The Chronotopic™ System for Pulsatile and Colonic Delivery of Active Molecules in the Era of Precision Medicine: Feasibility by 3D Printing via Fused Deposition Modeling (FDM)

The pulsatile-release Chronotopic™ system was conceived of as a drug-containing core surrounded by a coat made of swellable/soluble hydrophilic polymers, the latter being able to provide a programmable lag phase prior to drug liberation. This system was also proposed in a colon-targeting configuration, entailing a gastroresistant film to prevent early interaction of the inner coat with gastric fluids and enabling the attainment of a lag phase matching the small intestinal transit time.

Over the years, various multiple-step manufacturing processes have been tested for the fabrication of the Chronotopic™ system in both its configurations. This work focused on the evaluation of 3D printing by fused deposition modeling in view of its potential towards product personalization, on demand one-step manufacturing and efficient scale down of batches. The feasibility of each part of the Chronotopic™ system was independently investigated starting from in-house made filaments, characterizing the resulting specimens for physico-technological and performance characteristics.

The printing parameters identified as suitable during the set-up phase were then used to fabricate prototypes either in a single step for the pulsatile configuration or following two different fabrication approaches for the colon-targeting one.

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Materials

Hydroxypropyl cellulose, HPC (Klucel^® LF, Ashland, Kearny, NJ, USA); low viscosity hydroxypropyl cellulose, HPC SSL (Nisso HPC SSL, Nisso, Tokyo, Japan); methacrylic acid copolymer, EDR (Eudragit^® L 100-55, Evonik, Essen, Germany); polyvinyl alcohol, PVA (Gohsenol^® EG 03P, Mitsubishi Chemical, Tokyo, Japan); glycerol, GLY (Pharmagel, Milan, Italy); polyethylene glycol 400, PEG (Clariant Masterbatches, Milan, Italy); triethyl citrate, TEC (Sigma Aldrich, Milan, Italy); caffeine, CFF (ACEF, Milan, Italy); sodium starch glycolate, EXP (Explotab^® CLV, JRS Pharma, Rosenberg, Germany); high-amylose maize starch, AMY (Amylo^® N-460, Roquette Pharma, Lestrem, France); and polylactic acid filament (TreeD Filaments, Milan, Italy).

Article information: Melocchi, A.; Uboldi, M.; Briatico-Vangosa, F.; Moutaharrik, S.; Cerea, M.; Foppoli, A.; Maroni, A.; Palugan, L.; Zema, L.; Gazzaniga, A. The Chronotopic™ System for Pulsatile and Colonic Delivery of Active Molecules in the Era of Precision Medicine: Feasibility by 3D Printing via Fused Deposition Modeling (FDM). Pharmaceutics 2021, 13, 759. https://doi.org/10.3390/pharmaceutics13050759