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)

Abstract

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.

Connected healthcare: Improving patient care using digital health technologies

“…Although the American Society for Testing and Materials (ASTM) classifies seven main categories of 3D printing technologies [87], five main technologies have been researched within pharmaceuticals (e.g., binder jet printing [88,89,131,132]; fused deposition modelling, FDM [92,93,[133][134][135]; semi-solid extrusion, SSE [96,97,[136][137][138][139]; selective laser sintering (SLS) [99][100][101][102][103][104]; and vat photopolymerization [109,115,[140][141][142][143]). More recently, there has been a considerable interest in a sixth technology, termed direct powder extrusion (DPE) or melt extrusion deposition (MED™), which reduces risks of thermal drug degradation by simplifying the extrusion procedure into a single-step process [105][106][107]144].…”

Accelerating 3D printing of pharmaceutical products using machine learning

“…Specifically, the simplicity and low cost of FDM 3DP has led to the general view that it may be the technology to be clinically adopted to produce personalized medicines. Enthusiasm towards FDM 3DP amongst pharmaceutical researchers has been demonstrated by its use to manufacture a range of drug delivery devices, including 3D printed tablets (Printlets) ( Bogdahn et al, 2021 ; Figueiredo et al, 2022 ; Isreb et al, 2019 ; Melocchi et al, 2021 ; Oladeji et al, 2022 ; Pereira et al, 2020 ; Shi et al, 2021 ; Tranová et al, 2022 ; Windolf et al, 2022 ), gastro-retentive tablets ( Zhao et al, 2022 ), microneedles ( Wu et al, 2021 ), and patient-specific devices ( Arany et al, 2021 ; Carlier et al, 2021 ; Eleftheriadis and Fatouros, 2021 ; Eleftheriadis et al, 2020 ; Haddow et al, 2021 ; Liang et al, 2018 ; Saviano et al, 2022 ). While interest in pharmaceutical 3DP continues to grow, with pharmaceutical companies such as Aprecia and Triastek investing in the technology, progress is arguably hampered by the empirical process of formulation development ( Elbadawi et al, 2021b ; Seoane-Viaño et al, 2021 ).…”

Administration strategies and smart devices for drug release in specific sites of the upper GI tract

“…Several approaches have been pursued to enable their absorption upon oral intake, including coadministration with enzyme inhibitors, chemical modifications and formulation in polymeric microand nano-carriers [62,63]. Moreover, release into the colon was targeted [64][65][66][67][68][69][70][71]. Indeed, this region has broadly been described for the increased chances of absorption if compared with the small bowel, in view of the relatively long transit time, the lower concentration of proteolytic enzymes in the lumen, the brush-border membrane and the higher responsiveness of the mucosa to permeation enhancers.…”