacturing capsular devices for oral pulsatile release by FDM 3D printing starting from HPC filaments purposely prepared was thus demonstrated, and the real-time prototyping potential of FDM was assessed. © 2015 Elsevier B.V. All rights reserved. 1. Introduction Oral drug delivery systems (DDSs) are aimed at improving the bioavailability of drug molecules or modifying the rate, time and/or site of their release [1e3]. Frequently, they are designed as drug cores coated with polymeric layers that are responsible for the control of release, thus acting as functional barriers. The latter may be enteric soluble films imparting gastro-resistance, erodible or rupturable layers delaying the onset of drug liberation or, alterna- tively, permeable ones prolonging release over the time span the drug takes to diffuse out of the system [4e8]. Recently, functional barriers in the form of capsular devices, i.e. functional containers, were successfully manufactured by injection molding (IM), which involves injecting thermoplastic materials into closed molds under appropriate temperature and pressure conditions [9]. This hot- processing technique is drawing increasing interest in the phar- maceutical field, chiefly in view of a reduction of production costs (e.g. no need for solvents, scalability, possibility of continuous manufacturing and patentability) and improvement of product characteristics (e.g. versatility, possibility of obtaining solid dis- persions/solutions of the active ingredient) [10]. Molded functional containers do represent a step forward in drug delivery as they would enable an independent development of the contents and the shell, thereby offering important benefits from both the regulatory and technical point of view, e.g. in terms of time-to-market and related costs. The molded shells could indeed be filled with differing drug formulations (e.g. powders, granules/pellets, semi- solids or liquids) and, importantly, govern drug release mainly based on the inherent design (morphology and thickness) and composition. Capsular devices for either enteric or pulsatile/time-dependent colonic release were obtained starting from hydroxypropyl meth- ylcellulose acetate succinate (HPMCAS) and hydroxypropyl * Corresponding author. E-mail addresses: alice.melocchi@unimi.it (A. Melocchi), parietti@mit.edu (F. Parietti), giulia.loreti@unimi.it (G. Loreti), alessandra.maroni@unimi.it (A. Maroni), andrea.gazzaniga@unimi.it (A. Gazzaniga), lucia.zema@unimi.it (L. Zema). Contents lists available at ScienceDirect Journal of Drug Delivery Science and Technology journal homepage: www.elsevier.com/locate/jddst http://dx.doi.org/10.1016/j.jddst.2015.07.016 1773-2247/© 2015 Elsevier B.V. All rights reserved. Journal of Drug Delivery Science and Technology xxx (2015) 1e8 Please cite this article in press as: A. Melocchi, et al., 3D printing by fused deposition modeling (FDM) of a swellable/erodible capsular device for oralpulsatile release of drugs, Journal of Drug Delivery Science and Technology (2015), http://dx.doi.org/10.1016/j.jddst.2015.07.016